Trial Outcomes & Findings for APOLLO: The Study of an Investigational Drug, Patisiran (ALN-TTR02), for the Treatment of Transthyretin (TTR)-Mediated Amyloidosis (NCT NCT01960348)

NCT ID: NCT01960348

Last Updated: 2024-04-22

Results Overview

The difference between the patisiran (ALN-TTR02) and placebo groups in the change from baseline in mNIS+7 at 18 months. The mNIS+7 is a composite score that quantitates motor, sensory, and autonomic neurologic impairment due to injury of large and small nerves. The minimum and maximum values are 0 and 304, respectively. A higher score indicates a worse outcome.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

225 participants

Primary outcome timeframe

18mo

Results posted on

2024-04-22

Participant Flow

A total of 225 patients with hereditary transthyretin (hATTR) amyloidosis were enrolled and randomized in the study.

Participant milestones

Participant milestones
Measure	Patisiran (ALN-TTR02) All patients who received at least 1 dose of patisiran (ALN-TTR02)	Placebo All patients who received at least 1 dose of placebo
Overall Study STARTED	148	77
Overall Study COMPLETED	138	55
Overall Study NOT COMPLETED	10	22

Reasons for withdrawal

Reasons for withdrawal
Measure	Patisiran (ALN-TTR02) All patients who received at least 1 dose of patisiran (ALN-TTR02)	Placebo All patients who received at least 1 dose of placebo
Overall Study Adverse event, not serious	2	2
Overall Study Adverse event, serious fatal	6	5
Overall Study Adverse event, serious non-fatal	0	3
Overall Study Withdrawal by Subject	1	11
Overall Study Physician Decision	0	1
Overall Study Protocol Violation	1	0

Baseline Characteristics

APOLLO: The Study of an Investigational Drug, Patisiran (ALN-TTR02), for the Treatment of Transthyretin (TTR)-Mediated Amyloidosis

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Patisiran (ALN-TTR02) n=148 Participants All patients who received at least 1 dose of patisiran (ALN-TTR02)	Placebo n=77 Participants All patients who received at least 1 dose of placebo	Total n=225 Participants Total of all reporting groups
Age, Continuous	59.6 years STANDARD_DEVIATION 11.96 • n=5 Participants	62.2 years STANDARD_DEVIATION 10.76 • n=7 Participants	60.5 years STANDARD_DEVIATION 11.61 • n=5 Participants
Age, Customized <65 years	86 Participants n=5 Participants	44 Participants n=7 Participants	130 Participants n=5 Participants
Age, Customized 65-74 years	53 Participants n=5 Participants	24 Participants n=7 Participants	77 Participants n=5 Participants
Age, Customized ≥75 years	9 Participants n=5 Participants	9 Participants n=7 Participants	18 Participants n=5 Participants
Sex: Female, Male Female	39 Participants n=5 Participants	19 Participants n=7 Participants	58 Participants n=5 Participants
Sex: Female, Male Male	109 Participants n=5 Participants	58 Participants n=7 Participants	167 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	17 Participants n=5 Participants	11 Participants n=7 Participants	28 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	130 Participants n=5 Participants	65 Participants n=7 Participants	195 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	27 Participants n=5 Participants	25 Participants n=7 Participants	52 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	4 Participants n=5 Participants	1 Participants n=7 Participants	5 Participants n=5 Participants
Race (NIH/OMB) White	113 Participants n=5 Participants	50 Participants n=7 Participants	163 Participants n=5 Participants
Race (NIH/OMB) More than one race	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants
Baseline NIS NIS <50	62 Participants n=5 Participants	35 Participants n=7 Participants	97 Participants n=5 Participants
Baseline NIS NIS ≥50	86 Participants n=5 Participants	42 Participants n=7 Participants	128 Participants n=5 Participants
Genotype Class Early onset V30M (<50 years of age at onset)	13 Participants n=5 Participants	10 Participants n=7 Participants	23 Participants n=5 Participants
Genotype Class All other mutations (including late onset V30M)	135 Participants n=5 Participants	67 Participants n=7 Participants	202 Participants n=5 Participants
Previous Tetramer Stabilizer Use Yes	78 Participants n=5 Participants	41 Participants n=7 Participants	119 Participants n=5 Participants
Previous Tetramer Stabilizer Use No	70 Participants n=5 Participants	36 Participants n=7 Participants	106 Participants n=5 Participants
Baseline mNIS+7	80.93 Points STANDARD_DEVIATION 41.507 • n=5 Participants	74.61 Points STANDARD_DEVIATION 37.041 • n=7 Participants	78.77 Points STANDARD_DEVIATION 40.064 • n=5 Participants

