Trial Outcomes & Findings for An Efficacy and Safety Study of Palovarotene for the Treatment of Fibrodysplasia Ossificans Progressiva. (NCT NCT03312634)

NCT ID: NCT03312634

Last Updated: 2023-11-29

Results Overview

The annualized new HO was assessed by low-dose, whole body computed tomography (WBCT), excluding head. The weighted linear mixed effect method without square-root transformation and negatives included was used for annualized new HO analysis.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 107 participants
• Primary outcome timeframe: Baseline (within one month of screening/Day 1) and up to 24 months
• Results posted on: 2023-11-29

Participant Flow

This Phase 3, open-label study conducted in adult and pediatric participants with fibrodysplasia ossificans progressiva (FOP) at 16 centers in 11 countries (Argentina, Australia, Brazil, Canada, France, Italy, Japan, Spain, Sweden, the United Kingdom, and the US) between 30 November 2017 and 07 September 2022.

This study included 3 parts: Part A, the main part of the study, Part B, the 24-month extension and Part C, up to 2 year post last dose of study treatment follow-up. A total of 107 participants were enrolled and treated in this study. Data from participants in PVO-1A-001 were used as an external control for only primary endpoint of this study. Hence, data for participants in PVO-1A-001 are reported in participant flow, baseline characteristics and adverse events section only.

Participant milestones

Measure	Palovarotene Participants were administered 5 milligram (mg) palovarotene orally once daily up to 48 months. Participants with flare-up symptoms or traumatic events received palovarotene 20 mg once daily for 4 weeks after the flare-up confirmation by the Investigator. Followed by palovarotene 10 mg once daily for 8 weeks.	Untreated (PVO-1A-001) Participants from study PVO-1A-001 (NCT02322255) were included with FOP caused by the R206H mutation and with baseline data. Participants were not administered palovarotene in this study and only compared as external control.
Overall Study STARTED	107	114
Overall Study COMPLETED	49	33
Overall Study NOT COMPLETED	58	81

Reasons for withdrawal

Measure	Palovarotene Participants were administered 5 milligram (mg) palovarotene orally once daily up to 48 months. Participants with flare-up symptoms or traumatic events received palovarotene 20 mg once daily for 4 weeks after the flare-up confirmation by the Investigator. Followed by palovarotene 10 mg once daily for 8 weeks.	Untreated (PVO-1A-001) Participants from study PVO-1A-001 (NCT02322255) were included with FOP caused by the R206H mutation and with baseline data. Participants were not administered palovarotene in this study and only compared as external control.
Overall Study Adverse Event	11	0
Overall Study Sponsor request	2	0
Overall Study Withdrawal by Subject	31	9
Overall Study Enrolled in an interventional study	0	52
Overall Study Enrolled in an interventional study at time of a flare-up	0	9
Overall Study Death	0	1
Overall Study Non-compliance	0	2
Overall Study Lost to Follow-up	0	1
Overall Study Enrolled into non-interventional study	0	5
Overall Study Worsening clinical condition	0	1
Overall Study Participant did not want to travel	0	1
Overall Study Physician Decision	1	0
Overall Study Other	13	0

Baseline Characteristics

An Efficacy and Safety Study of Palovarotene for the Treatment of Fibrodysplasia Ossificans Progressiva.

Baseline characteristics by cohort

Measure	Palovarotene n=99 Participants Participants were administered 5 mg palovarotene orally once daily up to 48 months. Participants with flare-up symptoms or traumatic events received palovarotene 20 mg once daily for 4 weeks after the flare-up confirmation by the Investigator. Followed by palovarotene 10 mg once daily for 8 weeks.	Untreated (PVO-1A-001) n=114 Participants Participants from study PVO-1A-001 (NCT02322255) were included with FOP caused by the R206H mutation and with baseline data. Participants were not administered palovarotene in this study and only compared as external control.	Total n=213 Participants Total of all reporting groups
Age, Categorical <=18 years	75 Participants n=5 Participants	70 Participants n=7 Participants	145 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	24 Participants n=5 Participants	44 Participants n=7 Participants	68 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Sex: Female, Male Female	46 Participants n=5 Participants	52 Participants n=7 Participants	98 Participants n=5 Participants
Sex: Female, Male Male	53 Participants n=5 Participants	62 Participants n=7 Participants	115 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	19 Participants n=5 Participants	23 Participants n=7 Participants	42 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	69 Participants n=5 Participants	73 Participants n=7 Participants	142 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	11 Participants n=5 Participants	18 Participants n=7 Participants	29 Participants n=5 Participants
Race/Ethnicity, Customized White	70 Participants n=5 Participants	84 Participants n=7 Participants	154 Participants n=5 Participants
Race/Ethnicity, Customized Black or African American	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized Asian	9 Participants n=5 Participants	8 Participants n=7 Participants	17 Participants n=5 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized Native Hawaiian or other Pacific Islander	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized Multiple	6 Participants n=5 Participants	2 Participants n=7 Participants	8 Participants n=5 Participants
Race/Ethnicity, Customized Other	1 Participants n=5 Participants	4 Participants n=7 Participants	5 Participants n=5 Participants
Race/Ethnicity, Customized Unknown	11 Participants n=5 Participants	15 Participants n=7 Participants	26 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline (within one month of screening/Day 1) and up to 24 months

Population: The Principal FAS includes all enrolled participants in the Principal EP who had a baseline HO volume measurement and at least 1 post-baseline HO volume measurement in study PVO-1A-301. For study PVO-1A-001, the Principal FAS included participants enrolled in study PVO-1A-001 with available baseline and at least 1 post-baseline HO volume measurement. Study PVO-1A-001 was used as an external control.

The annualized new HO was assessed by low-dose, whole body computed tomography (WBCT), excluding head. The weighted linear mixed effect method without square-root transformation and negatives included was used for annualized new HO analysis.

Outcome measures

Measure	Palovarotene n=97 Participants Participants were administered 5 mg palovarotene orally once daily up to 48 months. Participants with flare-up symptoms or traumatic events received palovarotene 20 mg once daily for 4 weeks after the flare-up confirmation by the Investigator. Followed by palovarotene 10 mg once daily for 8 weeks.	Untreated (PVO-1A-001) n=101 Participants Participants from study PVO-1A-001 (NCT02322255) were included with FOP caused by the R206H mutation and with baseline data. Participants were not administered palovarotene in this study and only compared as external control.
Annualized New Heterotopic Ossification (HO)	9427.1 cubic millimeters (mm^3) Standard Error 3084.0	23720.2 cubic millimeters (mm^3) Standard Error 4850.0

SECONDARY outcome

Timeframe: From Baseline (Day 1) up to end of 4-year follow-up period (approximately 57 months)

Population: The Principal FAS included all enrolled participants in the Principal EP who had a baseline HO volume measurement and at least 1 post-baseline HO volume measurement in study PVO-1A-301.

The new HO was assessed by WBCT scan. The percentage of participants with any new HO (volume > 0 mm^3) were analyzed using the Bayesian distribution. Results are presented for overall ITT period.

Outcome measures

Measure	Palovarotene n=97 Participants Participants were administered 5 mg palovarotene orally once daily up to 48 months. Participants with flare-up symptoms or traumatic events received palovarotene 20 mg once daily for 4 weeks after the flare-up confirmation by the Investigator. Followed by palovarotene 10 mg once daily for 8 weeks.	Untreated (PVO-1A-001) Participants from study PVO-1A-001 (NCT02322255) were included with FOP caused by the R206H mutation and with baseline data. Participants were not administered palovarotene in this study and only compared as external control.
Percentage of Participants With Any New HO	83.5 percentage of participants	—

SECONDARY outcome

Timeframe: From Baseline (Day 1) up to end of 4-year follow-up period (approximately 57 months)

Population: The Principal FAS included all enrolled participants in the Principal EP who had a baseline HO volume measurement and at least 1 post-baseline HO volume measurement in the study PVO-1A-301. Only data from the participants analyzed were reported.

All participants were analyzed for number of body regions with any new HO (new HO > 0 mm^3). The presence of HO across various body regions was analyzed using WBCT scan. Results are presented for overall ITT period

Outcome measures

Measure	Palovarotene n=81 Participants Participants were administered 5 mg palovarotene orally once daily up to 48 months. Participants with flare-up symptoms or traumatic events received palovarotene 20 mg once daily for 4 weeks after the flare-up confirmation by the Investigator. Followed by palovarotene 10 mg once daily for 8 weeks.	Untreated (PVO-1A-001) Participants from study PVO-1A-001 (NCT02322255) were included with FOP caused by the R206H mutation and with baseline data. Participants were not administered palovarotene in this study and only compared as external control.
Number of Body Regions With New HO	3.0 body regions Standard Deviation 1.68	—

SECONDARY outcome

Timeframe: Month 12

Population: The Principal SS included all enrolled participants in the Principal EP set (ie, participants with the R206H ACVR1 mutation) receiving at least 1 dose of palovarotene in study PVO-1A-301. Only data from the participants analyzed at Month 12 reported.

Flare-up as an event with one or more flare-up symptoms, and regardless of flare-up symptom onset. Flare-up was evaluated remotely, or by telephone or video-conferencing, unless the Investigator deemed that a site visit was necessary.

Outcome measures

Measure	Palovarotene n=99 Participants Participants were administered 5 mg palovarotene orally once daily up to 48 months. Participants with flare-up symptoms or traumatic events received palovarotene 20 mg once daily for 4 weeks after the flare-up confirmation by the Investigator. Followed by palovarotene 10 mg once daily for 8 weeks.	Untreated (PVO-1A-001) Participants from study PVO-1A-001 (NCT02322255) were included with FOP caused by the R206H mutation and with baseline data. Participants were not administered palovarotene in this study and only compared as external control.
Percentage of Participants With Flare-Ups	64.6 percentage of participants	—

SECONDARY outcome

Timeframe: From Baseline (Day 1) up to end of 4-year follow-up period (approximately 57 months)

Population: The Safety analysis set included all enrolled participants who received at least 1 dose of palovarotene in study PVO-1A-301.

Flare-up as an event with one or more flare-up symptoms, and regardless of flare-up symptom onset. Flare-up was evaluated remotely, or by telephone or video-conferencing, unless the Investigator deemed that a site visit was necessary. The flare-up rate per participant-month exposure was analyzed using a negative binomial regression. Results are presented for overall ITT period.

Outcome measures

Measure	Palovarotene n=107 Participants Participants were administered 5 mg palovarotene orally once daily up to 48 months. Participants with flare-up symptoms or traumatic events received palovarotene 20 mg once daily for 4 weeks after the flare-up confirmation by the Investigator. Followed by palovarotene 10 mg once daily for 8 weeks.	Untreated (PVO-1A-001) Participants from study PVO-1A-001 (NCT02322255) were included with FOP caused by the R206H mutation and with baseline data. Participants were not administered palovarotene in this study and only compared as external control.
Ratio of Flare-Up Per Participant-Month of Exposure	0.2 ratio of flare-up Standard Deviation 0.40	—

Adverse Events

Palovarotene 5 mg

Serious events: 34 serious events

Other events: 105 other events

Deaths: 0 deaths

Palovarotene 20/10 mg

Serious events: 19 serious events

Other events: 77 other events

Deaths: 0 deaths

Untreated (PVO-1A-001)

Serious events: 0 serious events

Other events: 0 other events

Deaths: 1 deaths

Serious adverse events

Measure	Palovarotene 5 mg n=107 participants at risk Participants were administered 5 mg palovarotene orally once daily up to 48 months.	Palovarotene 20/10 mg n=81 participants at risk Participants with flare-up symptoms or traumatic events received palovarotene 20 mg once daily for 4 weeks after the flare-up confirmation by the Investigator. Followed by palovarotene 10 mg once daily for 8 weeks.	Untreated (PVO-1A-001) n=114 participants at risk Participants from study PVO-1A-001 (NCT02322255) were included with FOP caused by the R206H mutation and with baseline data. Participants were not administered palovarotene in this study and only compared as external control. While no pharmacological intervention was applied in this observational study, safety issues resulting only from any study-related procedure were recorded as AEs.
Musculoskeletal and connective tissue disorders Epiphyses Premature Fusion	10.3% 11/107 • Number of events 11 • Treatment-emergent adverse events are collected from first date of palovarotene intake up to end of 4-year follow-up period (approximately 57 months) for study PVO-1A-301. For study PVO-1A-001, adverse events (AEs) were collected from study day 1 up to approximately 37 months. While no pharmacological intervention was applied in this observational study (PVO-1A-001), safety issues resulting only from any study-related procedure were recorded as AEs. MedDRA version 21.0 for PVO-1A-001 study. The Safety analysis set included all enrolled participants who received at least 1 dose of palovarotene in study PVO-1A-301. The FAS included all participants in the Enrolled Analysis Set with FOP caused by the R206H mutation and who had baseline data in study PVO-1A-001.	12.3% 10/81 • Number of events 10 • Treatment-emergent adverse events are collected from first date of palovarotene intake up to end of 4-year follow-up period (approximately 57 months) for study PVO-1A-301. For study PVO-1A-001, adverse events (AEs) were collected from study day 1 up to approximately 37 months. While no pharmacological intervention was applied in this observational study (PVO-1A-001), safety issues resulting only from any study-related procedure were recorded as AEs. MedDRA version 21.0 for PVO-1A-001 study. The Safety analysis set included all enrolled participants who received at least 1 dose of palovarotene in study PVO-1A-301. The FAS included all participants in the Enrolled Analysis Set with FOP caused by the R206H mutation and who had baseline data in study PVO-1A-001.	0.00% 0/114 • Treatment-emergent adverse events are collected from first date of palovarotene intake up to end of 4-year follow-up period (approximately 57 months) for study PVO-1A-301. For study PVO-1A-001, adverse events (AEs) were collected from study day 1 up to approximately 37 months. While no pharmacological intervention was applied in this observational study (PVO-1A-001), safety issues resulting only from any study-related procedure were recorded as AEs. MedDRA version 21.0 for PVO-1A-001 study. The Safety analysis set included all enrolled participants who received at least 1 dose of palovarotene in study PVO-1A-301. The FAS included all participants in the Enrolled Analysis Set with FOP caused by the R206H mutation and who had baseline data in study PVO-1A-001.
Musculoskeletal and connective tissue disorders Back Pain	0.00% 0/107 • Treatment-emergent adverse events are collected from first date of palovarotene intake up to end of 4-year follow-up period (approximately 57 months) for study PVO-1A-301. For study PVO-1A-001, adverse events (AEs) were collected from study day 1 up to approximately 37 months. While no pharmacological intervention was applied in this observational study (PVO-1A-001), safety issues resulting only from any study-related procedure were recorded as AEs. MedDRA version 21.0 for PVO-1A-001 study. The Safety analysis set included all enrolled participants who received at least 1 dose of palovarotene in study PVO-1A-301. The FAS included all participants in the Enrolled Analysis Set with FOP caused by the R206H mutation and who had baseline data in study PVO-1A-001.	1.2% 1/81 • Number of events 1 • Treatment-emergent adverse events are collected from first date of palovarotene intake up to end of 4-year follow-up period (approximately 57 months) for study PVO-1A-301. For study PVO-1A-001, adverse events (AEs) were collected from study day 1 up to approximately 37 months. While no pharmacological intervention was applied in this observational study (PVO-1A-001), safety issues resulting only from any study-related procedure were recorded as AEs. MedDRA version 21.0 for PVO-1A-001 study. The Safety analysis set included all enrolled participants who received at least 1 dose of palovarotene in study PVO-1A-301. The FAS included all participants in the Enrolled Analysis Set with FOP caused by the R206H mutation and who had baseline data in study PVO-1A-001.	0.00% 0/114 • Treatment-emergent adverse events are collected from first date of palovarotene intake up to end of 4-year follow-up period (approximately 57 months) for study PVO-1A-301. For study PVO-1A-001, adverse events (AEs) were collected from study day 1 up to approximately 37 months. While no pharmacological intervention was applied in this observational study (PVO-1A-001), safety issues resulting only from any study-related procedure were recorded as AEs. MedDRA version 21.0 for PVO-1A-001 study. The Safety analysis set included all enrolled participants who received at least 1 dose of palovarotene in study PVO-1A-301. The FAS included all participants in the Enrolled Analysis Set with FOP caused by the R206H mutation and who had baseline data in study PVO-1A-001.
Musculoskeletal and connective tissue disorders Epiphyseal Disorder	0.93% 1/107 • Number of events 1 • Treatment-emergent adverse events are collected from first date of palovarotene intake up to end of 4-year follow-up period (approximately 57 months) for study PVO-1A-301. For study PVO-1A-001, adverse events (AEs) were collected from study day 1 up to approximately 37 months. While no pharmacological intervention was applied in this observational study (PVO-1A-001), safety issues resulting only from any study-related procedure were recorded as AEs. MedDRA version 21.0 for PVO-1A-001 study. The Safety analysis set included all enrolled participants who received at least 1 dose of palovarotene in study PVO-1A-301. The FAS included all participants in the Enrolled Analysis Set with FOP caused by the R206H mutation and who had baseline data in study PVO-1A-001.	0.00% 0/81 • Treatment-emergent adverse events are collected from first date of palovarotene intake up to end of 4-year follow-up period (approximately 57 months) for study PVO-1A-301. For study PVO-1A-001, adverse events (AEs) were collected from study day 1 up to approximately 37 months. While no pharmacological intervention was applied in this observational study (PVO-1A-001), safety issues resulting only from any study-related procedure were recorded as AEs. MedDRA version 21.0 for PVO-1A-001 study. The Safety analysis set included all enrolled participants who received at least 1 dose of palovarotene in study PVO-1A-301. The FAS included all participants in the Enrolled Analysis Set with FOP caused by the R206H mutation and who had baseline data in study PVO-1A-001.	0.00% 0/114 • Treatment-emergent adverse events are collected from first date of palovarotene intake up to end of 4-year follow-up period (approximately 57 months) for study PVO-1A-301. For study PVO-1A-001, adverse events (AEs) were collected from study day 1 up to approximately 37 months. While no pharmacological intervention was applied in this observational study (PVO-1A-001), safety issues resulting only from any study-related procedure were recorded as AEs. MedDRA version 21.0 for PVO-1A-001 study. The Safety analysis set included all enrolled participants who received at least 1 dose of palovarotene in study PVO-1A-301. The FAS included all participants in the Enrolled Analysis Set with FOP caused by the R206H mutation and who had baseline data in study PVO-1A-001.
Musculoskeletal and connective tissue disorders Mobility Decreased	0.00% 0/107 • Treatment-emergent adverse events are collected from first date of palovarotene intake up to end of 4-year follow-up period (approximately 57 months) for study PVO-1A-301. For study PVO-1A-001, adverse events (AEs) were collected from study day 1 up to approximately 37 months. While no pharmacological intervention was applied in this observational study (PVO-1A-001), safety issues resulting only from any study-related procedure were recorded as AEs. MedDRA version 21.0 for PVO-1A-001 study. The Safety analysis set included all enrolled participants who received at least 1 dose of palovarotene in study PVO-1A-301. The FAS included all participants in the Enrolled Analysis Set with FOP caused by the R206H mutation and who had baseline data in study PVO-1A-001.	1.2% 1/81 • Number of events 1 • Treatment-emergent adverse events are collected from first date of palovarotene intake up to end of 4-year follow-up period (approximately 57 months) for study PVO-1A-301. For study PVO-1A-001, adverse events (AEs) were collected from study day 1 up to approximately 37 months. While no pharmacological intervention was applied in this observational study (PVO-1A-001), safety issues resulting only from any study-related procedure were recorded as AEs. MedDRA version 21.0 for PVO-1A-001 study. The Safety analysis set included all enrolled participants who received at least 1 dose of palovarotene in study PVO-1A-301. The FAS included all participants in the Enrolled Analysis Set with FOP caused by the R206H mutation and who had baseline data in study PVO-1A-001.	0.00% 0/114 • Treatment-emergent adverse events are collected from first date of palovarotene intake up to end of 4-year follow-up period (approximately 57 months) for study PVO-1A-301. For study PVO-1A-001, adverse events (AEs) were collected from study day 1 up to approximately 37 months. While no pharmacological intervention was applied in this observational study (PVO-1A-001), safety issues resulting only from any study-related procedure were recorded as AEs. MedDRA version 21.0 for PVO-1A-001 study. The Safety analysis set included all enrolled participants who received at least 1 dose of palovarotene in study PVO-1A-301. The FAS included all participants in the Enrolled Analysis Set with FOP caused by the R206H mutation and who had baseline data in study PVO-1A-001.
Infections and infestations Appendicitis	0.93% 1/107 • Number of events 1 • Treatment-emergent adverse events are collected from first date of palovarotene intake up to end of 4-year follow-up period (approximately 57 months) for study PVO-1A-301. For study PVO-1A-001, adverse events (AEs) were collected from study day 1 up to approximately 37 months. While no pharmacological intervention was applied in this observational study (PVO-1A-001), safety issues resulting only from any study-related procedure were recorded as AEs. MedDRA version 21.0 for PVO-1A-001 study. The Safety analysis set included all enrolled participants who received at least 1 dose of palovarotene in study PVO-1A-301. The FAS included all participants in the Enrolled Analysis Set with FOP caused by the R206H mutation and who had baseline data in study PVO-1A-001.	0.00% 0/81 • Treatment-emergent adverse events are collected from first date of palovarotene intake up to end of 4-year follow-up period (approximately 57 months) for study PVO-1A-301. For study PVO-1A-001, adverse events (AEs) were collected from study day 1 up to approximately 37 months. While no pharmacological intervention was applied in this observational study (PVO-1A-001), safety issues resulting only from any study-related procedure were recorded as AEs. MedDRA version 21.0 for PVO-1A-001 study. The Safety analysis set included all enrolled participants who received at least 1 dose of palovarotene in study PVO-1A-301. The FAS included all participants in the Enrolled Analysis Set with FOP caused by the R206H mutation and who had baseline data in study PVO-1A-001.	0.00% 0/114 • Treatment-emergent adverse events are collected from first date of palovarotene intake up to end of 4-year follow-up period (approximately 57 months) for study PVO-1A-301. For study PVO-1A-001, adverse events (AEs) were collected from study day 1 up to approximately 37 months. While no pharmacological intervention was applied in this observational study (PVO-1A-001), safety issues resulting only from any study-related procedure were recorded as AEs. MedDRA version 21.0 for PVO-1A-001 study. The Safety analysis set included all enrolled participants who received at least 1 dose of palovarotene in study PVO-1A-301. The FAS included all participants in the Enrolled Analysis Set with FOP caused by the R206H mutation and who had baseline data in study PVO-1A-001.
Infections and infestations Bacterial Sepsis	0.93% 1/107 • Number of events 1 • Treatment-emergent adverse events are collected from first date of palovarotene intake up to end of 4-year follow-up period (approximately 57 months) for study PVO-1A-301. For study PVO-1A-001, adverse events (AEs) were collected from study day 1 up to approximately 37 months. While no pharmacological intervention was applied in this observational study (PVO-1A-001), safety issues resulting only from any study-related procedure were recorded as AEs. MedDRA version 21.0 for PVO-1A-001 study. The Safety analysis set included all enrolled participants who received at least 1 dose of palovarotene in study PVO-1A-301. The FAS included all participants in the Enrolled Analysis Set with FOP caused by the R206H mutation and who had baseline data in study PVO-1A-001.	0.00% 0/81 • Treatment-emergent adverse events are collected from first date of palovarotene intake up to end of 4-year follow-up period (approximately 57 months) for study PVO-1A-301. For study PVO-1A-001, adverse events (AEs) were collected from study day 1 up to approximately 37 months. While no pharmacological intervention was applied in this observational study (PVO-1A-001), safety issues resulting only from any study-related procedure were recorded as AEs. MedDRA version 21.0 for PVO-1A-001 study. The Safety analysis set included all enrolled participants who received at least 1 dose of palovarotene in study PVO-1A-301. The FAS included all participants in the Enrolled Analysis Set with FOP caused by the R206H mutation and who had baseline data in study PVO-1A-001.	0.00% 0/114 • Treatment-emergent adverse events are collected from first date of palovarotene intake up to end of 4-year follow-up period (approximately 57 months) for study PVO-1A-301. For study PVO-1A-001, adverse events (AEs) were collected from study day 1 up to approximately 37 months. While no pharmacological intervention was applied in this observational study (PVO-1A-001), safety issues resulting only from any study-related procedure were recorded as AEs. MedDRA version 21.0 for PVO-1A-001 study. The Safety analysis set included all enrolled participants who received at least 1 dose of palovarotene in study PVO-1A-301. The FAS included all participants in the Enrolled Analysis Set with FOP caused by the R206H mutation and who had baseline data in study PVO-1A-001.
Infections and infestations Cellulitis	0.00% 0/107 • Treatment-emergent adverse events are collected from first date of palovarotene intake up to end of 4-year follow-up period (approximately 57 months) for study PVO-1A-301. For study PVO-1A-001, adverse events (AEs) were collected from study day 1 up to approximately 37 months. While no pharmacological intervention was applied in this observational study (PVO-1A-001), safety issues resulting only from any study-related procedure were recorded as AEs. MedDRA version 21.0 for PVO-1A-001 study. The Safety analysis set included all enrolled participants who received at least 1 dose of palovarotene in study PVO-1A-301. The FAS included all participants in the Enrolled Analysis Set with FOP caused by the R206H mutation and who had baseline data in study PVO-1A-001.	1.2% 1/81 • Number of events 1 • Treatment-emergent adverse events are collected from first date of palovarotene intake up to end of 4-year follow-up period (approximately 57 months) for study PVO-1A-301. For study PVO-1A-001, adverse events (AEs) were collected from study day 1 up to approximately 37 months. While no pharmacological intervention was applied in this observational study (PVO-1A-001), safety issues resulting only from any study-related procedure were recorded as AEs. MedDRA version 21.0 for PVO-1A-001 study. The Safety analysis set included all enrolled participants who received at least 1 dose of palovarotene in study PVO-1A-301. The FAS included all participants in the Enrolled Analysis Set with FOP caused by the R206H mutation and who had baseline data in study PVO-1A-001.	0.00% 0/114 • Treatment-emergent adverse events are collected from first date of palovarotene intake up to end of 4-year follow-up period (approximately 57 months) for study PVO-1A-301. For study PVO-1A-001, adverse events (AEs) were collected from study day 1 up to approximately 37 months. While no pharmacological intervention was applied in this observational study (PVO-1A-001), safety issues resulting only from any study-related procedure were recorded as AEs. MedDRA version 21.0 for PVO-1A-001 study. The Safety analysis set included all enrolled participants who received at least 1 dose of palovarotene in study PVO-1A-301. The FAS included all participants in the Enrolled Analysis Set with FOP caused by the R206H mutation and who had baseline data in study PVO-1A-001.
Infections and infestations Escherichia Sepsis	0.00% 0/107 • Treatment-emergent adverse events are collected from first date of palovarotene intake up to end of 4-year follow-up period (approximately 57 months) for study PVO-1A-301. For study PVO-1A-001, adverse events (AEs) were collected from study day 1 up to approximately 37 months. While no pharmacological intervention was applied in this observational study (PVO-1A-001), safety issues resulting only from any study-related procedure were recorded as AEs. MedDRA version 21.0 for PVO-1A-001 study. The Safety analysis set included all enrolled participants who received at least 1 dose of palovarotene in study PVO-1A-301. The FAS included all participants in the Enrolled Analysis Set with FOP caused by the R206H mutation and who had baseline data in study PVO-1A-001.	1.2% 1/81 • Number of events 1 • Treatment-emergent adverse events are collected from first date of palovarotene intake up to end of 4-year follow-up period (approximately 57 months) for study PVO-1A-301. For study PVO-1A-001, adverse events (AEs) were collected from study day 1 up to approximately 37 months. While no pharmacological intervention was applied in this observational study (PVO-1A-001), safety issues resulting only from any study-related procedure were recorded as AEs. MedDRA version 21.0 for PVO-1A-001 study. The Safety analysis set included all enrolled participants who received at least 1 dose of palovarotene in study PVO-1A-301. The FAS included all participants in the Enrolled Analysis Set with FOP caused by the R206H mutation and who had baseline data in study PVO-1A-001.	0.00% 0/114 • Treatment-emergent adverse events are collected from first date of palovarotene intake up to end of 4-year follow-up period (approximately 57 months) for study PVO-1A-301. For study PVO-1A-001, adverse events (AEs) were collected from study day 1 up to approximately 37 months. While no pharmacological intervention was applied in this observational study (PVO-1A-001), safety issues resulting only from any study-related procedure were recorded as AEs. MedDRA version 21.0 for PVO-1A-001 study. The Safety analysis set included all enrolled participants who received at least 1 dose of palovarotene in study PVO-1A-301. The FAS included all participants in the Enrolled Analysis Set with FOP caused by the R206H mutation and who had baseline data in study PVO-1A-001.
Infections and infestations Klebsiella Bacteremia	0.93% 1/107 • Number of events 1 • Treatment-emergent adverse events are collected from first date of palovarotene intake up to end of 4-year follow-up period (approximately 57 months) for study PVO-1A-301. For study PVO-1A-001, adverse events (AEs) were collected from study day 1 up to approximately 37 months. While no pharmacological intervention was applied in this observational study (PVO-1A-001), safety issues resulting only from any study-related procedure were recorded as AEs. MedDRA version 21.0 for PVO-1A-001 study. The Safety analysis set included all enrolled participants who received at least 1 dose of palovarotene in study PVO-1A-301. The FAS included all participants in the Enrolled Analysis Set with FOP caused by the R206H mutation and who had baseline data in study PVO-1A-001.	0.00% 0/81 • Treatment-emergent adverse events are collected from first date of palovarotene intake up to end of 4-year follow-up period (approximately 57 months) for study PVO-1A-301. For study PVO-1A-001, adverse events (AEs) were collected from study day 1 up to approximately 37 months. While no pharmacological intervention was applied in this observational study (PVO-1A-001), safety issues resulting only from any study-related procedure were recorded as AEs. MedDRA version 21.0 for PVO-1A-001 study. The Safety analysis set included all enrolled participants who received at least 1 dose of palovarotene in study PVO-1A-301. The FAS included all participants in the Enrolled Analysis Set with FOP caused by the R206H mutation and who had baseline data in study PVO-1A-001.	0.00% 0/114 • Treatment-emergent adverse events are collected from first date of palovarotene intake up to end of 4-year follow-up period (approximately 57 months) for study PVO-1A-301. For study PVO-1A-001, adverse events (AEs) were collected from study day 1 up to approximately 37 months. While no pharmacological intervention was applied in this observational study (PVO-1A-001), safety issues resulting only from any study-related procedure were recorded as AEs. MedDRA version 21.0 for PVO-1A-001 study. The Safety analysis set included all enrolled participants who received at least 1 dose of palovarotene in study PVO-1A-301. The FAS included all participants in the Enrolled Analysis Set with FOP caused by the R206H mutation and who had baseline data in study PVO-1A-001.