PRIMARY outcome

Timeframe: 18mo

Population: Per protocol (PP) population: All randomized participants who received at least 1 dose of patisiran-LNP or placebo, completed baseline and the 18-month mNIS+7 assessments, and did not experience any major protocol deviations that may have impacted the efficacy results.

Outcome measures

Outcome measures
Measure	Patisiran (ALN-TTR02) n=137 Participants All patients who received at least 1 dose of patisiran (ALN-TTR02)	Placebo n=51 Participants All patients who received at least 1 dose of placebo
Modified Neuropathy Impairment Score +7 (mNIS+7)	-6.03 score on a scale Standard Error 1.739	27.96 score on a scale Standard Error 2.602

SECONDARY outcome

Timeframe: 18mo

Population: Per protocol (PP) population: All randomized participants who received at least 1 dose of patisiran-LNP or placebo, completed baseline and the 18-month Norfolk QoL-DN assessments, and did not experience any major protocol deviations that may have impacted the efficacy results.

The difference between the patisiran (ALN-TTR02) and placebo groups in the change from baseline in Norfolk QoL-DN at 18 months. The Norfolk QoL-DN questionnaire is a standardized 35-item patient-reported outcomes measure that is sensitive to the different features of diabetic neuropathy - small fiber, large fiber, and autonomic nerve function. The minimum and maximum values are -4 and 136, respectively. A higher score indicates a worse outcome.

Outcome measures

Outcome measures
Measure	Patisiran (ALN-TTR02) n=136 Participants All patients who received at least 1 dose of patisiran (ALN-TTR02)	Placebo n=48 Participants All patients who received at least 1 dose of placebo
Norfolk Quality of Life-Diabetic Neuropathy (Norfolk QoL-DN) Questionnaire	-6.7 score on a scale Standard Error 1.77	14.4 score on a scale Standard Error 2.73

SECONDARY outcome

Timeframe: 18mo

Population: Per protocol (PP) population: All randomized participants who received at least 1 dose of patisiran-LNP or placebo, completed baseline and the 18-month NIS-W assessments, and did not experience any major protocol deviations that may have impacted the efficacy results.

The difference between the patisiran (ALN-TTR02) and placebo groups in the change from baseline in NIS-W at 18 months. NIS-W is a measure of motor strength, comprised of cranial nerve and both upper and lower limb motor assessments. The minimum and maximum values are 0 and 192, respectively. A higher score indicates a worse outcome.

Outcome measures

Outcome measures
Measure	Patisiran (ALN-TTR02) n=137 Participants All patients who received at least 1 dose of patisiran (ALN-TTR02)	Placebo n=51 Participants All patients who received at least 1 dose of placebo
Neurological Impairment Score-Weakness (NIS-W) Score	0.05 score on a scale Standard Error 1.306	17.93 score on a scale Standard Error 1.959

SECONDARY outcome

Timeframe: 18mo

Population: Per protocol (PP) population: All randomized participants who received at least 1 dose of patisiran-LNP or placebo, completed baseline and either the 18-month R-ODS assessments, and did not experience any major protocol deviations that may have impacted the efficacy results.

The difference between the patisiran (ALN-TTR02) and placebo groups in the change from baseline in R-ODS score at 18 months. The R-ODS is comprised of a 24-item linearly weighted scale that specifically captures activity and social participation limitations in patients. The minimum and maximum values are 0 and 48, respectively. A higher score indicates a better outcome.

Outcome measures

Outcome measures
Measure	Patisiran (ALN-TTR02) n=138 Participants All patients who received at least 1 dose of patisiran (ALN-TTR02)	Placebo n=54 Participants All patients who received at least 1 dose of placebo
Rasch-built Overall Disability Scale (R-ODS) Score	0.0 score on a scale Standard Error 0.59	-8.9 score on a scale Standard Error 0.88

SECONDARY outcome

Timeframe: 18mo

Population: Per protocol (PP) population: All randomized participants who received at least 1 dose of patisiran-LNP or placebo, completed baseline and the 18-month 10-MWT assessments, and did not experience any major protocol deviations that may have impacted the efficacy results.