Infections and infestations Mycoplasma Infection	0.00% 0/107 • Treatment-emergent adverse events are collected from first date of palovarotene intake up to end of 4-year follow-up period (approximately 57 months) for study PVO-1A-301. For study PVO-1A-001, adverse events (AEs) were collected from study day 1 up to approximately 37 months. While no pharmacological intervention was applied in this observational study (PVO-1A-001), safety issues resulting only from any study-related procedure were recorded as AEs. MedDRA version 21.0 for PVO-1A-001 study. The Safety analysis set included all enrolled participants who received at least 1 dose of palovarotene in study PVO-1A-301. The FAS included all participants in the Enrolled Analysis Set with FOP caused by the R206H mutation and who had baseline data in study PVO-1A-001.	1.2% 1/81 • Number of events 1 • Treatment-emergent adverse events are collected from first date of palovarotene intake up to end of 4-year follow-up period (approximately 57 months) for study PVO-1A-301. For study PVO-1A-001, adverse events (AEs) were collected from study day 1 up to approximately 37 months. While no pharmacological intervention was applied in this observational study (PVO-1A-001), safety issues resulting only from any study-related procedure were recorded as AEs. MedDRA version 21.0 for PVO-1A-001 study. The Safety analysis set included all enrolled participants who received at least 1 dose of palovarotene in study PVO-1A-301. The FAS included all participants in the Enrolled Analysis Set with FOP caused by the R206H mutation and who had baseline data in study PVO-1A-001.	0.00% 0/114 • Treatment-emergent adverse events are collected from first date of palovarotene intake up to end of 4-year follow-up period (approximately 57 months) for study PVO-1A-301. For study PVO-1A-001, adverse events (AEs) were collected from study day 1 up to approximately 37 months. While no pharmacological intervention was applied in this observational study (PVO-1A-001), safety issues resulting only from any study-related procedure were recorded as AEs. MedDRA version 21.0 for PVO-1A-001 study. The Safety analysis set included all enrolled participants who received at least 1 dose of palovarotene in study PVO-1A-301. The FAS included all participants in the Enrolled Analysis Set with FOP caused by the R206H mutation and who had baseline data in study PVO-1A-001.
Infections and infestations Pneumonia	0.93% 1/107 • Number of events 1 • Treatment-emergent adverse events are collected from first date of palovarotene intake up to end of 4-year follow-up period (approximately 57 months) for study PVO-1A-301. For study PVO-1A-001, adverse events (AEs) were collected from study day 1 up to approximately 37 months. While no pharmacological intervention was applied in this observational study (PVO-1A-001), safety issues resulting only from any study-related procedure were recorded as AEs. MedDRA version 21.0 for PVO-1A-001 study. The Safety analysis set included all enrolled participants who received at least 1 dose of palovarotene in study PVO-1A-301. The FAS included all participants in the Enrolled Analysis Set with FOP caused by the R206H mutation and who had baseline data in study PVO-1A-001.	1.2% 1/81 • Number of events 1 • Treatment-emergent adverse events are collected from first date of palovarotene intake up to end of 4-year follow-up period (approximately 57 months) for study PVO-1A-301. For study PVO-1A-001, adverse events (AEs) were collected from study day 1 up to approximately 37 months. While no pharmacological intervention was applied in this observational study (PVO-1A-001), safety issues resulting only from any study-related procedure were recorded as AEs. MedDRA version 21.0 for PVO-1A-001 study. The Safety analysis set included all enrolled participants who received at least 1 dose of palovarotene in study PVO-1A-301. The FAS included all participants in the Enrolled Analysis Set with FOP caused by the R206H mutation and who had baseline data in study PVO-1A-001.	0.00% 0/114 • Treatment-emergent adverse events are collected from first date of palovarotene intake up to end of 4-year follow-up period (approximately 57 months) for study PVO-1A-301. For study PVO-1A-001, adverse events (AEs) were collected from study day 1 up to approximately 37 months. While no pharmacological intervention was applied in this observational study (PVO-1A-001), safety issues resulting only from any study-related procedure were recorded as AEs. MedDRA version 21.0 for PVO-1A-001 study. The Safety analysis set included all enrolled participants who received at least 1 dose of palovarotene in study PVO-1A-301. The FAS included all participants in the Enrolled Analysis Set with FOP caused by the R206H mutation and who had baseline data in study PVO-1A-001.
Infections and infestations Urosepsis	0.00% 0/107 • Treatment-emergent adverse events are collected from first date of palovarotene intake up to end of 4-year follow-up period (approximately 57 months) for study PVO-1A-301. For study PVO-1A-001, adverse events (AEs) were collected from study day 1 up to approximately 37 months. While no pharmacological intervention was applied in this observational study (PVO-1A-001), safety issues resulting only from any study-related procedure were recorded as AEs. MedDRA version 21.0 for PVO-1A-001 study. The Safety analysis set included all enrolled participants who received at least 1 dose of palovarotene in study PVO-1A-301. The FAS included all participants in the Enrolled Analysis Set with FOP caused by the R206H mutation and who had baseline data in study PVO-1A-001.	1.2% 1/81 • Number of events 1 • Treatment-emergent adverse events are collected from first date of palovarotene intake up to end of 4-year follow-up period (approximately 57 months) for study PVO-1A-301. For study PVO-1A-001, adverse events (AEs) were collected from study day 1 up to approximately 37 months. While no pharmacological intervention was applied in this observational study (PVO-1A-001), safety issues resulting only from any study-related procedure were recorded as AEs. MedDRA version 21.0 for PVO-1A-001 study. The Safety analysis set included all enrolled participants who received at least 1 dose of palovarotene in study PVO-1A-301. The FAS included all participants in the Enrolled Analysis Set with FOP caused by the R206H mutation and who had baseline data in study PVO-1A-001.	0.00% 0/114 • Treatment-emergent adverse events are collected from first date of palovarotene intake up to end of 4-year follow-up period (approximately 57 months) for study PVO-1A-301. For study PVO-1A-001, adverse events (AEs) were collected from study day 1 up to approximately 37 months. While no pharmacological intervention was applied in this observational study (PVO-1A-001), safety issues resulting only from any study-related procedure were recorded as AEs. MedDRA version 21.0 for PVO-1A-001 study. The Safety analysis set included all enrolled participants who received at least 1 dose of palovarotene in study PVO-1A-301. The FAS included all participants in the Enrolled Analysis Set with FOP caused by the R206H mutation and who had baseline data in study PVO-1A-001.
General disorders Condition Aggravated	1.9% 2/107 • Number of events 2 • Treatment-emergent adverse events are collected from first date of palovarotene intake up to end of 4-year follow-up period (approximately 57 months) for study PVO-1A-301. For study PVO-1A-001, adverse events (AEs) were collected from study day 1 up to approximately 37 months. While no pharmacological intervention was applied in this observational study (PVO-1A-001), safety issues resulting only from any study-related procedure were recorded as AEs. MedDRA version 21.0 for PVO-1A-001 study. The Safety analysis set included all enrolled participants who received at least 1 dose of palovarotene in study PVO-1A-301. The FAS included all participants in the Enrolled Analysis Set with FOP caused by the R206H mutation and who had baseline data in study PVO-1A-001.	3.7% 3/81 • Number of events 3 • Treatment-emergent adverse events are collected from first date of palovarotene intake up to end of 4-year follow-up period (approximately 57 months) for study PVO-1A-301. For study PVO-1A-001, adverse events (AEs) were collected from study day 1 up to approximately 37 months. While no pharmacological intervention was applied in this observational study (PVO-1A-001), safety issues resulting only from any study-related procedure were recorded as AEs. MedDRA version 21.0 for PVO-1A-001 study. The Safety analysis set included all enrolled participants who received at least 1 dose of palovarotene in study PVO-1A-301. The FAS included all participants in the Enrolled Analysis Set with FOP caused by the R206H mutation and who had baseline data in study PVO-1A-001.	0.00% 0/114 • Treatment-emergent adverse events are collected from first date of palovarotene intake up to end of 4-year follow-up period (approximately 57 months) for study PVO-1A-301. For study PVO-1A-001, adverse events (AEs) were collected from study day 1 up to approximately 37 months. While no pharmacological intervention was applied in this observational study (PVO-1A-001), safety issues resulting only from any study-related procedure were recorded as AEs. MedDRA version 21.0 for PVO-1A-001 study. The Safety analysis set included all enrolled participants who received at least 1 dose of palovarotene in study PVO-1A-301. The FAS included all participants in the Enrolled Analysis Set with FOP caused by the R206H mutation and who had baseline data in study PVO-1A-001.
Injury, poisoning and procedural complications Radius Fracture	0.93% 1/107 • Number of events 1 • Treatment-emergent adverse events are collected from first date of palovarotene intake up to end of 4-year follow-up period (approximately 57 months) for study PVO-1A-301. For study PVO-1A-001, adverse events (AEs) were collected from study day 1 up to approximately 37 months. While no pharmacological intervention was applied in this observational study (PVO-1A-001), safety issues resulting only from any study-related procedure were recorded as AEs. MedDRA version 21.0 for PVO-1A-001 study. The Safety analysis set included all enrolled participants who received at least 1 dose of palovarotene in study PVO-1A-301. The FAS included all participants in the Enrolled Analysis Set with FOP caused by the R206H mutation and who had baseline data in study PVO-1A-001.	0.00% 0/81 • Treatment-emergent adverse events are collected from first date of palovarotene intake up to end of 4-year follow-up period (approximately 57 months) for study PVO-1A-301. For study PVO-1A-001, adverse events (AEs) were collected from study day 1 up to approximately 37 months. While no pharmacological intervention was applied in this observational study (PVO-1A-001), safety issues resulting only from any study-related procedure were recorded as AEs. MedDRA version 21.0 for PVO-1A-001 study. The Safety analysis set included all enrolled participants who received at least 1 dose of palovarotene in study PVO-1A-301. The FAS included all participants in the Enrolled Analysis Set with FOP caused by the R206H mutation and who had baseline data in study PVO-1A-001.	0.00% 0/114 • Treatment-emergent adverse events are collected from first date of palovarotene intake up to end of 4-year follow-up period (approximately 57 months) for study PVO-1A-301. For study PVO-1A-001, adverse events (AEs) were collected from study day 1 up to approximately 37 months. While no pharmacological intervention was applied in this observational study (PVO-1A-001), safety issues resulting only from any study-related procedure were recorded as AEs. MedDRA version 21.0 for PVO-1A-001 study. The Safety analysis set included all enrolled participants who received at least 1 dose of palovarotene in study PVO-1A-301. The FAS included all participants in the Enrolled Analysis Set with FOP caused by the R206H mutation and who had baseline data in study PVO-1A-001.
Injury, poisoning and procedural complications Traumatic Fracture	0.00% 0/107 • Treatment-emergent adverse events are collected from first date of palovarotene intake up to end of 4-year follow-up period (approximately 57 months) for study PVO-1A-301. For study PVO-1A-001, adverse events (AEs) were collected from study day 1 up to approximately 37 months. While no pharmacological intervention was applied in this observational study (PVO-1A-001), safety issues resulting only from any study-related procedure were recorded as AEs. MedDRA version 21.0 for PVO-1A-001 study. The Safety analysis set included all enrolled participants who received at least 1 dose of palovarotene in study PVO-1A-301. The FAS included all participants in the Enrolled Analysis Set with FOP caused by the R206H mutation and who had baseline data in study PVO-1A-001.	1.2% 1/81 • Number of events 1 • Treatment-emergent adverse events are collected from first date of palovarotene intake up to end of 4-year follow-up period (approximately 57 months) for study PVO-1A-301. For study PVO-1A-001, adverse events (AEs) were collected from study day 1 up to approximately 37 months. While no pharmacological intervention was applied in this observational study (PVO-1A-001), safety issues resulting only from any study-related procedure were recorded as AEs. MedDRA version 21.0 for PVO-1A-001 study. The Safety analysis set included all enrolled participants who received at least 1 dose of palovarotene in study PVO-1A-301. The FAS included all participants in the Enrolled Analysis Set with FOP caused by the R206H mutation and who had baseline data in study PVO-1A-001.	0.00% 0/114 • Treatment-emergent adverse events are collected from first date of palovarotene intake up to end of 4-year follow-up period (approximately 57 months) for study PVO-1A-301. For study PVO-1A-001, adverse events (AEs) were collected from study day 1 up to approximately 37 months. While no pharmacological intervention was applied in this observational study (PVO-1A-001), safety issues resulting only from any study-related procedure were recorded as AEs. MedDRA version 21.0 for PVO-1A-001 study. The Safety analysis set included all enrolled participants who received at least 1 dose of palovarotene in study PVO-1A-301. The FAS included all participants in the Enrolled Analysis Set with FOP caused by the R206H mutation and who had baseline data in study PVO-1A-001.
Respiratory, thoracic and mediastinal disorders Dyspnea	0.93% 1/107 • Number of events 1 • Treatment-emergent adverse events are collected from first date of palovarotene intake up to end of 4-year follow-up period (approximately 57 months) for study PVO-1A-301. For study PVO-1A-001, adverse events (AEs) were collected from study day 1 up to approximately 37 months. While no pharmacological intervention was applied in this observational study (PVO-1A-001), safety issues resulting only from any study-related procedure were recorded as AEs. MedDRA version 21.0 for PVO-1A-001 study. The Safety analysis set included all enrolled participants who received at least 1 dose of palovarotene in study PVO-1A-301. The FAS included all participants in the Enrolled Analysis Set with FOP caused by the R206H mutation and who had baseline data in study PVO-1A-001.	0.00% 0/81 • Treatment-emergent adverse events are collected from first date of palovarotene intake up to end of 4-year follow-up period (approximately 57 months) for study PVO-1A-301. For study PVO-1A-001, adverse events (AEs) were collected from study day 1 up to approximately 37 months. While no pharmacological intervention was applied in this observational study (PVO-1A-001), safety issues resulting only from any study-related procedure were recorded as AEs. MedDRA version 21.0 for PVO-1A-001 study. The Safety analysis set included all enrolled participants who received at least 1 dose of palovarotene in study PVO-1A-301. The FAS included all participants in the Enrolled Analysis Set with FOP caused by the R206H mutation and who had baseline data in study PVO-1A-001.	0.00% 0/114 • Treatment-emergent adverse events are collected from first date of palovarotene intake up to end of 4-year follow-up period (approximately 57 months) for study PVO-1A-301. For study PVO-1A-001, adverse events (AEs) were collected from study day 1 up to approximately 37 months. While no pharmacological intervention was applied in this observational study (PVO-1A-001), safety issues resulting only from any study-related procedure were recorded as AEs. MedDRA version 21.0 for PVO-1A-001 study. The Safety analysis set included all enrolled participants who received at least 1 dose of palovarotene in study PVO-1A-301. The FAS included all participants in the Enrolled Analysis Set with FOP caused by the R206H mutation and who had baseline data in study PVO-1A-001.
Respiratory, thoracic and mediastinal disorders Respiratory Distress	0.93% 1/107 • Number of events 1 • Treatment-emergent adverse events are collected from first date of palovarotene intake up to end of 4-year follow-up period (approximately 57 months) for study PVO-1A-301. For study PVO-1A-001, adverse events (AEs) were collected from study day 1 up to approximately 37 months. While no pharmacological intervention was applied in this observational study (PVO-1A-001), safety issues resulting only from any study-related procedure were recorded as AEs. MedDRA version 21.0 for PVO-1A-001 study. The Safety analysis set included all enrolled participants who received at least 1 dose of palovarotene in study PVO-1A-301. The FAS included all participants in the Enrolled Analysis Set with FOP caused by the R206H mutation and who had baseline data in study PVO-1A-001.	0.00% 0/81 • Treatment-emergent adverse events are collected from first date of palovarotene intake up to end of 4-year follow-up period (approximately 57 months) for study PVO-1A-301. For study PVO-1A-001, adverse events (AEs) were collected from study day 1 up to approximately 37 months. While no pharmacological intervention was applied in this observational study (PVO-1A-001), safety issues resulting only from any study-related procedure were recorded as AEs. MedDRA version 21.0 for PVO-1A-001 study. The Safety analysis set included all enrolled participants who received at least 1 dose of palovarotene in study PVO-1A-301. The FAS included all participants in the Enrolled Analysis Set with FOP caused by the R206H mutation and who had baseline data in study PVO-1A-001.	0.00% 0/114 • Treatment-emergent adverse events are collected from first date of palovarotene intake up to end of 4-year follow-up period (approximately 57 months) for study PVO-1A-301. For study PVO-1A-001, adverse events (AEs) were collected from study day 1 up to approximately 37 months. While no pharmacological intervention was applied in this observational study (PVO-1A-001), safety issues resulting only from any study-related procedure were recorded as AEs. MedDRA version 21.0 for PVO-1A-001 study. The Safety analysis set included all enrolled participants who received at least 1 dose of palovarotene in study PVO-1A-301. The FAS included all participants in the Enrolled Analysis Set with FOP caused by the R206H mutation and who had baseline data in study PVO-1A-001.
Gastrointestinal disorders Abdominal Pain	0.93% 1/107 • Number of events 1 • Treatment-emergent adverse events are collected from first date of palovarotene intake up to end of 4-year follow-up period (approximately 57 months) for study PVO-1A-301. For study PVO-1A-001, adverse events (AEs) were collected from study day 1 up to approximately 37 months. While no pharmacological intervention was applied in this observational study (PVO-1A-001), safety issues resulting only from any study-related procedure were recorded as AEs. MedDRA version 21.0 for PVO-1A-001 study. The Safety analysis set included all enrolled participants who received at least 1 dose of palovarotene in study PVO-1A-301. The FAS included all participants in the Enrolled Analysis Set with FOP caused by the R206H mutation and who had baseline data in study PVO-1A-001.	0.00% 0/81 • Treatment-emergent adverse events are collected from first date of palovarotene intake up to end of 4-year follow-up period (approximately 57 months) for study PVO-1A-301. For study PVO-1A-001, adverse events (AEs) were collected from study day 1 up to approximately 37 months. While no pharmacological intervention was applied in this observational study (PVO-1A-001), safety issues resulting only from any study-related procedure were recorded as AEs. MedDRA version 21.0 for PVO-1A-001 study. The Safety analysis set included all enrolled participants who received at least 1 dose of palovarotene in study PVO-1A-301. The FAS included all participants in the Enrolled Analysis Set with FOP caused by the R206H mutation and who had baseline data in study PVO-1A-001.	0.00% 0/114 • Treatment-emergent adverse events are collected from first date of palovarotene intake up to end of 4-year follow-up period (approximately 57 months) for study PVO-1A-301. For study PVO-1A-001, adverse events (AEs) were collected from study day 1 up to approximately 37 months. While no pharmacological intervention was applied in this observational study (PVO-1A-001), safety issues resulting only from any study-related procedure were recorded as AEs. MedDRA version 21.0 for PVO-1A-001 study. The Safety analysis set included all enrolled participants who received at least 1 dose of palovarotene in study PVO-1A-301. The FAS included all participants in the Enrolled Analysis Set with FOP caused by the R206H mutation and who had baseline data in study PVO-1A-001.
Metabolism and nutrition disorders Malnutrition	0.00% 0/107 • Treatment-emergent adverse events are collected from first date of palovarotene intake up to end of 4-year follow-up period (approximately 57 months) for study PVO-1A-301. For study PVO-1A-001, adverse events (AEs) were collected from study day 1 up to approximately 37 months. While no pharmacological intervention was applied in this observational study (PVO-1A-001), safety issues resulting only from any study-related procedure were recorded as AEs. MedDRA version 21.0 for PVO-1A-001 study. The Safety analysis set included all enrolled participants who received at least 1 dose of palovarotene in study PVO-1A-301. The FAS included all participants in the Enrolled Analysis Set with FOP caused by the R206H mutation and who had baseline data in study PVO-1A-001.	1.2% 1/81 • Number of events 1 • Treatment-emergent adverse events are collected from first date of palovarotene intake up to end of 4-year follow-up period (approximately 57 months) for study PVO-1A-301. For study PVO-1A-001, adverse events (AEs) were collected from study day 1 up to approximately 37 months. While no pharmacological intervention was applied in this observational study (PVO-1A-001), safety issues resulting only from any study-related procedure were recorded as AEs. MedDRA version 21.0 for PVO-1A-001 study. The Safety analysis set included all enrolled participants who received at least 1 dose of palovarotene in study PVO-1A-301. The FAS included all participants in the Enrolled Analysis Set with FOP caused by the R206H mutation and who had baseline data in study PVO-1A-001.	0.00% 0/114 • Treatment-emergent adverse events are collected from first date of palovarotene intake up to end of 4-year follow-up period (approximately 57 months) for study PVO-1A-301. For study PVO-1A-001, adverse events (AEs) were collected from study day 1 up to approximately 37 months. While no pharmacological intervention was applied in this observational study (PVO-1A-001), safety issues resulting only from any study-related procedure were recorded as AEs. MedDRA version 21.0 for PVO-1A-001 study. The Safety analysis set included all enrolled participants who received at least 1 dose of palovarotene in study PVO-1A-301. The FAS included all participants in the Enrolled Analysis Set with FOP caused by the R206H mutation and who had baseline data in study PVO-1A-001.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Uterine Leiomyoma	0.93% 1/107 • Number of events 1 • Treatment-emergent adverse events are collected from first date of palovarotene intake up to end of 4-year follow-up period (approximately 57 months) for study PVO-1A-301. For study PVO-1A-001, adverse events (AEs) were collected from study day 1 up to approximately 37 months. While no pharmacological intervention was applied in this observational study (PVO-1A-001), safety issues resulting only from any study-related procedure were recorded as AEs. MedDRA version 21.0 for PVO-1A-001 study. The Safety analysis set included all enrolled participants who received at least 1 dose of palovarotene in study PVO-1A-301. The FAS included all participants in the Enrolled Analysis Set with FOP caused by the R206H mutation and who had baseline data in study PVO-1A-001.	0.00% 0/81 • Treatment-emergent adverse events are collected from first date of palovarotene intake up to end of 4-year follow-up period (approximately 57 months) for study PVO-1A-301. For study PVO-1A-001, adverse events (AEs) were collected from study day 1 up to approximately 37 months. While no pharmacological intervention was applied in this observational study (PVO-1A-001), safety issues resulting only from any study-related procedure were recorded as AEs. MedDRA version 21.0 for PVO-1A-001 study. The Safety analysis set included all enrolled participants who received at least 1 dose of palovarotene in study PVO-1A-301. The FAS included all participants in the Enrolled Analysis Set with FOP caused by the R206H mutation and who had baseline data in study PVO-1A-001.	0.00% 0/114 • Treatment-emergent adverse events are collected from first date of palovarotene intake up to end of 4-year follow-up period (approximately 57 months) for study PVO-1A-301. For study PVO-1A-001, adverse events (AEs) were collected from study day 1 up to approximately 37 months. While no pharmacological intervention was applied in this observational study (PVO-1A-001), safety issues resulting only from any study-related procedure were recorded as AEs. MedDRA version 21.0 for PVO-1A-001 study. The Safety analysis set included all enrolled participants who received at least 1 dose of palovarotene in study PVO-1A-301. The FAS included all participants in the Enrolled Analysis Set with FOP caused by the R206H mutation and who had baseline data in study PVO-1A-001.
Nervous system disorders Syncope	0.93% 1/107 • Number of events 1 • Treatment-emergent adverse events are collected from first date of palovarotene intake up to end of 4-year follow-up period (approximately 57 months) for study PVO-1A-301. For study PVO-1A-001, adverse events (AEs) were collected from study day 1 up to approximately 37 months. While no pharmacological intervention was applied in this observational study (PVO-1A-001), safety issues resulting only from any study-related procedure were recorded as AEs. MedDRA version 21.0 for PVO-1A-001 study. The Safety analysis set included all enrolled participants who received at least 1 dose of palovarotene in study PVO-1A-301. The FAS included all participants in the Enrolled Analysis Set with FOP caused by the R206H mutation and who had baseline data in study PVO-1A-001.	0.00% 0/81 • Treatment-emergent adverse events are collected from first date of palovarotene intake up to end of 4-year follow-up period (approximately 57 months) for study PVO-1A-301. For study PVO-1A-001, adverse events (AEs) were collected from study day 1 up to approximately 37 months. While no pharmacological intervention was applied in this observational study (PVO-1A-001), safety issues resulting only from any study-related procedure were recorded as AEs. MedDRA version 21.0 for PVO-1A-001 study. The Safety analysis set included all enrolled participants who received at least 1 dose of palovarotene in study PVO-1A-301. The FAS included all participants in the Enrolled Analysis Set with FOP caused by the R206H mutation and who had baseline data in study PVO-1A-001.	0.00% 0/114 • Treatment-emergent adverse events are collected from first date of palovarotene intake up to end of 4-year follow-up period (approximately 57 months) for study PVO-1A-301. For study PVO-1A-001, adverse events (AEs) were collected from study day 1 up to approximately 37 months. While no pharmacological intervention was applied in this observational study (PVO-1A-001), safety issues resulting only from any study-related procedure were recorded as AEs. MedDRA version 21.0 for PVO-1A-001 study. The Safety analysis set included all enrolled participants who received at least 1 dose of palovarotene in study PVO-1A-301. The FAS included all participants in the Enrolled Analysis Set with FOP caused by the R206H mutation and who had baseline data in study PVO-1A-001.
Blood and lymphatic system disorders Anemia	0.00% 0/107 • Treatment-emergent adverse events are collected from first date of palovarotene intake up to end of 4-year follow-up period (approximately 57 months) for study PVO-1A-301. For study PVO-1A-001, adverse events (AEs) were collected from study day 1 up to approximately 37 months. While no pharmacological intervention was applied in this observational study (PVO-1A-001), safety issues resulting only from any study-related procedure were recorded as AEs. MedDRA version 21.0 for PVO-1A-001 study. The Safety analysis set included all enrolled participants who received at least 1 dose of palovarotene in study PVO-1A-301. The FAS included all participants in the Enrolled Analysis Set with FOP caused by the R206H mutation and who had baseline data in study PVO-1A-001.	1.2% 1/81 • Number of events 1 • Treatment-emergent adverse events are collected from first date of palovarotene intake up to end of 4-year follow-up period (approximately 57 months) for study PVO-1A-301. For study PVO-1A-001, adverse events (AEs) were collected from study day 1 up to approximately 37 months. While no pharmacological intervention was applied in this observational study (PVO-1A-001), safety issues resulting only from any study-related procedure were recorded as AEs. MedDRA version 21.0 for PVO-1A-001 study. The Safety analysis set included all enrolled participants who received at least 1 dose of palovarotene in study PVO-1A-301. The FAS included all participants in the Enrolled Analysis Set with FOP caused by the R206H mutation and who had baseline data in study PVO-1A-001.	0.00% 0/114 • Treatment-emergent adverse events are collected from first date of palovarotene intake up to end of 4-year follow-up period (approximately 57 months) for study PVO-1A-301. For study PVO-1A-001, adverse events (AEs) were collected from study day 1 up to approximately 37 months. While no pharmacological intervention was applied in this observational study (PVO-1A-001), safety issues resulting only from any study-related procedure were recorded as AEs. MedDRA version 21.0 for PVO-1A-001 study. The Safety analysis set included all enrolled participants who received at least 1 dose of palovarotene in study PVO-1A-301. The FAS included all participants in the Enrolled Analysis Set with FOP caused by the R206H mutation and who had baseline data in study PVO-1A-001.
Musculoskeletal and connective tissue disorders Aneurysmal bone cyst	0.93% 1/107 • Number of events 1 • Treatment-emergent adverse events are collected from first date of palovarotene intake up to end of 4-year follow-up period (approximately 57 months) for study PVO-1A-301. For study PVO-1A-001, adverse events (AEs) were collected from study day 1 up to approximately 37 months. While no pharmacological intervention was applied in this observational study (PVO-1A-001), safety issues resulting only from any study-related procedure were recorded as AEs. MedDRA version 21.0 for PVO-1A-001 study. The Safety analysis set included all enrolled participants who received at least 1 dose of palovarotene in study PVO-1A-301. The FAS included all participants in the Enrolled Analysis Set with FOP caused by the R206H mutation and who had baseline data in study PVO-1A-001.	0.00% 0/81 • Treatment-emergent adverse events are collected from first date of palovarotene intake up to end of 4-year follow-up period (approximately 57 months) for study PVO-1A-301. For study PVO-1A-001, adverse events (AEs) were collected from study day 1 up to approximately 37 months. While no pharmacological intervention was applied in this observational study (PVO-1A-001), safety issues resulting only from any study-related procedure were recorded as AEs. MedDRA version 21.0 for PVO-1A-001 study. The Safety analysis set included all enrolled participants who received at least 1 dose of palovarotene in study PVO-1A-301. The FAS included all participants in the Enrolled Analysis Set with FOP caused by the R206H mutation and who had baseline data in study PVO-1A-001.	0.00% 0/114 • Treatment-emergent adverse events are collected from first date of palovarotene intake up to end of 4-year follow-up period (approximately 57 months) for study PVO-1A-301. For study PVO-1A-001, adverse events (AEs) were collected from study day 1 up to approximately 37 months. While no pharmacological intervention was applied in this observational study (PVO-1A-001), safety issues resulting only from any study-related procedure were recorded as AEs. MedDRA version 21.0 for PVO-1A-001 study. The Safety analysis set included all enrolled participants who received at least 1 dose of palovarotene in study PVO-1A-301. The FAS included all participants in the Enrolled Analysis Set with FOP caused by the R206H mutation and who had baseline data in study PVO-1A-001.
Musculoskeletal and connective tissue disorders Pain in extremity	0.93% 1/107 • Number of events 1 • Treatment-emergent adverse events are collected from first date of palovarotene intake up to end of 4-year follow-up period (approximately 57 months) for study PVO-1A-301. For study PVO-1A-001, adverse events (AEs) were collected from study day 1 up to approximately 37 months. While no pharmacological intervention was applied in this observational study (PVO-1A-001), safety issues resulting only from any study-related procedure were recorded as AEs. MedDRA version 21.0 for PVO-1A-001 study. The Safety analysis set included all enrolled participants who received at least 1 dose of palovarotene in study PVO-1A-301. The FAS included all participants in the Enrolled Analysis Set with FOP caused by the R206H mutation and who had baseline data in study PVO-1A-001.	0.00% 0/81 • Treatment-emergent adverse events are collected from first date of palovarotene intake up to end of 4-year follow-up period (approximately 57 months) for study PVO-1A-301. For study PVO-1A-001, adverse events (AEs) were collected from study day 1 up to approximately 37 months. While no pharmacological intervention was applied in this observational study (PVO-1A-001), safety issues resulting only from any study-related procedure were recorded as AEs. MedDRA version 21.0 for PVO-1A-001 study. The Safety analysis set included all enrolled participants who received at least 1 dose of palovarotene in study PVO-1A-301. The FAS included all participants in the Enrolled Analysis Set with FOP caused by the R206H mutation and who had baseline data in study PVO-1A-001.	0.00% 0/114 • Treatment-emergent adverse events are collected from first date of palovarotene intake up to end of 4-year follow-up period (approximately 57 months) for study PVO-1A-301. For study PVO-1A-001, adverse events (AEs) were collected from study day 1 up to approximately 37 months. While no pharmacological intervention was applied in this observational study (PVO-1A-001), safety issues resulting only from any study-related procedure were recorded as AEs. MedDRA version 21.0 for PVO-1A-001 study. The Safety analysis set included all enrolled participants who received at least 1 dose of palovarotene in study PVO-1A-301. The FAS included all participants in the Enrolled Analysis Set with FOP caused by the R206H mutation and who had baseline data in study PVO-1A-001.
Infections and infestations Corona virus infection	9.3% 10/107 • Number of events 10 • Treatment-emergent adverse events are collected from first date of palovarotene intake up to end of 4-year follow-up period (approximately 57 months) for study PVO-1A-301. For study PVO-1A-001, adverse events (AEs) were collected from study day 1 up to approximately 37 months. While no pharmacological intervention was applied in this observational study (PVO-1A-001), safety issues resulting only from any study-related procedure were recorded as AEs. MedDRA version 21.0 for PVO-1A-001 study. The Safety analysis set included all enrolled participants who received at least 1 dose of palovarotene in study PVO-1A-301. The FAS included all participants in the Enrolled Analysis Set with FOP caused by the R206H mutation and who had baseline data in study PVO-1A-001.	2.5% 2/81 • Number of events 2 • Treatment-emergent adverse events are collected from first date of palovarotene intake up to end of 4-year follow-up period (approximately 57 months) for study PVO-1A-301. For study PVO-1A-001, adverse events (AEs) were collected from study day 1 up to approximately 37 months. While no pharmacological intervention was applied in this observational study (PVO-1A-001), safety issues resulting only from any study-related procedure were recorded as AEs. MedDRA version 21.0 for PVO-1A-001 study. The Safety analysis set included all enrolled participants who received at least 1 dose of palovarotene in study PVO-1A-301. The FAS included all participants in the Enrolled Analysis Set with FOP caused by the R206H mutation and who had baseline data in study PVO-1A-001.	0.00% 0/114 • Treatment-emergent adverse events are collected from first date of palovarotene intake up to end of 4-year follow-up period (approximately 57 months) for study PVO-1A-301. For study PVO-1A-001, adverse events (AEs) were collected from study day 1 up to approximately 37 months. While no pharmacological intervention was applied in this observational study (PVO-1A-001), safety issues resulting only from any study-related procedure were recorded as AEs. MedDRA version 21.0 for PVO-1A-001 study. The Safety analysis set included all enrolled participants who received at least 1 dose of palovarotene in study PVO-1A-301. The FAS included all participants in the Enrolled Analysis Set with FOP caused by the R206H mutation and who had baseline data in study PVO-1A-001.
Vascular disorders Lymphoedema	0.93% 1/107 • Number of events 1 • Treatment-emergent adverse events are collected from first date of palovarotene intake up to end of 4-year follow-up period (approximately 57 months) for study PVO-1A-301. For study PVO-1A-001, adverse events (AEs) were collected from study day 1 up to approximately 37 months. While no pharmacological intervention was applied in this observational study (PVO-1A-001), safety issues resulting only from any study-related procedure were recorded as AEs. MedDRA version 21.0 for PVO-1A-001 study. The Safety analysis set included all enrolled participants who received at least 1 dose of palovarotene in study PVO-1A-301. The FAS included all participants in the Enrolled Analysis Set with FOP caused by the R206H mutation and who had baseline data in study PVO-1A-001.	0.00% 0/81 • Treatment-emergent adverse events are collected from first date of palovarotene intake up to end of 4-year follow-up period (approximately 57 months) for study PVO-1A-301. For study PVO-1A-001, adverse events (AEs) were collected from study day 1 up to approximately 37 months. While no pharmacological intervention was applied in this observational study (PVO-1A-001), safety issues resulting only from any study-related procedure were recorded as AEs. MedDRA version 21.0 for PVO-1A-001 study. The Safety analysis set included all enrolled participants who received at least 1 dose of palovarotene in study PVO-1A-301. The FAS included all participants in the Enrolled Analysis Set with FOP caused by the R206H mutation and who had baseline data in study PVO-1A-001.	0.00% 0/114 • Treatment-emergent adverse events are collected from first date of palovarotene intake up to end of 4-year follow-up period (approximately 57 months) for study PVO-1A-301. For study PVO-1A-001, adverse events (AEs) were collected from study day 1 up to approximately 37 months. While no pharmacological intervention was applied in this observational study (PVO-1A-001), safety issues resulting only from any study-related procedure were recorded as AEs. MedDRA version 21.0 for PVO-1A-001 study. The Safety analysis set included all enrolled participants who received at least 1 dose of palovarotene in study PVO-1A-301. The FAS included all participants in the Enrolled Analysis Set with FOP caused by the R206H mutation and who had baseline data in study PVO-1A-001.
Injury, poisoning and procedural complications Post procedural haematoma	0.93% 1/107 • Number of events 2 • Treatment-emergent adverse events are collected from first date of palovarotene intake up to end of 4-year follow-up period (approximately 57 months) for study PVO-1A-301. For study PVO-1A-001, adverse events (AEs) were collected from study day 1 up to approximately 37 months. While no pharmacological intervention was applied in this observational study (PVO-1A-001), safety issues resulting only from any study-related procedure were recorded as AEs. MedDRA version 21.0 for PVO-1A-001 study. The Safety analysis set included all enrolled participants who received at least 1 dose of palovarotene in study PVO-1A-301. The FAS included all participants in the Enrolled Analysis Set with FOP caused by the R206H mutation and who had baseline data in study PVO-1A-001.	0.00% 0/81 • Treatment-emergent adverse events are collected from first date of palovarotene intake up to end of 4-year follow-up period (approximately 57 months) for study PVO-1A-301. For study PVO-1A-001, adverse events (AEs) were collected from study day 1 up to approximately 37 months. While no pharmacological intervention was applied in this observational study (PVO-1A-001), safety issues resulting only from any study-related procedure were recorded as AEs. MedDRA version 21.0 for PVO-1A-001 study. The Safety analysis set included all enrolled participants who received at least 1 dose of palovarotene in study PVO-1A-301. The FAS included all participants in the Enrolled Analysis Set with FOP caused by the R206H mutation and who had baseline data in study PVO-1A-001.	0.00% 0/114 • Treatment-emergent adverse events are collected from first date of palovarotene intake up to end of 4-year follow-up period (approximately 57 months) for study PVO-1A-301. For study PVO-1A-001, adverse events (AEs) were collected from study day 1 up to approximately 37 months. While no pharmacological intervention was applied in this observational study (PVO-1A-001), safety issues resulting only from any study-related procedure were recorded as AEs. MedDRA version 21.0 for PVO-1A-001 study. The Safety analysis set included all enrolled participants who received at least 1 dose of palovarotene in study PVO-1A-301. The FAS included all participants in the Enrolled Analysis Set with FOP caused by the R206H mutation and who had baseline data in study PVO-1A-001.
Injury, poisoning and procedural complications Exposure to communicable disease	2.8% 3/107 • Number of events 3 • Treatment-emergent adverse events are collected from first date of palovarotene intake up to end of 4-year follow-up period (approximately 57 months) for study PVO-1A-301. For study PVO-1A-001, adverse events (AEs) were collected from study day 1 up to approximately 37 months. While no pharmacological intervention was applied in this observational study (PVO-1A-001), safety issues resulting only from any study-related procedure were recorded as AEs. MedDRA version 21.0 for PVO-1A-001 study. The Safety analysis set included all enrolled participants who received at least 1 dose of palovarotene in study PVO-1A-301. The FAS included all participants in the Enrolled Analysis Set with FOP caused by the R206H mutation and who had baseline data in study PVO-1A-001.	0.00% 0/81 • Treatment-emergent adverse events are collected from first date of palovarotene intake up to end of 4-year follow-up period (approximately 57 months) for study PVO-1A-301. For study PVO-1A-001, adverse events (AEs) were collected from study day 1 up to approximately 37 months. While no pharmacological intervention was applied in this observational study (PVO-1A-001), safety issues resulting only from any study-related procedure were recorded as AEs. MedDRA version 21.0 for PVO-1A-001 study. The Safety analysis set included all enrolled participants who received at least 1 dose of palovarotene in study PVO-1A-301. The FAS included all participants in the Enrolled Analysis Set with FOP caused by the R206H mutation and who had baseline data in study PVO-1A-001.	0.00% 0/114 • Treatment-emergent adverse events are collected from first date of palovarotene intake up to end of 4-year follow-up period (approximately 57 months) for study PVO-1A-301. For study PVO-1A-001, adverse events (AEs) were collected from study day 1 up to approximately 37 months. While no pharmacological intervention was applied in this observational study (PVO-1A-001), safety issues resulting only from any study-related procedure were recorded as AEs. MedDRA version 21.0 for PVO-1A-001 study. The Safety analysis set included all enrolled participants who received at least 1 dose of palovarotene in study PVO-1A-301. The FAS included all participants in the Enrolled Analysis Set with FOP caused by the R206H mutation and who had baseline data in study PVO-1A-001.