The difference between the patisiran (ALN-TTR02) and placebo groups in the change from baseline in 10-MWT at 18 months. Ability to ambulate (gait speed) was assessed through the 10-meter walk test (10-MWT). The walk had to be completed without assistance from another person; ambulatory aids such as canes and walkers were permitted.

Outcome measures

Outcome measures
Measure	Patisiran (ALN-TTR02) n=138 Participants All patients who received at least 1 dose of patisiran (ALN-TTR02)	Placebo n=55 Participants All patients who received at least 1 dose of placebo
Timed 10-meter Walk Test (10-MWT, Gait Speed)	0.077 m/sec Standard Error 0.0242	-0.235 m/sec Standard Error 0.0358

SECONDARY outcome

Timeframe: 18mo

Population: Per protocol (PP) population: All randomized participants who received at least 1 dose of patisiran-LNP or placebo, completed baseline and the 18-month mBMI assessments and did not experience any major protocol deviations that may have impacted the results..

The difference between the patisiran (ALN-TTR02) and placebo groups in the change from baseline in mBMI at 18 months. The nutritional status of patients was evaluated using the mBMI; calculated as the product of BMI (weight in kilograms divided by the square of height in meters) and serum albumin (g/L).

Outcome measures

Outcome measures
Measure	Patisiran (ALN-TTR02) n=133 Participants All patients who received at least 1 dose of patisiran (ALN-TTR02)	Placebo n=52 Participants All patients who received at least 1 dose of placebo
Modified Body Mass Index (mBMI)	-3.7 kg/m^2 × albumin g/L Standard Error 9.57	-119.4 kg/m^2 × albumin g/L Standard Error 14.51

SECONDARY outcome

Timeframe: 18mo

Population: Per protocol (PP) population: All randomized participants who received at least 1 dose of patisiran-LNP or placebo, completed baseline and the 18-month COMPASS 31 assessments, and did not experience any major protocol deviations that may have impacted the efficacy results.

The difference between the patisiran (ALN-TTR02) and placebo groups in the change from baseline in COMPASS 31 at 18 months. The COMPASS 31 is a measure of autonomic neuropathy symptoms. The questions evaluated 6 autonomic domains (orthostatic intolerance, vasomotor, secretomotor, gastrointestinal, bladder, and pupillomotor). The minimum and maximum values are 0 and 100, respectively. A higher score indicates a worse outcome.

Outcome measures

Outcome measures
Measure	Patisiran (ALN-TTR02) n=136 Participants All patients who received at least 1 dose of patisiran (ALN-TTR02)	Placebo n=53 Participants All patients who received at least 1 dose of placebo
Autonomic Symptoms Questionnaire (Composite Autonomic Symptom Score [COMPASS 31])	-5.29 score on a scale Standard Error 1.300	2.24 score on a scale Standard Error 1.940

Adverse Events

Patisiran (ALN-TTR02)

Serious events: 54 serious events

Other events: 143 other events

Deaths: 7 deaths

Placebo

Serious events: 31 serious events

Other events: 75 other events

Deaths: 6 deaths

Serious adverse events

Other adverse events

Additional Information

Chief Medical Officer

Alnylam Pharmaceuticals, Inc.