Other adverse events

Measure	Palovarotene 5 mg n=107 participants at risk Participants were administered 5 mg palovarotene orally once daily up to 48 months.	Palovarotene 20/10 mg n=81 participants at risk Participants with flare-up symptoms or traumatic events received palovarotene 20 mg once daily for 4 weeks after the flare-up confirmation by the Investigator. Followed by palovarotene 10 mg once daily for 8 weeks.	Untreated (PVO-1A-001) n=114 participants at risk Participants from study PVO-1A-001 (NCT02322255) were included with FOP caused by the R206H mutation and with baseline data. Participants were not administered palovarotene in this study and only compared as external control. While no pharmacological intervention was applied in this observational study, safety issues resulting only from any study-related procedure were recorded as AEs.
Skin and subcutaneous tissue disorders Dry skin	56.1% 60/107 • Number of events 95 • Treatment-emergent adverse events are collected from first date of palovarotene intake up to end of 4-year follow-up period (approximately 57 months) for study PVO-1A-301. For study PVO-1A-001, adverse events (AEs) were collected from study day 1 up to approximately 37 months. While no pharmacological intervention was applied in this observational study (PVO-1A-001), safety issues resulting only from any study-related procedure were recorded as AEs. MedDRA version 21.0 for PVO-1A-001 study. The Safety analysis set included all enrolled participants who received at least 1 dose of palovarotene in study PVO-1A-301. The FAS included all participants in the Enrolled Analysis Set with FOP caused by the R206H mutation and who had baseline data in study PVO-1A-001.	45.7% 37/81 • Number of events 77 • Treatment-emergent adverse events are collected from first date of palovarotene intake up to end of 4-year follow-up period (approximately 57 months) for study PVO-1A-301. For study PVO-1A-001, adverse events (AEs) were collected from study day 1 up to approximately 37 months. While no pharmacological intervention was applied in this observational study (PVO-1A-001), safety issues resulting only from any study-related procedure were recorded as AEs. MedDRA version 21.0 for PVO-1A-001 study. The Safety analysis set included all enrolled participants who received at least 1 dose of palovarotene in study PVO-1A-301. The FAS included all participants in the Enrolled Analysis Set with FOP caused by the R206H mutation and who had baseline data in study PVO-1A-001.	0.00% 0/114 • Treatment-emergent adverse events are collected from first date of palovarotene intake up to end of 4-year follow-up period (approximately 57 months) for study PVO-1A-301. For study PVO-1A-001, adverse events (AEs) were collected from study day 1 up to approximately 37 months. While no pharmacological intervention was applied in this observational study (PVO-1A-001), safety issues resulting only from any study-related procedure were recorded as AEs. MedDRA version 21.0 for PVO-1A-001 study. The Safety analysis set included all enrolled participants who received at least 1 dose of palovarotene in study PVO-1A-301. The FAS included all participants in the Enrolled Analysis Set with FOP caused by the R206H mutation and who had baseline data in study PVO-1A-001.
Skin and subcutaneous tissue disorders Alopecia	17.8% 19/107 • Number of events 23 • Treatment-emergent adverse events are collected from first date of palovarotene intake up to end of 4-year follow-up period (approximately 57 months) for study PVO-1A-301. For study PVO-1A-001, adverse events (AEs) were collected from study day 1 up to approximately 37 months. While no pharmacological intervention was applied in this observational study (PVO-1A-001), safety issues resulting only from any study-related procedure were recorded as AEs. MedDRA version 21.0 for PVO-1A-001 study. The Safety analysis set included all enrolled participants who received at least 1 dose of palovarotene in study PVO-1A-301. The FAS included all participants in the Enrolled Analysis Set with FOP caused by the R206H mutation and who had baseline data in study PVO-1A-001.	25.9% 21/81 • Number of events 28 • Treatment-emergent adverse events are collected from first date of palovarotene intake up to end of 4-year follow-up period (approximately 57 months) for study PVO-1A-301. For study PVO-1A-001, adverse events (AEs) were collected from study day 1 up to approximately 37 months. While no pharmacological intervention was applied in this observational study (PVO-1A-001), safety issues resulting only from any study-related procedure were recorded as AEs. MedDRA version 21.0 for PVO-1A-001 study. The Safety analysis set included all enrolled participants who received at least 1 dose of palovarotene in study PVO-1A-301. The FAS included all participants in the Enrolled Analysis Set with FOP caused by the R206H mutation and who had baseline data in study PVO-1A-001.	0.00% 0/114 • Treatment-emergent adverse events are collected from first date of palovarotene intake up to end of 4-year follow-up period (approximately 57 months) for study PVO-1A-301. For study PVO-1A-001, adverse events (AEs) were collected from study day 1 up to approximately 37 months. While no pharmacological intervention was applied in this observational study (PVO-1A-001), safety issues resulting only from any study-related procedure were recorded as AEs. MedDRA version 21.0 for PVO-1A-001 study. The Safety analysis set included all enrolled participants who received at least 1 dose of palovarotene in study PVO-1A-301. The FAS included all participants in the Enrolled Analysis Set with FOP caused by the R206H mutation and who had baseline data in study PVO-1A-001.
Skin and subcutaneous tissue disorders Drug eruption	14.0% 15/107 • Number of events 24 • Treatment-emergent adverse events are collected from first date of palovarotene intake up to end of 4-year follow-up period (approximately 57 months) for study PVO-1A-301. For study PVO-1A-001, adverse events (AEs) were collected from study day 1 up to approximately 37 months. While no pharmacological intervention was applied in this observational study (PVO-1A-001), safety issues resulting only from any study-related procedure were recorded as AEs. MedDRA version 21.0 for PVO-1A-001 study. The Safety analysis set included all enrolled participants who received at least 1 dose of palovarotene in study PVO-1A-301. The FAS included all participants in the Enrolled Analysis Set with FOP caused by the R206H mutation and who had baseline data in study PVO-1A-001.	32.1% 26/81 • Number of events 40 • Treatment-emergent adverse events are collected from first date of palovarotene intake up to end of 4-year follow-up period (approximately 57 months) for study PVO-1A-301. For study PVO-1A-001, adverse events (AEs) were collected from study day 1 up to approximately 37 months. While no pharmacological intervention was applied in this observational study (PVO-1A-001), safety issues resulting only from any study-related procedure were recorded as AEs. MedDRA version 21.0 for PVO-1A-001 study. The Safety analysis set included all enrolled participants who received at least 1 dose of palovarotene in study PVO-1A-301. The FAS included all participants in the Enrolled Analysis Set with FOP caused by the R206H mutation and who had baseline data in study PVO-1A-001.	0.00% 0/114 • Treatment-emergent adverse events are collected from first date of palovarotene intake up to end of 4-year follow-up period (approximately 57 months) for study PVO-1A-301. For study PVO-1A-001, adverse events (AEs) were collected from study day 1 up to approximately 37 months. While no pharmacological intervention was applied in this observational study (PVO-1A-001), safety issues resulting only from any study-related procedure were recorded as AEs. MedDRA version 21.0 for PVO-1A-001 study. The Safety analysis set included all enrolled participants who received at least 1 dose of palovarotene in study PVO-1A-301. The FAS included all participants in the Enrolled Analysis Set with FOP caused by the R206H mutation and who had baseline data in study PVO-1A-001.
Skin and subcutaneous tissue disorders Pruritus	17.8% 19/107 • Number of events 29 • Treatment-emergent adverse events are collected from first date of palovarotene intake up to end of 4-year follow-up period (approximately 57 months) for study PVO-1A-301. For study PVO-1A-001, adverse events (AEs) were collected from study day 1 up to approximately 37 months. While no pharmacological intervention was applied in this observational study (PVO-1A-001), safety issues resulting only from any study-related procedure were recorded as AEs. MedDRA version 21.0 for PVO-1A-001 study. The Safety analysis set included all enrolled participants who received at least 1 dose of palovarotene in study PVO-1A-301. The FAS included all participants in the Enrolled Analysis Set with FOP caused by the R206H mutation and who had baseline data in study PVO-1A-001.	17.3% 14/81 • Number of events 16 • Treatment-emergent adverse events are collected from first date of palovarotene intake up to end of 4-year follow-up period (approximately 57 months) for study PVO-1A-301. For study PVO-1A-001, adverse events (AEs) were collected from study day 1 up to approximately 37 months. While no pharmacological intervention was applied in this observational study (PVO-1A-001), safety issues resulting only from any study-related procedure were recorded as AEs. MedDRA version 21.0 for PVO-1A-001 study. The Safety analysis set included all enrolled participants who received at least 1 dose of palovarotene in study PVO-1A-301. The FAS included all participants in the Enrolled Analysis Set with FOP caused by the R206H mutation and who had baseline data in study PVO-1A-001.	0.00% 0/114 • Treatment-emergent adverse events are collected from first date of palovarotene intake up to end of 4-year follow-up period (approximately 57 months) for study PVO-1A-301. For study PVO-1A-001, adverse events (AEs) were collected from study day 1 up to approximately 37 months. While no pharmacological intervention was applied in this observational study (PVO-1A-001), safety issues resulting only from any study-related procedure were recorded as AEs. MedDRA version 21.0 for PVO-1A-001 study. The Safety analysis set included all enrolled participants who received at least 1 dose of palovarotene in study PVO-1A-301. The FAS included all participants in the Enrolled Analysis Set with FOP caused by the R206H mutation and who had baseline data in study PVO-1A-001.
Skin and subcutaneous tissue disorders Rash	23.4% 25/107 • Number of events 40 • Treatment-emergent adverse events are collected from first date of palovarotene intake up to end of 4-year follow-up period (approximately 57 months) for study PVO-1A-301. For study PVO-1A-001, adverse events (AEs) were collected from study day 1 up to approximately 37 months. While no pharmacological intervention was applied in this observational study (PVO-1A-001), safety issues resulting only from any study-related procedure were recorded as AEs. MedDRA version 21.0 for PVO-1A-001 study. The Safety analysis set included all enrolled participants who received at least 1 dose of palovarotene in study PVO-1A-301. The FAS included all participants in the Enrolled Analysis Set with FOP caused by the R206H mutation and who had baseline data in study PVO-1A-001.	13.6% 11/81 • Number of events 22 • Treatment-emergent adverse events are collected from first date of palovarotene intake up to end of 4-year follow-up period (approximately 57 months) for study PVO-1A-301. For study PVO-1A-001, adverse events (AEs) were collected from study day 1 up to approximately 37 months. While no pharmacological intervention was applied in this observational study (PVO-1A-001), safety issues resulting only from any study-related procedure were recorded as AEs. MedDRA version 21.0 for PVO-1A-001 study. The Safety analysis set included all enrolled participants who received at least 1 dose of palovarotene in study PVO-1A-301. The FAS included all participants in the Enrolled Analysis Set with FOP caused by the R206H mutation and who had baseline data in study PVO-1A-001.	0.00% 0/114 • Treatment-emergent adverse events are collected from first date of palovarotene intake up to end of 4-year follow-up period (approximately 57 months) for study PVO-1A-301. For study PVO-1A-001, adverse events (AEs) were collected from study day 1 up to approximately 37 months. While no pharmacological intervention was applied in this observational study (PVO-1A-001), safety issues resulting only from any study-related procedure were recorded as AEs. MedDRA version 21.0 for PVO-1A-001 study. The Safety analysis set included all enrolled participants who received at least 1 dose of palovarotene in study PVO-1A-301. The FAS included all participants in the Enrolled Analysis Set with FOP caused by the R206H mutation and who had baseline data in study PVO-1A-001.
Skin and subcutaneous tissue disorders Erythema	10.3% 11/107 • Number of events 15 • Treatment-emergent adverse events are collected from first date of palovarotene intake up to end of 4-year follow-up period (approximately 57 months) for study PVO-1A-301. For study PVO-1A-001, adverse events (AEs) were collected from study day 1 up to approximately 37 months. While no pharmacological intervention was applied in this observational study (PVO-1A-001), safety issues resulting only from any study-related procedure were recorded as AEs. MedDRA version 21.0 for PVO-1A-001 study. The Safety analysis set included all enrolled participants who received at least 1 dose of palovarotene in study PVO-1A-301. The FAS included all participants in the Enrolled Analysis Set with FOP caused by the R206H mutation and who had baseline data in study PVO-1A-001.	19.8% 16/81 • Number of events 21 • Treatment-emergent adverse events are collected from first date of palovarotene intake up to end of 4-year follow-up period (approximately 57 months) for study PVO-1A-301. For study PVO-1A-001, adverse events (AEs) were collected from study day 1 up to approximately 37 months. While no pharmacological intervention was applied in this observational study (PVO-1A-001), safety issues resulting only from any study-related procedure were recorded as AEs. MedDRA version 21.0 for PVO-1A-001 study. The Safety analysis set included all enrolled participants who received at least 1 dose of palovarotene in study PVO-1A-301. The FAS included all participants in the Enrolled Analysis Set with FOP caused by the R206H mutation and who had baseline data in study PVO-1A-001.	0.00% 0/114 • Treatment-emergent adverse events are collected from first date of palovarotene intake up to end of 4-year follow-up period (approximately 57 months) for study PVO-1A-301. For study PVO-1A-001, adverse events (AEs) were collected from study day 1 up to approximately 37 months. While no pharmacological intervention was applied in this observational study (PVO-1A-001), safety issues resulting only from any study-related procedure were recorded as AEs. MedDRA version 21.0 for PVO-1A-001 study. The Safety analysis set included all enrolled participants who received at least 1 dose of palovarotene in study PVO-1A-301. The FAS included all participants in the Enrolled Analysis Set with FOP caused by the R206H mutation and who had baseline data in study PVO-1A-001.
Skin and subcutaneous tissue disorders Skin exfoliation	10.3% 11/107 • Number of events 14 • Treatment-emergent adverse events are collected from first date of palovarotene intake up to end of 4-year follow-up period (approximately 57 months) for study PVO-1A-301. For study PVO-1A-001, adverse events (AEs) were collected from study day 1 up to approximately 37 months. While no pharmacological intervention was applied in this observational study (PVO-1A-001), safety issues resulting only from any study-related procedure were recorded as AEs. MedDRA version 21.0 for PVO-1A-001 study. The Safety analysis set included all enrolled participants who received at least 1 dose of palovarotene in study PVO-1A-301. The FAS included all participants in the Enrolled Analysis Set with FOP caused by the R206H mutation and who had baseline data in study PVO-1A-001.	13.6% 11/81 • Number of events 23 • Treatment-emergent adverse events are collected from first date of palovarotene intake up to end of 4-year follow-up period (approximately 57 months) for study PVO-1A-301. For study PVO-1A-001, adverse events (AEs) were collected from study day 1 up to approximately 37 months. While no pharmacological intervention was applied in this observational study (PVO-1A-001), safety issues resulting only from any study-related procedure were recorded as AEs. MedDRA version 21.0 for PVO-1A-001 study. The Safety analysis set included all enrolled participants who received at least 1 dose of palovarotene in study PVO-1A-301. The FAS included all participants in the Enrolled Analysis Set with FOP caused by the R206H mutation and who had baseline data in study PVO-1A-001.	0.00% 0/114 • Treatment-emergent adverse events are collected from first date of palovarotene intake up to end of 4-year follow-up period (approximately 57 months) for study PVO-1A-301. For study PVO-1A-001, adverse events (AEs) were collected from study day 1 up to approximately 37 months. While no pharmacological intervention was applied in this observational study (PVO-1A-001), safety issues resulting only from any study-related procedure were recorded as AEs. MedDRA version 21.0 for PVO-1A-001 study. The Safety analysis set included all enrolled participants who received at least 1 dose of palovarotene in study PVO-1A-301. The FAS included all participants in the Enrolled Analysis Set with FOP caused by the R206H mutation and who had baseline data in study PVO-1A-001.
Skin and subcutaneous tissue disorders Skin irritation	5.6% 6/107 • Number of events 9 • Treatment-emergent adverse events are collected from first date of palovarotene intake up to end of 4-year follow-up period (approximately 57 months) for study PVO-1A-301. For study PVO-1A-001, adverse events (AEs) were collected from study day 1 up to approximately 37 months. While no pharmacological intervention was applied in this observational study (PVO-1A-001), safety issues resulting only from any study-related procedure were recorded as AEs. MedDRA version 21.0 for PVO-1A-001 study. The Safety analysis set included all enrolled participants who received at least 1 dose of palovarotene in study PVO-1A-301. The FAS included all participants in the Enrolled Analysis Set with FOP caused by the R206H mutation and who had baseline data in study PVO-1A-001.	6.2% 5/81 • Number of events 6 • Treatment-emergent adverse events are collected from first date of palovarotene intake up to end of 4-year follow-up period (approximately 57 months) for study PVO-1A-301. For study PVO-1A-001, adverse events (AEs) were collected from study day 1 up to approximately 37 months. While no pharmacological intervention was applied in this observational study (PVO-1A-001), safety issues resulting only from any study-related procedure were recorded as AEs. MedDRA version 21.0 for PVO-1A-001 study. The Safety analysis set included all enrolled participants who received at least 1 dose of palovarotene in study PVO-1A-301. The FAS included all participants in the Enrolled Analysis Set with FOP caused by the R206H mutation and who had baseline data in study PVO-1A-001.	0.00% 0/114 • Treatment-emergent adverse events are collected from first date of palovarotene intake up to end of 4-year follow-up period (approximately 57 months) for study PVO-1A-301. For study PVO-1A-001, adverse events (AEs) were collected from study day 1 up to approximately 37 months. While no pharmacological intervention was applied in this observational study (PVO-1A-001), safety issues resulting only from any study-related procedure were recorded as AEs. MedDRA version 21.0 for PVO-1A-001 study. The Safety analysis set included all enrolled participants who received at least 1 dose of palovarotene in study PVO-1A-301. The FAS included all participants in the Enrolled Analysis Set with FOP caused by the R206H mutation and who had baseline data in study PVO-1A-001.
Skin and subcutaneous tissue disorders Rash generalized	5.6% 6/107 • Number of events 9 • Treatment-emergent adverse events are collected from first date of palovarotene intake up to end of 4-year follow-up period (approximately 57 months) for study PVO-1A-301. For study PVO-1A-001, adverse events (AEs) were collected from study day 1 up to approximately 37 months. While no pharmacological intervention was applied in this observational study (PVO-1A-001), safety issues resulting only from any study-related procedure were recorded as AEs. MedDRA version 21.0 for PVO-1A-001 study. The Safety analysis set included all enrolled participants who received at least 1 dose of palovarotene in study PVO-1A-301. The FAS included all participants in the Enrolled Analysis Set with FOP caused by the R206H mutation and who had baseline data in study PVO-1A-001.	4.9% 4/81 • Number of events 5 • Treatment-emergent adverse events are collected from first date of palovarotene intake up to end of 4-year follow-up period (approximately 57 months) for study PVO-1A-301. For study PVO-1A-001, adverse events (AEs) were collected from study day 1 up to approximately 37 months. While no pharmacological intervention was applied in this observational study (PVO-1A-001), safety issues resulting only from any study-related procedure were recorded as AEs. MedDRA version 21.0 for PVO-1A-001 study. The Safety analysis set included all enrolled participants who received at least 1 dose of palovarotene in study PVO-1A-301. The FAS included all participants in the Enrolled Analysis Set with FOP caused by the R206H mutation and who had baseline data in study PVO-1A-001.	0.00% 0/114 • Treatment-emergent adverse events are collected from first date of palovarotene intake up to end of 4-year follow-up period (approximately 57 months) for study PVO-1A-301. For study PVO-1A-001, adverse events (AEs) were collected from study day 1 up to approximately 37 months. While no pharmacological intervention was applied in this observational study (PVO-1A-001), safety issues resulting only from any study-related procedure were recorded as AEs. MedDRA version 21.0 for PVO-1A-001 study. The Safety analysis set included all enrolled participants who received at least 1 dose of palovarotene in study PVO-1A-301. The FAS included all participants in the Enrolled Analysis Set with FOP caused by the R206H mutation and who had baseline data in study PVO-1A-001.
Skin and subcutaneous tissue disorders Dermatitis	2.8% 3/107 • Number of events 3 • Treatment-emergent adverse events are collected from first date of palovarotene intake up to end of 4-year follow-up period (approximately 57 months) for study PVO-1A-301. For study PVO-1A-001, adverse events (AEs) were collected from study day 1 up to approximately 37 months. While no pharmacological intervention was applied in this observational study (PVO-1A-001), safety issues resulting only from any study-related procedure were recorded as AEs. MedDRA version 21.0 for PVO-1A-001 study. The Safety analysis set included all enrolled participants who received at least 1 dose of palovarotene in study PVO-1A-301. The FAS included all participants in the Enrolled Analysis Set with FOP caused by the R206H mutation and who had baseline data in study PVO-1A-001.	8.6% 7/81 • Number of events 8 • Treatment-emergent adverse events are collected from first date of palovarotene intake up to end of 4-year follow-up period (approximately 57 months) for study PVO-1A-301. For study PVO-1A-001, adverse events (AEs) were collected from study day 1 up to approximately 37 months. While no pharmacological intervention was applied in this observational study (PVO-1A-001), safety issues resulting only from any study-related procedure were recorded as AEs. MedDRA version 21.0 for PVO-1A-001 study. The Safety analysis set included all enrolled participants who received at least 1 dose of palovarotene in study PVO-1A-301. The FAS included all participants in the Enrolled Analysis Set with FOP caused by the R206H mutation and who had baseline data in study PVO-1A-001.	0.00% 0/114 • Treatment-emergent adverse events are collected from first date of palovarotene intake up to end of 4-year follow-up period (approximately 57 months) for study PVO-1A-301. For study PVO-1A-001, adverse events (AEs) were collected from study day 1 up to approximately 37 months. While no pharmacological intervention was applied in this observational study (PVO-1A-001), safety issues resulting only from any study-related procedure were recorded as AEs. MedDRA version 21.0 for PVO-1A-001 study. The Safety analysis set included all enrolled participants who received at least 1 dose of palovarotene in study PVO-1A-301. The FAS included all participants in the Enrolled Analysis Set with FOP caused by the R206H mutation and who had baseline data in study PVO-1A-001.
Gastrointestinal disorders Lip Dry	34.6% 37/107 • Number of events 38 • Treatment-emergent adverse events are collected from first date of palovarotene intake up to end of 4-year follow-up period (approximately 57 months) for study PVO-1A-301. For study PVO-1A-001, adverse events (AEs) were collected from study day 1 up to approximately 37 months. While no pharmacological intervention was applied in this observational study (PVO-1A-001), safety issues resulting only from any study-related procedure were recorded as AEs. MedDRA version 21.0 for PVO-1A-001 study. The Safety analysis set included all enrolled participants who received at least 1 dose of palovarotene in study PVO-1A-301. The FAS included all participants in the Enrolled Analysis Set with FOP caused by the R206H mutation and who had baseline data in study PVO-1A-001.	21.0% 17/81 • Number of events 17 • Treatment-emergent adverse events are collected from first date of palovarotene intake up to end of 4-year follow-up period (approximately 57 months) for study PVO-1A-301. For study PVO-1A-001, adverse events (AEs) were collected from study day 1 up to approximately 37 months. While no pharmacological intervention was applied in this observational study (PVO-1A-001), safety issues resulting only from any study-related procedure were recorded as AEs. MedDRA version 21.0 for PVO-1A-001 study. The Safety analysis set included all enrolled participants who received at least 1 dose of palovarotene in study PVO-1A-301. The FAS included all participants in the Enrolled Analysis Set with FOP caused by the R206H mutation and who had baseline data in study PVO-1A-001.	0.00% 0/114 • Treatment-emergent adverse events are collected from first date of palovarotene intake up to end of 4-year follow-up period (approximately 57 months) for study PVO-1A-301. For study PVO-1A-001, adverse events (AEs) were collected from study day 1 up to approximately 37 months. While no pharmacological intervention was applied in this observational study (PVO-1A-001), safety issues resulting only from any study-related procedure were recorded as AEs. MedDRA version 21.0 for PVO-1A-001 study. The Safety analysis set included all enrolled participants who received at least 1 dose of palovarotene in study PVO-1A-301. The FAS included all participants in the Enrolled Analysis Set with FOP caused by the R206H mutation and who had baseline data in study PVO-1A-001.
Gastrointestinal disorders Chapped Lips	5.6% 6/107 • Number of events 7 • Treatment-emergent adverse events are collected from first date of palovarotene intake up to end of 4-year follow-up period (approximately 57 months) for study PVO-1A-301. For study PVO-1A-001, adverse events (AEs) were collected from study day 1 up to approximately 37 months. While no pharmacological intervention was applied in this observational study (PVO-1A-001), safety issues resulting only from any study-related procedure were recorded as AEs. MedDRA version 21.0 for PVO-1A-001 study. The Safety analysis set included all enrolled participants who received at least 1 dose of palovarotene in study PVO-1A-301. The FAS included all participants in the Enrolled Analysis Set with FOP caused by the R206H mutation and who had baseline data in study PVO-1A-001.	12.3% 10/81 • Number of events 11 • Treatment-emergent adverse events are collected from first date of palovarotene intake up to end of 4-year follow-up period (approximately 57 months) for study PVO-1A-301. For study PVO-1A-001, adverse events (AEs) were collected from study day 1 up to approximately 37 months. While no pharmacological intervention was applied in this observational study (PVO-1A-001), safety issues resulting only from any study-related procedure were recorded as AEs. MedDRA version 21.0 for PVO-1A-001 study. The Safety analysis set included all enrolled participants who received at least 1 dose of palovarotene in study PVO-1A-301. The FAS included all participants in the Enrolled Analysis Set with FOP caused by the R206H mutation and who had baseline data in study PVO-1A-001.	0.00% 0/114 • Treatment-emergent adverse events are collected from first date of palovarotene intake up to end of 4-year follow-up period (approximately 57 months) for study PVO-1A-301. For study PVO-1A-001, adverse events (AEs) were collected from study day 1 up to approximately 37 months. While no pharmacological intervention was applied in this observational study (PVO-1A-001), safety issues resulting only from any study-related procedure were recorded as AEs. MedDRA version 21.0 for PVO-1A-001 study. The Safety analysis set included all enrolled participants who received at least 1 dose of palovarotene in study PVO-1A-301. The FAS included all participants in the Enrolled Analysis Set with FOP caused by the R206H mutation and who had baseline data in study PVO-1A-001.
Gastrointestinal disorders Vomiting	10.3% 11/107 • Number of events 14 • Treatment-emergent adverse events are collected from first date of palovarotene intake up to end of 4-year follow-up period (approximately 57 months) for study PVO-1A-301. For study PVO-1A-001, adverse events (AEs) were collected from study day 1 up to approximately 37 months. While no pharmacological intervention was applied in this observational study (PVO-1A-001), safety issues resulting only from any study-related procedure were recorded as AEs. MedDRA version 21.0 for PVO-1A-001 study. The Safety analysis set included all enrolled participants who received at least 1 dose of palovarotene in study PVO-1A-301. The FAS included all participants in the Enrolled Analysis Set with FOP caused by the R206H mutation and who had baseline data in study PVO-1A-001.	6.2% 5/81 • Number of events 5 • Treatment-emergent adverse events are collected from first date of palovarotene intake up to end of 4-year follow-up period (approximately 57 months) for study PVO-1A-301. For study PVO-1A-001, adverse events (AEs) were collected from study day 1 up to approximately 37 months. While no pharmacological intervention was applied in this observational study (PVO-1A-001), safety issues resulting only from any study-related procedure were recorded as AEs. MedDRA version 21.0 for PVO-1A-001 study. The Safety analysis set included all enrolled participants who received at least 1 dose of palovarotene in study PVO-1A-301. The FAS included all participants in the Enrolled Analysis Set with FOP caused by the R206H mutation and who had baseline data in study PVO-1A-001.	0.00% 0/114 • Treatment-emergent adverse events are collected from first date of palovarotene intake up to end of 4-year follow-up period (approximately 57 months) for study PVO-1A-301. For study PVO-1A-001, adverse events (AEs) were collected from study day 1 up to approximately 37 months. While no pharmacological intervention was applied in this observational study (PVO-1A-001), safety issues resulting only from any study-related procedure were recorded as AEs. MedDRA version 21.0 for PVO-1A-001 study. The Safety analysis set included all enrolled participants who received at least 1 dose of palovarotene in study PVO-1A-301. The FAS included all participants in the Enrolled Analysis Set with FOP caused by the R206H mutation and who had baseline data in study PVO-1A-001.
Gastrointestinal disorders Nausea	8.4% 9/107 • Number of events 9 • Treatment-emergent adverse events are collected from first date of palovarotene intake up to end of 4-year follow-up period (approximately 57 months) for study PVO-1A-301. For study PVO-1A-001, adverse events (AEs) were collected from study day 1 up to approximately 37 months. While no pharmacological intervention was applied in this observational study (PVO-1A-001), safety issues resulting only from any study-related procedure were recorded as AEs. MedDRA version 21.0 for PVO-1A-001 study. The Safety analysis set included all enrolled participants who received at least 1 dose of palovarotene in study PVO-1A-301. The FAS included all participants in the Enrolled Analysis Set with FOP caused by the R206H mutation and who had baseline data in study PVO-1A-001.	3.7% 3/81 • Number of events 3 • Treatment-emergent adverse events are collected from first date of palovarotene intake up to end of 4-year follow-up period (approximately 57 months) for study PVO-1A-301. For study PVO-1A-001, adverse events (AEs) were collected from study day 1 up to approximately 37 months. While no pharmacological intervention was applied in this observational study (PVO-1A-001), safety issues resulting only from any study-related procedure were recorded as AEs. MedDRA version 21.0 for PVO-1A-001 study. The Safety analysis set included all enrolled participants who received at least 1 dose of palovarotene in study PVO-1A-301. The FAS included all participants in the Enrolled Analysis Set with FOP caused by the R206H mutation and who had baseline data in study PVO-1A-001.	0.00% 0/114 • Treatment-emergent adverse events are collected from first date of palovarotene intake up to end of 4-year follow-up period (approximately 57 months) for study PVO-1A-301. For study PVO-1A-001, adverse events (AEs) were collected from study day 1 up to approximately 37 months. While no pharmacological intervention was applied in this observational study (PVO-1A-001), safety issues resulting only from any study-related procedure were recorded as AEs. MedDRA version 21.0 for PVO-1A-001 study. The Safety analysis set included all enrolled participants who received at least 1 dose of palovarotene in study PVO-1A-301. The FAS included all participants in the Enrolled Analysis Set with FOP caused by the R206H mutation and who had baseline data in study PVO-1A-001.
Gastrointestinal disorders Cheilitis	2.8% 3/107 • Number of events 3 • Treatment-emergent adverse events are collected from first date of palovarotene intake up to end of 4-year follow-up period (approximately 57 months) for study PVO-1A-301. For study PVO-1A-001, adverse events (AEs) were collected from study day 1 up to approximately 37 months. While no pharmacological intervention was applied in this observational study (PVO-1A-001), safety issues resulting only from any study-related procedure were recorded as AEs. MedDRA version 21.0 for PVO-1A-001 study. The Safety analysis set included all enrolled participants who received at least 1 dose of palovarotene in study PVO-1A-301. The FAS included all participants in the Enrolled Analysis Set with FOP caused by the R206H mutation and who had baseline data in study PVO-1A-001.	9.9% 8/81 • Number of events 13 • Treatment-emergent adverse events are collected from first date of palovarotene intake up to end of 4-year follow-up period (approximately 57 months) for study PVO-1A-301. For study PVO-1A-001, adverse events (AEs) were collected from study day 1 up to approximately 37 months. While no pharmacological intervention was applied in this observational study (PVO-1A-001), safety issues resulting only from any study-related procedure were recorded as AEs. MedDRA version 21.0 for PVO-1A-001 study. The Safety analysis set included all enrolled participants who received at least 1 dose of palovarotene in study PVO-1A-301. The FAS included all participants in the Enrolled Analysis Set with FOP caused by the R206H mutation and who had baseline data in study PVO-1A-001.	0.00% 0/114 • Treatment-emergent adverse events are collected from first date of palovarotene intake up to end of 4-year follow-up period (approximately 57 months) for study PVO-1A-301. For study PVO-1A-001, adverse events (AEs) were collected from study day 1 up to approximately 37 months. While no pharmacological intervention was applied in this observational study (PVO-1A-001), safety issues resulting only from any study-related procedure were recorded as AEs. MedDRA version 21.0 for PVO-1A-001 study. The Safety analysis set included all enrolled participants who received at least 1 dose of palovarotene in study PVO-1A-301. The FAS included all participants in the Enrolled Analysis Set with FOP caused by the R206H mutation and who had baseline data in study PVO-1A-001.
Gastrointestinal disorders Diarrhea	5.6% 6/107 • Number of events 6 • Treatment-emergent adverse events are collected from first date of palovarotene intake up to end of 4-year follow-up period (approximately 57 months) for study PVO-1A-301. For study PVO-1A-001, adverse events (AEs) were collected from study day 1 up to approximately 37 months. While no pharmacological intervention was applied in this observational study (PVO-1A-001), safety issues resulting only from any study-related procedure were recorded as AEs. MedDRA version 21.0 for PVO-1A-001 study. The Safety analysis set included all enrolled participants who received at least 1 dose of palovarotene in study PVO-1A-301. The FAS included all participants in the Enrolled Analysis Set with FOP caused by the R206H mutation and who had baseline data in study PVO-1A-001.	2.5% 2/81 • Number of events 2 • Treatment-emergent adverse events are collected from first date of palovarotene intake up to end of 4-year follow-up period (approximately 57 months) for study PVO-1A-301. For study PVO-1A-001, adverse events (AEs) were collected from study day 1 up to approximately 37 months. While no pharmacological intervention was applied in this observational study (PVO-1A-001), safety issues resulting only from any study-related procedure were recorded as AEs. MedDRA version 21.0 for PVO-1A-001 study. The Safety analysis set included all enrolled participants who received at least 1 dose of palovarotene in study PVO-1A-301. The FAS included all participants in the Enrolled Analysis Set with FOP caused by the R206H mutation and who had baseline data in study PVO-1A-001.	0.00% 0/114 • Treatment-emergent adverse events are collected from first date of palovarotene intake up to end of 4-year follow-up period (approximately 57 months) for study PVO-1A-301. For study PVO-1A-001, adverse events (AEs) were collected from study day 1 up to approximately 37 months. While no pharmacological intervention was applied in this observational study (PVO-1A-001), safety issues resulting only from any study-related procedure were recorded as AEs. MedDRA version 21.0 for PVO-1A-001 study. The Safety analysis set included all enrolled participants who received at least 1 dose of palovarotene in study PVO-1A-301. The FAS included all participants in the Enrolled Analysis Set with FOP caused by the R206H mutation and who had baseline data in study PVO-1A-001.
Infections and infestations Upper Respiratory Tract Infection	21.5% 23/107 • Number of events 30 • Treatment-emergent adverse events are collected from first date of palovarotene intake up to end of 4-year follow-up period (approximately 57 months) for study PVO-1A-301. For study PVO-1A-001, adverse events (AEs) were collected from study day 1 up to approximately 37 months. While no pharmacological intervention was applied in this observational study (PVO-1A-001), safety issues resulting only from any study-related procedure were recorded as AEs. MedDRA version 21.0 for PVO-1A-001 study. The Safety analysis set included all enrolled participants who received at least 1 dose of palovarotene in study PVO-1A-301. The FAS included all participants in the Enrolled Analysis Set with FOP caused by the R206H mutation and who had baseline data in study PVO-1A-001.	7.4% 6/81 • Number of events 7 • Treatment-emergent adverse events are collected from first date of palovarotene intake up to end of 4-year follow-up period (approximately 57 months) for study PVO-1A-301. For study PVO-1A-001, adverse events (AEs) were collected from study day 1 up to approximately 37 months. While no pharmacological intervention was applied in this observational study (PVO-1A-001), safety issues resulting only from any study-related procedure were recorded as AEs. MedDRA version 21.0 for PVO-1A-001 study. The Safety analysis set included all enrolled participants who received at least 1 dose of palovarotene in study PVO-1A-301. The FAS included all participants in the Enrolled Analysis Set with FOP caused by the R206H mutation and who had baseline data in study PVO-1A-001.	0.00% 0/114 • Treatment-emergent adverse events are collected from first date of palovarotene intake up to end of 4-year follow-up period (approximately 57 months) for study PVO-1A-301. For study PVO-1A-001, adverse events (AEs) were collected from study day 1 up to approximately 37 months. While no pharmacological intervention was applied in this observational study (PVO-1A-001), safety issues resulting only from any study-related procedure were recorded as AEs. MedDRA version 21.0 for PVO-1A-001 study. The Safety analysis set included all enrolled participants who received at least 1 dose of palovarotene in study PVO-1A-301. The FAS included all participants in the Enrolled Analysis Set with FOP caused by the R206H mutation and who had baseline data in study PVO-1A-001.
Infections and infestations Nasopharyngitis	13.1% 14/107 • Number of events 26 • Treatment-emergent adverse events are collected from first date of palovarotene intake up to end of 4-year follow-up period (approximately 57 months) for study PVO-1A-301. For study PVO-1A-001, adverse events (AEs) were collected from study day 1 up to approximately 37 months. While no pharmacological intervention was applied in this observational study (PVO-1A-001), safety issues resulting only from any study-related procedure were recorded as AEs. MedDRA version 21.0 for PVO-1A-001 study. The Safety analysis set included all enrolled participants who received at least 1 dose of palovarotene in study PVO-1A-301. The FAS included all participants in the Enrolled Analysis Set with FOP caused by the R206H mutation and who had baseline data in study PVO-1A-001.	11.1% 9/81 • Number of events 12 • Treatment-emergent adverse events are collected from first date of palovarotene intake up to end of 4-year follow-up period (approximately 57 months) for study PVO-1A-301. For study PVO-1A-001, adverse events (AEs) were collected from study day 1 up to approximately 37 months. While no pharmacological intervention was applied in this observational study (PVO-1A-001), safety issues resulting only from any study-related procedure were recorded as AEs. MedDRA version 21.0 for PVO-1A-001 study. The Safety analysis set included all enrolled participants who received at least 1 dose of palovarotene in study PVO-1A-301. The FAS included all participants in the Enrolled Analysis Set with FOP caused by the R206H mutation and who had baseline data in study PVO-1A-001.	0.00% 0/114 • Treatment-emergent adverse events are collected from first date of palovarotene intake up to end of 4-year follow-up period (approximately 57 months) for study PVO-1A-301. For study PVO-1A-001, adverse events (AEs) were collected from study day 1 up to approximately 37 months. While no pharmacological intervention was applied in this observational study (PVO-1A-001), safety issues resulting only from any study-related procedure were recorded as AEs. MedDRA version 21.0 for PVO-1A-001 study. The Safety analysis set included all enrolled participants who received at least 1 dose of palovarotene in study PVO-1A-301. The FAS included all participants in the Enrolled Analysis Set with FOP caused by the R206H mutation and who had baseline data in study PVO-1A-001.
Infections and infestations Paronychia	8.4% 9/107 • Number of events 13 • Treatment-emergent adverse events are collected from first date of palovarotene intake up to end of 4-year follow-up period (approximately 57 months) for study PVO-1A-301. For study PVO-1A-001, adverse events (AEs) were collected from study day 1 up to approximately 37 months. While no pharmacological intervention was applied in this observational study (PVO-1A-001), safety issues resulting only from any study-related procedure were recorded as AEs. MedDRA version 21.0 for PVO-1A-001 study. The Safety analysis set included all enrolled participants who received at least 1 dose of palovarotene in study PVO-1A-301. The FAS included all participants in the Enrolled Analysis Set with FOP caused by the R206H mutation and who had baseline data in study PVO-1A-001.	12.3% 10/81 • Number of events 15 • Treatment-emergent adverse events are collected from first date of palovarotene intake up to end of 4-year follow-up period (approximately 57 months) for study PVO-1A-301. For study PVO-1A-001, adverse events (AEs) were collected from study day 1 up to approximately 37 months. While no pharmacological intervention was applied in this observational study (PVO-1A-001), safety issues resulting only from any study-related procedure were recorded as AEs. MedDRA version 21.0 for PVO-1A-001 study. The Safety analysis set included all enrolled participants who received at least 1 dose of palovarotene in study PVO-1A-301. The FAS included all participants in the Enrolled Analysis Set with FOP caused by the R206H mutation and who had baseline data in study PVO-1A-001.	0.00% 0/114 • Treatment-emergent adverse events are collected from first date of palovarotene intake up to end of 4-year follow-up period (approximately 57 months) for study PVO-1A-301. For study PVO-1A-001, adverse events (AEs) were collected from study day 1 up to approximately 37 months. While no pharmacological intervention was applied in this observational study (PVO-1A-001), safety issues resulting only from any study-related procedure were recorded as AEs. MedDRA version 21.0 for PVO-1A-001 study. The Safety analysis set included all enrolled participants who received at least 1 dose of palovarotene in study PVO-1A-301. The FAS included all participants in the Enrolled Analysis Set with FOP caused by the R206H mutation and who had baseline data in study PVO-1A-001.
Infections and infestations Ear Infection	4.7% 5/107 • Number of events 5 • Treatment-emergent adverse events are collected from first date of palovarotene intake up to end of 4-year follow-up period (approximately 57 months) for study PVO-1A-301. For study PVO-1A-001, adverse events (AEs) were collected from study day 1 up to approximately 37 months. While no pharmacological intervention was applied in this observational study (PVO-1A-001), safety issues resulting only from any study-related procedure were recorded as AEs. MedDRA version 21.0 for PVO-1A-001 study. The Safety analysis set included all enrolled participants who received at least 1 dose of palovarotene in study PVO-1A-301. The FAS included all participants in the Enrolled Analysis Set with FOP caused by the R206H mutation and who had baseline data in study PVO-1A-001.	7.4% 6/81 • Number of events 7 • Treatment-emergent adverse events are collected from first date of palovarotene intake up to end of 4-year follow-up period (approximately 57 months) for study PVO-1A-301. For study PVO-1A-001, adverse events (AEs) were collected from study day 1 up to approximately 37 months. While no pharmacological intervention was applied in this observational study (PVO-1A-001), safety issues resulting only from any study-related procedure were recorded as AEs. MedDRA version 21.0 for PVO-1A-001 study. The Safety analysis set included all enrolled participants who received at least 1 dose of palovarotene in study PVO-1A-301. The FAS included all participants in the Enrolled Analysis Set with FOP caused by the R206H mutation and who had baseline data in study PVO-1A-001.	0.00% 0/114 • Treatment-emergent adverse events are collected from first date of palovarotene intake up to end of 4-year follow-up period (approximately 57 months) for study PVO-1A-301. For study PVO-1A-001, adverse events (AEs) were collected from study day 1 up to approximately 37 months. While no pharmacological intervention was applied in this observational study (PVO-1A-001), safety issues resulting only from any study-related procedure were recorded as AEs. MedDRA version 21.0 for PVO-1A-001 study. The Safety analysis set included all enrolled participants who received at least 1 dose of palovarotene in study PVO-1A-301. The FAS included all participants in the Enrolled Analysis Set with FOP caused by the R206H mutation and who had baseline data in study PVO-1A-001.
Infections and infestations Otitis Media	5.6% 6/107 • Number of events 7 • Treatment-emergent adverse events are collected from first date of palovarotene intake up to end of 4-year follow-up period (approximately 57 months) for study PVO-1A-301. For study PVO-1A-001, adverse events (AEs) were collected from study day 1 up to approximately 37 months. While no pharmacological intervention was applied in this observational study (PVO-1A-001), safety issues resulting only from any study-related procedure were recorded as AEs. MedDRA version 21.0 for PVO-1A-001 study. The Safety analysis set included all enrolled participants who received at least 1 dose of palovarotene in study PVO-1A-301. The FAS included all participants in the Enrolled Analysis Set with FOP caused by the R206H mutation and who had baseline data in study PVO-1A-001.	3.7% 3/81 • Number of events 3 • Treatment-emergent adverse events are collected from first date of palovarotene intake up to end of 4-year follow-up period (approximately 57 months) for study PVO-1A-301. For study PVO-1A-001, adverse events (AEs) were collected from study day 1 up to approximately 37 months. While no pharmacological intervention was applied in this observational study (PVO-1A-001), safety issues resulting only from any study-related procedure were recorded as AEs. MedDRA version 21.0 for PVO-1A-001 study. The Safety analysis set included all enrolled participants who received at least 1 dose of palovarotene in study PVO-1A-301. The FAS included all participants in the Enrolled Analysis Set with FOP caused by the R206H mutation and who had baseline data in study PVO-1A-001.	0.00% 0/114 • Treatment-emergent adverse events are collected from first date of palovarotene intake up to end of 4-year follow-up period (approximately 57 months) for study PVO-1A-301. For study PVO-1A-001, adverse events (AEs) were collected from study day 1 up to approximately 37 months. While no pharmacological intervention was applied in this observational study (PVO-1A-001), safety issues resulting only from any study-related procedure were recorded as AEs. MedDRA version 21.0 for PVO-1A-001 study. The Safety analysis set included all enrolled participants who received at least 1 dose of palovarotene in study PVO-1A-301. The FAS included all participants in the Enrolled Analysis Set with FOP caused by the R206H mutation and who had baseline data in study PVO-1A-001.
Infections and infestations Gastroenteritis	5.6% 6/107 • Number of events 8 • Treatment-emergent adverse events are collected from first date of palovarotene intake up to end of 4-year follow-up period (approximately 57 months) for study PVO-1A-301. For study PVO-1A-001, adverse events (AEs) were collected from study day 1 up to approximately 37 months. While no pharmacological intervention was applied in this observational study (PVO-1A-001), safety issues resulting only from any study-related procedure were recorded as AEs. MedDRA version 21.0 for PVO-1A-001 study. The Safety analysis set included all enrolled participants who received at least 1 dose of palovarotene in study PVO-1A-301. The FAS included all participants in the Enrolled Analysis Set with FOP caused by the R206H mutation and who had baseline data in study PVO-1A-001.	2.5% 2/81 • Number of events 2 • Treatment-emergent adverse events are collected from first date of palovarotene intake up to end of 4-year follow-up period (approximately 57 months) for study PVO-1A-301. For study PVO-1A-001, adverse events (AEs) were collected from study day 1 up to approximately 37 months. While no pharmacological intervention was applied in this observational study (PVO-1A-001), safety issues resulting only from any study-related procedure were recorded as AEs. MedDRA version 21.0 for PVO-1A-001 study. The Safety analysis set included all enrolled participants who received at least 1 dose of palovarotene in study PVO-1A-301. The FAS included all participants in the Enrolled Analysis Set with FOP caused by the R206H mutation and who had baseline data in study PVO-1A-001.	0.00% 0/114 • Treatment-emergent adverse events are collected from first date of palovarotene intake up to end of 4-year follow-up period (approximately 57 months) for study PVO-1A-301. For study PVO-1A-001, adverse events (AEs) were collected from study day 1 up to approximately 37 months. While no pharmacological intervention was applied in this observational study (PVO-1A-001), safety issues resulting only from any study-related procedure were recorded as AEs. MedDRA version 21.0 for PVO-1A-001 study. The Safety analysis set included all enrolled participants who received at least 1 dose of palovarotene in study PVO-1A-301. The FAS included all participants in the Enrolled Analysis Set with FOP caused by the R206H mutation and who had baseline data in study PVO-1A-001.
Infections and infestations Urinary Tract Infection	5.6% 6/107 • Number of events 6 • Treatment-emergent adverse events are collected from first date of palovarotene intake up to end of 4-year follow-up period (approximately 57 months) for study PVO-1A-301. For study PVO-1A-001, adverse events (AEs) were collected from study day 1 up to approximately 37 months. While no pharmacological intervention was applied in this observational study (PVO-1A-001), safety issues resulting only from any study-related procedure were recorded as AEs. MedDRA version 21.0 for PVO-1A-001 study. The Safety analysis set included all enrolled participants who received at least 1 dose of palovarotene in study PVO-1A-301. The FAS included all participants in the Enrolled Analysis Set with FOP caused by the R206H mutation and who had baseline data in study PVO-1A-001.	1.2% 1/81 • Number of events 2 • Treatment-emergent adverse events are collected from first date of palovarotene intake up to end of 4-year follow-up period (approximately 57 months) for study PVO-1A-301. For study PVO-1A-001, adverse events (AEs) were collected from study day 1 up to approximately 37 months. While no pharmacological intervention was applied in this observational study (PVO-1A-001), safety issues resulting only from any study-related procedure were recorded as AEs. MedDRA version 21.0 for PVO-1A-001 study. The Safety analysis set included all enrolled participants who received at least 1 dose of palovarotene in study PVO-1A-301. The FAS included all participants in the Enrolled Analysis Set with FOP caused by the R206H mutation and who had baseline data in study PVO-1A-001.	0.00% 0/114 • Treatment-emergent adverse events are collected from first date of palovarotene intake up to end of 4-year follow-up period (approximately 57 months) for study PVO-1A-301. For study PVO-1A-001, adverse events (AEs) were collected from study day 1 up to approximately 37 months. While no pharmacological intervention was applied in this observational study (PVO-1A-001), safety issues resulting only from any study-related procedure were recorded as AEs. MedDRA version 21.0 for PVO-1A-001 study. The Safety analysis set included all enrolled participants who received at least 1 dose of palovarotene in study PVO-1A-301. The FAS included all participants in the Enrolled Analysis Set with FOP caused by the R206H mutation and who had baseline data in study PVO-1A-001.
Musculoskeletal and connective tissue disorders Arthralgia	29.9% 32/107 • Number of events 49 • Treatment-emergent adverse events are collected from first date of palovarotene intake up to end of 4-year follow-up period (approximately 57 months) for study PVO-1A-301. For study PVO-1A-001, adverse events (AEs) were collected from study day 1 up to approximately 37 months. While no pharmacological intervention was applied in this observational study (PVO-1A-001), safety issues resulting only from any study-related procedure were recorded as AEs. MedDRA version 21.0 for PVO-1A-001 study. The Safety analysis set included all enrolled participants who received at least 1 dose of palovarotene in study PVO-1A-301. The FAS included all participants in the Enrolled Analysis Set with FOP caused by the R206H mutation and who had baseline data in study PVO-1A-001.	18.5% 15/81 • Number of events 24 • Treatment-emergent adverse events are collected from first date of palovarotene intake up to end of 4-year follow-up period (approximately 57 months) for study PVO-1A-301. For study PVO-1A-001, adverse events (AEs) were collected from study day 1 up to approximately 37 months. While no pharmacological intervention was applied in this observational study (PVO-1A-001), safety issues resulting only from any study-related procedure were recorded as AEs. MedDRA version 21.0 for PVO-1A-001 study. The Safety analysis set included all enrolled participants who received at least 1 dose of palovarotene in study PVO-1A-301. The FAS included all participants in the Enrolled Analysis Set with FOP caused by the R206H mutation and who had baseline data in study PVO-1A-001.	0.00% 0/114 • Treatment-emergent adverse events are collected from first date of palovarotene intake up to end of 4-year follow-up period (approximately 57 months) for study PVO-1A-301. For study PVO-1A-001, adverse events (AEs) were collected from study day 1 up to approximately 37 months. While no pharmacological intervention was applied in this observational study (PVO-1A-001), safety issues resulting only from any study-related procedure were recorded as AEs. MedDRA version 21.0 for PVO-1A-001 study. The Safety analysis set included all enrolled participants who received at least 1 dose of palovarotene in study PVO-1A-301. The FAS included all participants in the Enrolled Analysis Set with FOP caused by the R206H mutation and who had baseline data in study PVO-1A-001.
Musculoskeletal and connective tissue disorders Pain In Extremity	19.6% 21/107 • Number of events 33 • Treatment-emergent adverse events are collected from first date of palovarotene intake up to end of 4-year follow-up period (approximately 57 months) for study PVO-1A-301. For study PVO-1A-001, adverse events (AEs) were collected from study day 1 up to approximately 37 months. While no pharmacological intervention was applied in this observational study (PVO-1A-001), safety issues resulting only from any study-related procedure were recorded as AEs. MedDRA version 21.0 for PVO-1A-001 study. The Safety analysis set included all enrolled participants who received at least 1 dose of palovarotene in study PVO-1A-301. The FAS included all participants in the Enrolled Analysis Set with FOP caused by the R206H mutation and who had baseline data in study PVO-1A-001.	11.1% 9/81 • Number of events 13 • Treatment-emergent adverse events are collected from first date of palovarotene intake up to end of 4-year follow-up period (approximately 57 months) for study PVO-1A-301. For study PVO-1A-001, adverse events (AEs) were collected from study day 1 up to approximately 37 months. While no pharmacological intervention was applied in this observational study (PVO-1A-001), safety issues resulting only from any study-related procedure were recorded as AEs. MedDRA version 21.0 for PVO-1A-001 study. The Safety analysis set included all enrolled participants who received at least 1 dose of palovarotene in study PVO-1A-301. The FAS included all participants in the Enrolled Analysis Set with FOP caused by the R206H mutation and who had baseline data in study PVO-1A-001.	0.00% 0/114 • Treatment-emergent adverse events are collected from first date of palovarotene intake up to end of 4-year follow-up period (approximately 57 months) for study PVO-1A-301. For study PVO-1A-001, adverse events (AEs) were collected from study day 1 up to approximately 37 months. While no pharmacological intervention was applied in this observational study (PVO-1A-001), safety issues resulting only from any study-related procedure were recorded as AEs. MedDRA version 21.0 for PVO-1A-001 study. The Safety analysis set included all enrolled participants who received at least 1 dose of palovarotene in study PVO-1A-301. The FAS included all participants in the Enrolled Analysis Set with FOP caused by the R206H mutation and who had baseline data in study PVO-1A-001.
Musculoskeletal and connective tissue disorders Neck Pain	5.6% 6/107 • Number of events 6 • Treatment-emergent adverse events are collected from first date of palovarotene intake up to end of 4-year follow-up period (approximately 57 months) for study PVO-1A-301. For study PVO-1A-001, adverse events (AEs) were collected from study day 1 up to approximately 37 months. While no pharmacological intervention was applied in this observational study (PVO-1A-001), safety issues resulting only from any study-related procedure were recorded as AEs. MedDRA version 21.0 for PVO-1A-001 study. The Safety analysis set included all enrolled participants who received at least 1 dose of palovarotene in study PVO-1A-301. The FAS included all participants in the Enrolled Analysis Set with FOP caused by the R206H mutation and who had baseline data in study PVO-1A-001.	7.4% 6/81 • Number of events 9 • Treatment-emergent adverse events are collected from first date of palovarotene intake up to end of 4-year follow-up period (approximately 57 months) for study PVO-1A-301. For study PVO-1A-001, adverse events (AEs) were collected from study day 1 up to approximately 37 months. While no pharmacological intervention was applied in this observational study (PVO-1A-001), safety issues resulting only from any study-related procedure were recorded as AEs. MedDRA version 21.0 for PVO-1A-001 study. The Safety analysis set included all enrolled participants who received at least 1 dose of palovarotene in study PVO-1A-301. The FAS included all participants in the Enrolled Analysis Set with FOP caused by the R206H mutation and who had baseline data in study PVO-1A-001.	0.00% 0/114 • Treatment-emergent adverse events are collected from first date of palovarotene intake up to end of 4-year follow-up period (approximately 57 months) for study PVO-1A-301. For study PVO-1A-001, adverse events (AEs) were collected from study day 1 up to approximately 37 months. While no pharmacological intervention was applied in this observational study (PVO-1A-001), safety issues resulting only from any study-related procedure were recorded as AEs. MedDRA version 21.0 for PVO-1A-001 study. The Safety analysis set included all enrolled participants who received at least 1 dose of palovarotene in study PVO-1A-301. The FAS included all participants in the Enrolled Analysis Set with FOP caused by the R206H mutation and who had baseline data in study PVO-1A-001.
Musculoskeletal and connective tissue disorders Back Pain	7.5% 8/107 • Number of events 13 • Treatment-emergent adverse events are collected from first date of palovarotene intake up to end of 4-year follow-up period (approximately 57 months) for study PVO-1A-301. For study PVO-1A-001, adverse events (AEs) were collected from study day 1 up to approximately 37 months. While no pharmacological intervention was applied in this observational study (PVO-1A-001), safety issues resulting only from any study-related procedure were recorded as AEs. MedDRA version 21.0 for PVO-1A-001 study. The Safety analysis set included all enrolled participants who received at least 1 dose of palovarotene in study PVO-1A-301. The FAS included all participants in the Enrolled Analysis Set with FOP caused by the R206H mutation and who had baseline data in study PVO-1A-001.	3.7% 3/81 • Number of events 4 • Treatment-emergent adverse events are collected from first date of palovarotene intake up to end of 4-year follow-up period (approximately 57 months) for study PVO-1A-301. For study PVO-1A-001, adverse events (AEs) were collected from study day 1 up to approximately 37 months. While no pharmacological intervention was applied in this observational study (PVO-1A-001), safety issues resulting only from any study-related procedure were recorded as AEs. MedDRA version 21.0 for PVO-1A-001 study. The Safety analysis set included all enrolled participants who received at least 1 dose of palovarotene in study PVO-1A-301. The FAS included all participants in the Enrolled Analysis Set with FOP caused by the R206H mutation and who had baseline data in study PVO-1A-001.	0.00% 0/114 • Treatment-emergent adverse events are collected from first date of palovarotene intake up to end of 4-year follow-up period (approximately 57 months) for study PVO-1A-301. For study PVO-1A-001, adverse events (AEs) were collected from study day 1 up to approximately 37 months. While no pharmacological intervention was applied in this observational study (PVO-1A-001), safety issues resulting only from any study-related procedure were recorded as AEs. MedDRA version 21.0 for PVO-1A-001 study. The Safety analysis set included all enrolled participants who received at least 1 dose of palovarotene in study PVO-1A-301. The FAS included all participants in the Enrolled Analysis Set with FOP caused by the R206H mutation and who had baseline data in study PVO-1A-001.
Musculoskeletal and connective tissue disorders Musculoskeletal Pain	6.5% 7/107 • Number of events 9 • Treatment-emergent adverse events are collected from first date of palovarotene intake up to end of 4-year follow-up period (approximately 57 months) for study PVO-1A-301. For study PVO-1A-001, adverse events (AEs) were collected from study day 1 up to approximately 37 months. While no pharmacological intervention was applied in this observational study (PVO-1A-001), safety issues resulting only from any study-related procedure were recorded as AEs. MedDRA version 21.0 for PVO-1A-001 study. The Safety analysis set included all enrolled participants who received at least 1 dose of palovarotene in study PVO-1A-301. The FAS included all participants in the Enrolled Analysis Set with FOP caused by the R206H mutation and who had baseline data in study PVO-1A-001.	6.2% 5/81 • Number of events 5 • Treatment-emergent adverse events are collected from first date of palovarotene intake up to end of 4-year follow-up period (approximately 57 months) for study PVO-1A-301. For study PVO-1A-001, adverse events (AEs) were collected from study day 1 up to approximately 37 months. While no pharmacological intervention was applied in this observational study (PVO-1A-001), safety issues resulting only from any study-related procedure were recorded as AEs. MedDRA version 21.0 for PVO-1A-001 study. The Safety analysis set included all enrolled participants who received at least 1 dose of palovarotene in study PVO-1A-301. The FAS included all participants in the Enrolled Analysis Set with FOP caused by the R206H mutation and who had baseline data in study PVO-1A-001.	0.00% 0/114 • Treatment-emergent adverse events are collected from first date of palovarotene intake up to end of 4-year follow-up period (approximately 57 months) for study PVO-1A-301. For study PVO-1A-001, adverse events (AEs) were collected from study day 1 up to approximately 37 months. While no pharmacological intervention was applied in this observational study (PVO-1A-001), safety issues resulting only from any study-related procedure were recorded as AEs. MedDRA version 21.0 for PVO-1A-001 study. The Safety analysis set included all enrolled participants who received at least 1 dose of palovarotene in study PVO-1A-301. The FAS included all participants in the Enrolled Analysis Set with FOP caused by the R206H mutation and who had baseline data in study PVO-1A-001.
Injury, poisoning and procedural complications Contusion	8.4% 9/107 • Number of events 12 • Treatment-emergent adverse events are collected from first date of palovarotene intake up to end of 4-year follow-up period (approximately 57 months) for study PVO-1A-301. For study PVO-1A-001, adverse events (AEs) were collected from study day 1 up to approximately 37 months. While no pharmacological intervention was applied in this observational study (PVO-1A-001), safety issues resulting only from any study-related procedure were recorded as AEs. MedDRA version 21.0 for PVO-1A-001 study. The Safety analysis set included all enrolled participants who received at least 1 dose of palovarotene in study PVO-1A-301. The FAS included all participants in the Enrolled Analysis Set with FOP caused by the R206H mutation and who had baseline data in study PVO-1A-001.	7.4% 6/81 • Number of events 6 • Treatment-emergent adverse events are collected from first date of palovarotene intake up to end of 4-year follow-up period (approximately 57 months) for study PVO-1A-301. For study PVO-1A-001, adverse events (AEs) were collected from study day 1 up to approximately 37 months. While no pharmacological intervention was applied in this observational study (PVO-1A-001), safety issues resulting only from any study-related procedure were recorded as AEs. MedDRA version 21.0 for PVO-1A-001 study. The Safety analysis set included all enrolled participants who received at least 1 dose of palovarotene in study PVO-1A-301. The FAS included all participants in the Enrolled Analysis Set with FOP caused by the R206H mutation and who had baseline data in study PVO-1A-001.	0.00% 0/114 • Treatment-emergent adverse events are collected from first date of palovarotene intake up to end of 4-year follow-up period (approximately 57 months) for study PVO-1A-301. For study PVO-1A-001, adverse events (AEs) were collected from study day 1 up to approximately 37 months. While no pharmacological intervention was applied in this observational study (PVO-1A-001), safety issues resulting only from any study-related procedure were recorded as AEs. MedDRA version 21.0 for PVO-1A-001 study. The Safety analysis set included all enrolled participants who received at least 1 dose of palovarotene in study PVO-1A-301. The FAS included all participants in the Enrolled Analysis Set with FOP caused by the R206H mutation and who had baseline data in study PVO-1A-001.
Injury, poisoning and procedural complications Skin Abrasion	7.5% 8/107 • Number of events 11 • Treatment-emergent adverse events are collected from first date of palovarotene intake up to end of 4-year follow-up period (approximately 57 months) for study PVO-1A-301. For study PVO-1A-001, adverse events (AEs) were collected from study day 1 up to approximately 37 months. While no pharmacological intervention was applied in this observational study (PVO-1A-001), safety issues resulting only from any study-related procedure were recorded as AEs. MedDRA version 21.0 for PVO-1A-001 study. The Safety analysis set included all enrolled participants who received at least 1 dose of palovarotene in study PVO-1A-301. The FAS included all participants in the Enrolled Analysis Set with FOP caused by the R206H mutation and who had baseline data in study PVO-1A-001.	11.1% 9/81 • Number of events 13 • Treatment-emergent adverse events are collected from first date of palovarotene intake up to end of 4-year follow-up period (approximately 57 months) for study PVO-1A-301. For study PVO-1A-001, adverse events (AEs) were collected from study day 1 up to approximately 37 months. While no pharmacological intervention was applied in this observational study (PVO-1A-001), safety issues resulting only from any study-related procedure were recorded as AEs. MedDRA version 21.0 for PVO-1A-001 study. The Safety analysis set included all enrolled participants who received at least 1 dose of palovarotene in study PVO-1A-301. The FAS included all participants in the Enrolled Analysis Set with FOP caused by the R206H mutation and who had baseline data in study PVO-1A-001.	0.00% 0/114 • Treatment-emergent adverse events are collected from first date of palovarotene intake up to end of 4-year follow-up period (approximately 57 months) for study PVO-1A-301. For study PVO-1A-001, adverse events (AEs) were collected from study day 1 up to approximately 37 months. While no pharmacological intervention was applied in this observational study (PVO-1A-001), safety issues resulting only from any study-related procedure were recorded as AEs. MedDRA version 21.0 for PVO-1A-001 study. The Safety analysis set included all enrolled participants who received at least 1 dose of palovarotene in study PVO-1A-301. The FAS included all participants in the Enrolled Analysis Set with FOP caused by the R206H mutation and who had baseline data in study PVO-1A-001.
Injury, poisoning and procedural complications Fall	9.3% 10/107 • Number of events 12 • Treatment-emergent adverse events are collected from first date of palovarotene intake up to end of 4-year follow-up period (approximately 57 months) for study PVO-1A-301. For study PVO-1A-001, adverse events (AEs) were collected from study day 1 up to approximately 37 months. While no pharmacological intervention was applied in this observational study (PVO-1A-001), safety issues resulting only from any study-related procedure were recorded as AEs. MedDRA version 21.0 for PVO-1A-001 study. The Safety analysis set included all enrolled participants who received at least 1 dose of palovarotene in study PVO-1A-301. The FAS included all participants in the Enrolled Analysis Set with FOP caused by the R206H mutation and who had baseline data in study PVO-1A-001.	8.6% 7/81 • Number of events 12 • Treatment-emergent adverse events are collected from first date of palovarotene intake up to end of 4-year follow-up period (approximately 57 months) for study PVO-1A-301. For study PVO-1A-001, adverse events (AEs) were collected from study day 1 up to approximately 37 months. While no pharmacological intervention was applied in this observational study (PVO-1A-001), safety issues resulting only from any study-related procedure were recorded as AEs. MedDRA version 21.0 for PVO-1A-001 study. The Safety analysis set included all enrolled participants who received at least 1 dose of palovarotene in study PVO-1A-301. The FAS included all participants in the Enrolled Analysis Set with FOP caused by the R206H mutation and who had baseline data in study PVO-1A-001.	0.00% 0/114 • Treatment-emergent adverse events are collected from first date of palovarotene intake up to end of 4-year follow-up period (approximately 57 months) for study PVO-1A-301. For study PVO-1A-001, adverse events (AEs) were collected from study day 1 up to approximately 37 months. While no pharmacological intervention was applied in this observational study (PVO-1A-001), safety issues resulting only from any study-related procedure were recorded as AEs. MedDRA version 21.0 for PVO-1A-001 study. The Safety analysis set included all enrolled participants who received at least 1 dose of palovarotene in study PVO-1A-301. The FAS included all participants in the Enrolled Analysis Set with FOP caused by the R206H mutation and who had baseline data in study PVO-1A-001.
Respiratory, thoracic and mediastinal disorders Cough	6.5% 7/107 • Number of events 7 • Treatment-emergent adverse events are collected from first date of palovarotene intake up to end of 4-year follow-up period (approximately 57 months) for study PVO-1A-301. For study PVO-1A-001, adverse events (AEs) were collected from study day 1 up to approximately 37 months. While no pharmacological intervention was applied in this observational study (PVO-1A-001), safety issues resulting only from any study-related procedure were recorded as AEs. MedDRA version 21.0 for PVO-1A-001 study. The Safety analysis set included all enrolled participants who received at least 1 dose of palovarotene in study PVO-1A-301. The FAS included all participants in the Enrolled Analysis Set with FOP caused by the R206H mutation and who had baseline data in study PVO-1A-001.	6.2% 5/81 • Number of events 5 • Treatment-emergent adverse events are collected from first date of palovarotene intake up to end of 4-year follow-up period (approximately 57 months) for study PVO-1A-301. For study PVO-1A-001, adverse events (AEs) were collected from study day 1 up to approximately 37 months. While no pharmacological intervention was applied in this observational study (PVO-1A-001), safety issues resulting only from any study-related procedure were recorded as AEs. MedDRA version 21.0 for PVO-1A-001 study. The Safety analysis set included all enrolled participants who received at least 1 dose of palovarotene in study PVO-1A-301. The FAS included all participants in the Enrolled Analysis Set with FOP caused by the R206H mutation and who had baseline data in study PVO-1A-001.	0.00% 0/114 • Treatment-emergent adverse events are collected from first date of palovarotene intake up to end of 4-year follow-up period (approximately 57 months) for study PVO-1A-301. For study PVO-1A-001, adverse events (AEs) were collected from study day 1 up to approximately 37 months. While no pharmacological intervention was applied in this observational study (PVO-1A-001), safety issues resulting only from any study-related procedure were recorded as AEs. MedDRA version 21.0 for PVO-1A-001 study. The Safety analysis set included all enrolled participants who received at least 1 dose of palovarotene in study PVO-1A-301. The FAS included all participants in the Enrolled Analysis Set with FOP caused by the R206H mutation and who had baseline data in study PVO-1A-001.
Respiratory, thoracic and mediastinal disorders Epistaxis	5.6% 6/107 • Number of events 14 • Treatment-emergent adverse events are collected from first date of palovarotene intake up to end of 4-year follow-up period (approximately 57 months) for study PVO-1A-301. For study PVO-1A-001, adverse events (AEs) were collected from study day 1 up to approximately 37 months. While no pharmacological intervention was applied in this observational study (PVO-1A-001), safety issues resulting only from any study-related procedure were recorded as AEs. MedDRA version 21.0 for PVO-1A-001 study. The Safety analysis set included all enrolled participants who received at least 1 dose of palovarotene in study PVO-1A-301. The FAS included all participants in the Enrolled Analysis Set with FOP caused by the R206H mutation and who had baseline data in study PVO-1A-001.	3.7% 3/81 • Number of events 3 • Treatment-emergent adverse events are collected from first date of palovarotene intake up to end of 4-year follow-up period (approximately 57 months) for study PVO-1A-301. For study PVO-1A-001, adverse events (AEs) were collected from study day 1 up to approximately 37 months. While no pharmacological intervention was applied in this observational study (PVO-1A-001), safety issues resulting only from any study-related procedure were recorded as AEs. MedDRA version 21.0 for PVO-1A-001 study. The Safety analysis set included all enrolled participants who received at least 1 dose of palovarotene in study PVO-1A-301. The FAS included all participants in the Enrolled Analysis Set with FOP caused by the R206H mutation and who had baseline data in study PVO-1A-001.	0.00% 0/114 • Treatment-emergent adverse events are collected from first date of palovarotene intake up to end of 4-year follow-up period (approximately 57 months) for study PVO-1A-301. For study PVO-1A-001, adverse events (AEs) were collected from study day 1 up to approximately 37 months. While no pharmacological intervention was applied in this observational study (PVO-1A-001), safety issues resulting only from any study-related procedure were recorded as AEs. MedDRA version 21.0 for PVO-1A-001 study. The Safety analysis set included all enrolled participants who received at least 1 dose of palovarotene in study PVO-1A-301. The FAS included all participants in the Enrolled Analysis Set with FOP caused by the R206H mutation and who had baseline data in study PVO-1A-001.
Eye disorders Dry Eye	7.5% 8/107 • Number of events 8 • Treatment-emergent adverse events are collected from first date of palovarotene intake up to end of 4-year follow-up period (approximately 57 months) for study PVO-1A-301. For study PVO-1A-001, adverse events (AEs) were collected from study day 1 up to approximately 37 months. While no pharmacological intervention was applied in this observational study (PVO-1A-001), safety issues resulting only from any study-related procedure were recorded as AEs. MedDRA version 21.0 for PVO-1A-001 study. The Safety analysis set included all enrolled participants who received at least 1 dose of palovarotene in study PVO-1A-301. The FAS included all participants in the Enrolled Analysis Set with FOP caused by the R206H mutation and who had baseline data in study PVO-1A-001.	13.6% 11/81 • Number of events 14 • Treatment-emergent adverse events are collected from first date of palovarotene intake up to end of 4-year follow-up period (approximately 57 months) for study PVO-1A-301. For study PVO-1A-001, adverse events (AEs) were collected from study day 1 up to approximately 37 months. While no pharmacological intervention was applied in this observational study (PVO-1A-001), safety issues resulting only from any study-related procedure were recorded as AEs. MedDRA version 21.0 for PVO-1A-001 study. The Safety analysis set included all enrolled participants who received at least 1 dose of palovarotene in study PVO-1A-301. The FAS included all participants in the Enrolled Analysis Set with FOP caused by the R206H mutation and who had baseline data in study PVO-1A-001.	0.00% 0/114 • Treatment-emergent adverse events are collected from first date of palovarotene intake up to end of 4-year follow-up period (approximately 57 months) for study PVO-1A-301. For study PVO-1A-001, adverse events (AEs) were collected from study day 1 up to approximately 37 months. While no pharmacological intervention was applied in this observational study (PVO-1A-001), safety issues resulting only from any study-related procedure were recorded as AEs. MedDRA version 21.0 for PVO-1A-001 study. The Safety analysis set included all enrolled participants who received at least 1 dose of palovarotene in study PVO-1A-301. The FAS included all participants in the Enrolled Analysis Set with FOP caused by the R206H mutation and who had baseline data in study PVO-1A-001.
Nervous system disorders Headache	9.3% 10/107 • Number of events 13 • Treatment-emergent adverse events are collected from first date of palovarotene intake up to end of 4-year follow-up period (approximately 57 months) for study PVO-1A-301. For study PVO-1A-001, adverse events (AEs) were collected from study day 1 up to approximately 37 months. While no pharmacological intervention was applied in this observational study (PVO-1A-001), safety issues resulting only from any study-related procedure were recorded as AEs. MedDRA version 21.0 for PVO-1A-001 study. The Safety analysis set included all enrolled participants who received at least 1 dose of palovarotene in study PVO-1A-301. The FAS included all participants in the Enrolled Analysis Set with FOP caused by the R206H mutation and who had baseline data in study PVO-1A-001.	8.6% 7/81 • Number of events 7 • Treatment-emergent adverse events are collected from first date of palovarotene intake up to end of 4-year follow-up period (approximately 57 months) for study PVO-1A-301. For study PVO-1A-001, adverse events (AEs) were collected from study day 1 up to approximately 37 months. While no pharmacological intervention was applied in this observational study (PVO-1A-001), safety issues resulting only from any study-related procedure were recorded as AEs. MedDRA version 21.0 for PVO-1A-001 study. The Safety analysis set included all enrolled participants who received at least 1 dose of palovarotene in study PVO-1A-301. The FAS included all participants in the Enrolled Analysis Set with FOP caused by the R206H mutation and who had baseline data in study PVO-1A-001.	0.00% 0/114 • Treatment-emergent adverse events are collected from first date of palovarotene intake up to end of 4-year follow-up period (approximately 57 months) for study PVO-1A-301. For study PVO-1A-001, adverse events (AEs) were collected from study day 1 up to approximately 37 months. While no pharmacological intervention was applied in this observational study (PVO-1A-001), safety issues resulting only from any study-related procedure were recorded as AEs. MedDRA version 21.0 for PVO-1A-001 study. The Safety analysis set included all enrolled participants who received at least 1 dose of palovarotene in study PVO-1A-301. The FAS included all participants in the Enrolled Analysis Set with FOP caused by the R206H mutation and who had baseline data in study PVO-1A-001.
Immune system disorders Seasonal Allergy	6.5% 7/107 • Number of events 8 • Treatment-emergent adverse events are collected from first date of palovarotene intake up to end of 4-year follow-up period (approximately 57 months) for study PVO-1A-301. For study PVO-1A-001, adverse events (AEs) were collected from study day 1 up to approximately 37 months. While no pharmacological intervention was applied in this observational study (PVO-1A-001), safety issues resulting only from any study-related procedure were recorded as AEs. MedDRA version 21.0 for PVO-1A-001 study. The Safety analysis set included all enrolled participants who received at least 1 dose of palovarotene in study PVO-1A-301. The FAS included all participants in the Enrolled Analysis Set with FOP caused by the R206H mutation and who had baseline data in study PVO-1A-001.	0.00% 0/81 • Treatment-emergent adverse events are collected from first date of palovarotene intake up to end of 4-year follow-up period (approximately 57 months) for study PVO-1A-301. For study PVO-1A-001, adverse events (AEs) were collected from study day 1 up to approximately 37 months. While no pharmacological intervention was applied in this observational study (PVO-1A-001), safety issues resulting only from any study-related procedure were recorded as AEs. MedDRA version 21.0 for PVO-1A-001 study. The Safety analysis set included all enrolled participants who received at least 1 dose of palovarotene in study PVO-1A-301. The FAS included all participants in the Enrolled Analysis Set with FOP caused by the R206H mutation and who had baseline data in study PVO-1A-001.	0.00% 0/114 • Treatment-emergent adverse events are collected from first date of palovarotene intake up to end of 4-year follow-up period (approximately 57 months) for study PVO-1A-301. For study PVO-1A-001, adverse events (AEs) were collected from study day 1 up to approximately 37 months. While no pharmacological intervention was applied in this observational study (PVO-1A-001), safety issues resulting only from any study-related procedure were recorded as AEs. MedDRA version 21.0 for PVO-1A-001 study. The Safety analysis set included all enrolled participants who received at least 1 dose of palovarotene in study PVO-1A-301. The FAS included all participants in the Enrolled Analysis Set with FOP caused by the R206H mutation and who had baseline data in study PVO-1A-001.
Skin and subcutaneous tissue disorders Ingrowing nail	5.6% 6/107 • Number of events 8 • Treatment-emergent adverse events are collected from first date of palovarotene intake up to end of 4-year follow-up period (approximately 57 months) for study PVO-1A-301. For study PVO-1A-001, adverse events (AEs) were collected from study day 1 up to approximately 37 months. While no pharmacological intervention was applied in this observational study (PVO-1A-001), safety issues resulting only from any study-related procedure were recorded as AEs. MedDRA version 21.0 for PVO-1A-001 study. The Safety analysis set included all enrolled participants who received at least 1 dose of palovarotene in study PVO-1A-301. The FAS included all participants in the Enrolled Analysis Set with FOP caused by the R206H mutation and who had baseline data in study PVO-1A-001.	4.9% 4/81 • Number of events 5 • Treatment-emergent adverse events are collected from first date of palovarotene intake up to end of 4-year follow-up period (approximately 57 months) for study PVO-1A-301. For study PVO-1A-001, adverse events (AEs) were collected from study day 1 up to approximately 37 months. While no pharmacological intervention was applied in this observational study (PVO-1A-001), safety issues resulting only from any study-related procedure were recorded as AEs. MedDRA version 21.0 for PVO-1A-001 study. The Safety analysis set included all enrolled participants who received at least 1 dose of palovarotene in study PVO-1A-301. The FAS included all participants in the Enrolled Analysis Set with FOP caused by the R206H mutation and who had baseline data in study PVO-1A-001.	0.00% 0/114 • Treatment-emergent adverse events are collected from first date of palovarotene intake up to end of 4-year follow-up period (approximately 57 months) for study PVO-1A-301. For study PVO-1A-001, adverse events (AEs) were collected from study day 1 up to approximately 37 months. While no pharmacological intervention was applied in this observational study (PVO-1A-001), safety issues resulting only from any study-related procedure were recorded as AEs. MedDRA version 21.0 for PVO-1A-001 study. The Safety analysis set included all enrolled participants who received at least 1 dose of palovarotene in study PVO-1A-301. The FAS included all participants in the Enrolled Analysis Set with FOP caused by the R206H mutation and who had baseline data in study PVO-1A-001.
Infections and infestations Influenza	6.5% 7/107 • Number of events 7 • Treatment-emergent adverse events are collected from first date of palovarotene intake up to end of 4-year follow-up period (approximately 57 months) for study PVO-1A-301. For study PVO-1A-001, adverse events (AEs) were collected from study day 1 up to approximately 37 months. While no pharmacological intervention was applied in this observational study (PVO-1A-001), safety issues resulting only from any study-related procedure were recorded as AEs. MedDRA version 21.0 for PVO-1A-001 study. The Safety analysis set included all enrolled participants who received at least 1 dose of palovarotene in study PVO-1A-301. The FAS included all participants in the Enrolled Analysis Set with FOP caused by the R206H mutation and who had baseline data in study PVO-1A-001.	4.9% 4/81 • Number of events 4 • Treatment-emergent adverse events are collected from first date of palovarotene intake up to end of 4-year follow-up period (approximately 57 months) for study PVO-1A-301. For study PVO-1A-001, adverse events (AEs) were collected from study day 1 up to approximately 37 months. While no pharmacological intervention was applied in this observational study (PVO-1A-001), safety issues resulting only from any study-related procedure were recorded as AEs. MedDRA version 21.0 for PVO-1A-001 study. The Safety analysis set included all enrolled participants who received at least 1 dose of palovarotene in study PVO-1A-301. The FAS included all participants in the Enrolled Analysis Set with FOP caused by the R206H mutation and who had baseline data in study PVO-1A-001.	0.00% 0/114 • Treatment-emergent adverse events are collected from first date of palovarotene intake up to end of 4-year follow-up period (approximately 57 months) for study PVO-1A-301. For study PVO-1A-001, adverse events (AEs) were collected from study day 1 up to approximately 37 months. While no pharmacological intervention was applied in this observational study (PVO-1A-001), safety issues resulting only from any study-related procedure were recorded as AEs. MedDRA version 21.0 for PVO-1A-001 study. The Safety analysis set included all enrolled participants who received at least 1 dose of palovarotene in study PVO-1A-301. The FAS included all participants in the Enrolled Analysis Set with FOP caused by the R206H mutation and who had baseline data in study PVO-1A-001.
Musculoskeletal and connective tissue disorders Joint range of motion decreased	5.6% 6/107 • Number of events 9 • Treatment-emergent adverse events are collected from first date of palovarotene intake up to end of 4-year follow-up period (approximately 57 months) for study PVO-1A-301. For study PVO-1A-001, adverse events (AEs) were collected from study day 1 up to approximately 37 months. While no pharmacological intervention was applied in this observational study (PVO-1A-001), safety issues resulting only from any study-related procedure were recorded as AEs. MedDRA version 21.0 for PVO-1A-001 study. The Safety analysis set included all enrolled participants who received at least 1 dose of palovarotene in study PVO-1A-301. The FAS included all participants in the Enrolled Analysis Set with FOP caused by the R206H mutation and who had baseline data in study PVO-1A-001.	3.7% 3/81 • Number of events 3 • Treatment-emergent adverse events are collected from first date of palovarotene intake up to end of 4-year follow-up period (approximately 57 months) for study PVO-1A-301. For study PVO-1A-001, adverse events (AEs) were collected from study day 1 up to approximately 37 months. While no pharmacological intervention was applied in this observational study (PVO-1A-001), safety issues resulting only from any study-related procedure were recorded as AEs. MedDRA version 21.0 for PVO-1A-001 study. The Safety analysis set included all enrolled participants who received at least 1 dose of palovarotene in study PVO-1A-301. The FAS included all participants in the Enrolled Analysis Set with FOP caused by the R206H mutation and who had baseline data in study PVO-1A-001.	0.00% 0/114 • Treatment-emergent adverse events are collected from first date of palovarotene intake up to end of 4-year follow-up period (approximately 57 months) for study PVO-1A-301. For study PVO-1A-001, adverse events (AEs) were collected from study day 1 up to approximately 37 months. While no pharmacological intervention was applied in this observational study (PVO-1A-001), safety issues resulting only from any study-related procedure were recorded as AEs. MedDRA version 21.0 for PVO-1A-001 study. The Safety analysis set included all enrolled participants who received at least 1 dose of palovarotene in study PVO-1A-301. The FAS included all participants in the Enrolled Analysis Set with FOP caused by the R206H mutation and who had baseline data in study PVO-1A-001.
Musculoskeletal and connective tissue disorders Pain in jaw	5.6% 6/107 • Number of events 7 • Treatment-emergent adverse events are collected from first date of palovarotene intake up to end of 4-year follow-up period (approximately 57 months) for study PVO-1A-301. For study PVO-1A-001, adverse events (AEs) were collected from study day 1 up to approximately 37 months. While no pharmacological intervention was applied in this observational study (PVO-1A-001), safety issues resulting only from any study-related procedure were recorded as AEs. MedDRA version 21.0 for PVO-1A-001 study. The Safety analysis set included all enrolled participants who received at least 1 dose of palovarotene in study PVO-1A-301. The FAS included all participants in the Enrolled Analysis Set with FOP caused by the R206H mutation and who had baseline data in study PVO-1A-001.	2.5% 2/81 • Number of events 2 • Treatment-emergent adverse events are collected from first date of palovarotene intake up to end of 4-year follow-up period (approximately 57 months) for study PVO-1A-301. For study PVO-1A-001, adverse events (AEs) were collected from study day 1 up to approximately 37 months. While no pharmacological intervention was applied in this observational study (PVO-1A-001), safety issues resulting only from any study-related procedure were recorded as AEs. MedDRA version 21.0 for PVO-1A-001 study. The Safety analysis set included all enrolled participants who received at least 1 dose of palovarotene in study PVO-1A-301. The FAS included all participants in the Enrolled Analysis Set with FOP caused by the R206H mutation and who had baseline data in study PVO-1A-001.	0.00% 0/114 • Treatment-emergent adverse events are collected from first date of palovarotene intake up to end of 4-year follow-up period (approximately 57 months) for study PVO-1A-301. For study PVO-1A-001, adverse events (AEs) were collected from study day 1 up to approximately 37 months. While no pharmacological intervention was applied in this observational study (PVO-1A-001), safety issues resulting only from any study-related procedure were recorded as AEs. MedDRA version 21.0 for PVO-1A-001 study. The Safety analysis set included all enrolled participants who received at least 1 dose of palovarotene in study PVO-1A-301. The FAS included all participants in the Enrolled Analysis Set with FOP caused by the R206H mutation and who had baseline data in study PVO-1A-001.
Musculoskeletal and connective tissue disorders Myalgia	5.6% 6/107 • Number of events 6 • Treatment-emergent adverse events are collected from first date of palovarotene intake up to end of 4-year follow-up period (approximately 57 months) for study PVO-1A-301. For study PVO-1A-001, adverse events (AEs) were collected from study day 1 up to approximately 37 months. While no pharmacological intervention was applied in this observational study (PVO-1A-001), safety issues resulting only from any study-related procedure were recorded as AEs. MedDRA version 21.0 for PVO-1A-001 study. The Safety analysis set included all enrolled participants who received at least 1 dose of palovarotene in study PVO-1A-301. The FAS included all participants in the Enrolled Analysis Set with FOP caused by the R206H mutation and who had baseline data in study PVO-1A-001.	2.5% 2/81 • Number of events 2 • Treatment-emergent adverse events are collected from first date of palovarotene intake up to end of 4-year follow-up period (approximately 57 months) for study PVO-1A-301. For study PVO-1A-001, adverse events (AEs) were collected from study day 1 up to approximately 37 months. While no pharmacological intervention was applied in this observational study (PVO-1A-001), safety issues resulting only from any study-related procedure were recorded as AEs. MedDRA version 21.0 for PVO-1A-001 study. The Safety analysis set included all enrolled participants who received at least 1 dose of palovarotene in study PVO-1A-301. The FAS included all participants in the Enrolled Analysis Set with FOP caused by the R206H mutation and who had baseline data in study PVO-1A-001.	0.00% 0/114 • Treatment-emergent adverse events are collected from first date of palovarotene intake up to end of 4-year follow-up period (approximately 57 months) for study PVO-1A-301. For study PVO-1A-001, adverse events (AEs) were collected from study day 1 up to approximately 37 months. While no pharmacological intervention was applied in this observational study (PVO-1A-001), safety issues resulting only from any study-related procedure were recorded as AEs. MedDRA version 21.0 for PVO-1A-001 study. The Safety analysis set included all enrolled participants who received at least 1 dose of palovarotene in study PVO-1A-301. The FAS included all participants in the Enrolled Analysis Set with FOP caused by the R206H mutation and who had baseline data in study PVO-1A-001.
General disorders Peripheral swelling	2.8% 3/107 • Number of events 3 • Treatment-emergent adverse events are collected from first date of palovarotene intake up to end of 4-year follow-up period (approximately 57 months) for study PVO-1A-301. For study PVO-1A-001, adverse events (AEs) were collected from study day 1 up to approximately 37 months. While no pharmacological intervention was applied in this observational study (PVO-1A-001), safety issues resulting only from any study-related procedure were recorded as AEs. MedDRA version 21.0 for PVO-1A-001 study. The Safety analysis set included all enrolled participants who received at least 1 dose of palovarotene in study PVO-1A-301. The FAS included all participants in the Enrolled Analysis Set with FOP caused by the R206H mutation and who had baseline data in study PVO-1A-001.	7.4% 6/81 • Number of events 7 • Treatment-emergent adverse events are collected from first date of palovarotene intake up to end of 4-year follow-up period (approximately 57 months) for study PVO-1A-301. For study PVO-1A-001, adverse events (AEs) were collected from study day 1 up to approximately 37 months. While no pharmacological intervention was applied in this observational study (PVO-1A-001), safety issues resulting only from any study-related procedure were recorded as AEs. MedDRA version 21.0 for PVO-1A-001 study. The Safety analysis set included all enrolled participants who received at least 1 dose of palovarotene in study PVO-1A-301. The FAS included all participants in the Enrolled Analysis Set with FOP caused by the R206H mutation and who had baseline data in study PVO-1A-001.	0.00% 0/114 • Treatment-emergent adverse events are collected from first date of palovarotene intake up to end of 4-year follow-up period (approximately 57 months) for study PVO-1A-301. For study PVO-1A-001, adverse events (AEs) were collected from study day 1 up to approximately 37 months. While no pharmacological intervention was applied in this observational study (PVO-1A-001), safety issues resulting only from any study-related procedure were recorded as AEs. MedDRA version 21.0 for PVO-1A-001 study. The Safety analysis set included all enrolled participants who received at least 1 dose of palovarotene in study PVO-1A-301. The FAS included all participants in the Enrolled Analysis Set with FOP caused by the R206H mutation and who had baseline data in study PVO-1A-001.
Investigations Bone density decreased	7.5% 8/107 • Number of events 8 • Treatment-emergent adverse events are collected from first date of palovarotene intake up to end of 4-year follow-up period (approximately 57 months) for study PVO-1A-301. For study PVO-1A-001, adverse events (AEs) were collected from study day 1 up to approximately 37 months. While no pharmacological intervention was applied in this observational study (PVO-1A-001), safety issues resulting only from any study-related procedure were recorded as AEs. MedDRA version 21.0 for PVO-1A-001 study. The Safety analysis set included all enrolled participants who received at least 1 dose of palovarotene in study PVO-1A-301. The FAS included all participants in the Enrolled Analysis Set with FOP caused by the R206H mutation and who had baseline data in study PVO-1A-001.	6.2% 5/81 • Number of events 5 • Treatment-emergent adverse events are collected from first date of palovarotene intake up to end of 4-year follow-up period (approximately 57 months) for study PVO-1A-301. For study PVO-1A-001, adverse events (AEs) were collected from study day 1 up to approximately 37 months. While no pharmacological intervention was applied in this observational study (PVO-1A-001), safety issues resulting only from any study-related procedure were recorded as AEs. MedDRA version 21.0 for PVO-1A-001 study. The Safety analysis set included all enrolled participants who received at least 1 dose of palovarotene in study PVO-1A-301. The FAS included all participants in the Enrolled Analysis Set with FOP caused by the R206H mutation and who had baseline data in study PVO-1A-001.	0.00% 0/114 • Treatment-emergent adverse events are collected from first date of palovarotene intake up to end of 4-year follow-up period (approximately 57 months) for study PVO-1A-301. For study PVO-1A-001, adverse events (AEs) were collected from study day 1 up to approximately 37 months. While no pharmacological intervention was applied in this observational study (PVO-1A-001), safety issues resulting only from any study-related procedure were recorded as AEs. MedDRA version 21.0 for PVO-1A-001 study. The Safety analysis set included all enrolled participants who received at least 1 dose of palovarotene in study PVO-1A-301. The FAS included all participants in the Enrolled Analysis Set with FOP caused by the R206H mutation and who had baseline data in study PVO-1A-001.
Investigations Alanine aminotransferase increased	0.93% 1/107 • Number of events 1 • Treatment-emergent adverse events are collected from first date of palovarotene intake up to end of 4-year follow-up period (approximately 57 months) for study PVO-1A-301. For study PVO-1A-001, adverse events (AEs) were collected from study day 1 up to approximately 37 months. While no pharmacological intervention was applied in this observational study (PVO-1A-001), safety issues resulting only from any study-related procedure were recorded as AEs. MedDRA version 21.0 for PVO-1A-001 study. The Safety analysis set included all enrolled participants who received at least 1 dose of palovarotene in study PVO-1A-301. The FAS included all participants in the Enrolled Analysis Set with FOP caused by the R206H mutation and who had baseline data in study PVO-1A-001.	6.2% 5/81 • Number of events 5 • Treatment-emergent adverse events are collected from first date of palovarotene intake up to end of 4-year follow-up period (approximately 57 months) for study PVO-1A-301. For study PVO-1A-001, adverse events (AEs) were collected from study day 1 up to approximately 37 months. While no pharmacological intervention was applied in this observational study (PVO-1A-001), safety issues resulting only from any study-related procedure were recorded as AEs. MedDRA version 21.0 for PVO-1A-001 study. The Safety analysis set included all enrolled participants who received at least 1 dose of palovarotene in study PVO-1A-301. The FAS included all participants in the Enrolled Analysis Set with FOP caused by the R206H mutation and who had baseline data in study PVO-1A-001.	0.00% 0/114 • Treatment-emergent adverse events are collected from first date of palovarotene intake up to end of 4-year follow-up period (approximately 57 months) for study PVO-1A-301. For study PVO-1A-001, adverse events (AEs) were collected from study day 1 up to approximately 37 months. While no pharmacological intervention was applied in this observational study (PVO-1A-001), safety issues resulting only from any study-related procedure were recorded as AEs. MedDRA version 21.0 for PVO-1A-001 study. The Safety analysis set included all enrolled participants who received at least 1 dose of palovarotene in study PVO-1A-301. The FAS included all participants in the Enrolled Analysis Set with FOP caused by the R206H mutation and who had baseline data in study PVO-1A-001.
Ear and labyrinth disorders Ear pain	5.6% 6/107 • Number of events 7 • Treatment-emergent adverse events are collected from first date of palovarotene intake up to end of 4-year follow-up period (approximately 57 months) for study PVO-1A-301. For study PVO-1A-001, adverse events (AEs) were collected from study day 1 up to approximately 37 months. While no pharmacological intervention was applied in this observational study (PVO-1A-001), safety issues resulting only from any study-related procedure were recorded as AEs. MedDRA version 21.0 for PVO-1A-001 study. The Safety analysis set included all enrolled participants who received at least 1 dose of palovarotene in study PVO-1A-301. The FAS included all participants in the Enrolled Analysis Set with FOP caused by the R206H mutation and who had baseline data in study PVO-1A-001.	1.2% 1/81 • Number of events 1 • Treatment-emergent adverse events are collected from first date of palovarotene intake up to end of 4-year follow-up period (approximately 57 months) for study PVO-1A-301. For study PVO-1A-001, adverse events (AEs) were collected from study day 1 up to approximately 37 months. While no pharmacological intervention was applied in this observational study (PVO-1A-001), safety issues resulting only from any study-related procedure were recorded as AEs. MedDRA version 21.0 for PVO-1A-001 study. The Safety analysis set included all enrolled participants who received at least 1 dose of palovarotene in study PVO-1A-301. The FAS included all participants in the Enrolled Analysis Set with FOP caused by the R206H mutation and who had baseline data in study PVO-1A-001.	0.00% 0/114 • Treatment-emergent adverse events are collected from first date of palovarotene intake up to end of 4-year follow-up period (approximately 57 months) for study PVO-1A-301. For study PVO-1A-001, adverse events (AEs) were collected from study day 1 up to approximately 37 months. While no pharmacological intervention was applied in this observational study (PVO-1A-001), safety issues resulting only from any study-related procedure were recorded as AEs. MedDRA version 21.0 for PVO-1A-001 study. The Safety analysis set included all enrolled participants who received at least 1 dose of palovarotene in study PVO-1A-301. The FAS included all participants in the Enrolled Analysis Set with FOP caused by the R206H mutation and who had baseline data in study PVO-1A-001.
Skin and subcutaneous tissue disorders Pruritus generalised	15.0% 16/107 • Number of events 21 • Treatment-emergent adverse events are collected from first date of palovarotene intake up to end of 4-year follow-up period (approximately 57 months) for study PVO-1A-301. For study PVO-1A-001, adverse events (AEs) were collected from study day 1 up to approximately 37 months. While no pharmacological intervention was applied in this observational study (PVO-1A-001), safety issues resulting only from any study-related procedure were recorded as AEs. MedDRA version 21.0 for PVO-1A-001 study. The Safety analysis set included all enrolled participants who received at least 1 dose of palovarotene in study PVO-1A-301. The FAS included all participants in the Enrolled Analysis Set with FOP caused by the R206H mutation and who had baseline data in study PVO-1A-001.	13.6% 11/81 • Number of events 19 • Treatment-emergent adverse events are collected from first date of palovarotene intake up to end of 4-year follow-up period (approximately 57 months) for study PVO-1A-301. For study PVO-1A-001, adverse events (AEs) were collected from study day 1 up to approximately 37 months. While no pharmacological intervention was applied in this observational study (PVO-1A-001), safety issues resulting only from any study-related procedure were recorded as AEs. MedDRA version 21.0 for PVO-1A-001 study. The Safety analysis set included all enrolled participants who received at least 1 dose of palovarotene in study PVO-1A-301. The FAS included all participants in the Enrolled Analysis Set with FOP caused by the R206H mutation and who had baseline data in study PVO-1A-001.	0.00% 0/114 • Treatment-emergent adverse events are collected from first date of palovarotene intake up to end of 4-year follow-up period (approximately 57 months) for study PVO-1A-301. For study PVO-1A-001, adverse events (AEs) were collected from study day 1 up to approximately 37 months. While no pharmacological intervention was applied in this observational study (PVO-1A-001), safety issues resulting only from any study-related procedure were recorded as AEs. MedDRA version 21.0 for PVO-1A-001 study. The Safety analysis set included all enrolled participants who received at least 1 dose of palovarotene in study PVO-1A-301. The FAS included all participants in the Enrolled Analysis Set with FOP caused by the R206H mutation and who had baseline data in study PVO-1A-001.

Additional Information

Medical Director

Ipsen

Phone: see email

Email: clinical.trials@ipsen.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place

Restriction type: OTHER