Phone: 866.330.0326

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60

Serious adverse events
Measure	Patisiran (ALN-TTR02) n=148 participants at risk All patients who received at least 1 dose of patisiran (ALN-TTR02)	Placebo n=77 participants at risk All patients who received at least 1 dose of placebo
Blood and lymphatic system disorders Anaemia	0.00% 0/148 • All Adverse Events (AEs) that occurred from start of study drug administration through End of Study (Day 567), or Follow-up (Day 602) if patient did not enter open-label extension study. AEs for patients with Rapid Disease Progression at Month 9 who stopped dosing were collected through Day 294 (42 days after last dose). The same event may appear as both an AE and a Serious Adverse Event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. Safety population: All participants who received at least 1 dose of patisiran-LNP or placebo. Participants were analyzed according to the treatment received.	1.3% 1/77 • Number of events 1 • All Adverse Events (AEs) that occurred from start of study drug administration through End of Study (Day 567), or Follow-up (Day 602) if patient did not enter open-label extension study. AEs for patients with Rapid Disease Progression at Month 9 who stopped dosing were collected through Day 294 (42 days after last dose). The same event may appear as both an AE and a Serious Adverse Event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. Safety population: All participants who received at least 1 dose of patisiran-LNP or placebo. Participants were analyzed according to the treatment received.
Blood and lymphatic system disorders Anaemia of chronic disease	0.68% 1/148 • Number of events 1 • All Adverse Events (AEs) that occurred from start of study drug administration through End of Study (Day 567), or Follow-up (Day 602) if patient did not enter open-label extension study. AEs for patients with Rapid Disease Progression at Month 9 who stopped dosing were collected through Day 294 (42 days after last dose). The same event may appear as both an AE and a Serious Adverse Event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. Safety population: All participants who received at least 1 dose of patisiran-LNP or placebo. Participants were analyzed according to the treatment received.	0.00% 0/77 • All Adverse Events (AEs) that occurred from start of study drug administration through End of Study (Day 567), or Follow-up (Day 602) if patient did not enter open-label extension study. AEs for patients with Rapid Disease Progression at Month 9 who stopped dosing were collected through Day 294 (42 days after last dose). The same event may appear as both an AE and a Serious Adverse Event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. Safety population: All participants who received at least 1 dose of patisiran-LNP or placebo. Participants were analyzed according to the treatment received.
Cardiac disorders Arteriosclerosis coronary artery	0.68% 1/148 • Number of events 1 • All Adverse Events (AEs) that occurred from start of study drug administration through End of Study (Day 567), or Follow-up (Day 602) if patient did not enter open-label extension study. AEs for patients with Rapid Disease Progression at Month 9 who stopped dosing were collected through Day 294 (42 days after last dose). The same event may appear as both an AE and a Serious Adverse Event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. Safety population: All participants who received at least 1 dose of patisiran-LNP or placebo. Participants were analyzed according to the treatment received.	0.00% 0/77 • All Adverse Events (AEs) that occurred from start of study drug administration through End of Study (Day 567), or Follow-up (Day 602) if patient did not enter open-label extension study. AEs for patients with Rapid Disease Progression at Month 9 who stopped dosing were collected through Day 294 (42 days after last dose). The same event may appear as both an AE and a Serious Adverse Event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. Safety population: All participants who received at least 1 dose of patisiran-LNP or placebo. Participants were analyzed according to the treatment received.
Cardiac disorders Atrial fibrillation	1.4% 2/148 • Number of events 2 • All Adverse Events (AEs) that occurred from start of study drug administration through End of Study (Day 567), or Follow-up (Day 602) if patient did not enter open-label extension study. AEs for patients with Rapid Disease Progression at Month 9 who stopped dosing were collected through Day 294 (42 days after last dose). The same event may appear as both an AE and a Serious Adverse Event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. Safety population: All participants who received at least 1 dose of patisiran-LNP or placebo. Participants were analyzed according to the treatment received.	1.3% 1/77 • Number of events 1 • All Adverse Events (AEs) that occurred from start of study drug administration through End of Study (Day 567), or Follow-up (Day 602) if patient did not enter open-label extension study. AEs for patients with Rapid Disease Progression at Month 9 who stopped dosing were collected through Day 294 (42 days after last dose). The same event may appear as both an AE and a Serious Adverse Event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. Safety population: All participants who received at least 1 dose of patisiran-LNP or placebo. Participants were analyzed according to the treatment received.
Cardiac disorders Atrioventricular block	0.68% 1/148 • Number of events 1 • All Adverse Events (AEs) that occurred from start of study drug administration through End of Study (Day 567), or Follow-up (Day 602) if patient did not enter open-label extension study. AEs for patients with Rapid Disease Progression at Month 9 who stopped dosing were collected through Day 294 (42 days after last dose). The same event may appear as both an AE and a Serious Adverse Event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. Safety population: All participants who received at least 1 dose of patisiran-LNP or placebo. Participants were analyzed according to the treatment received.	0.00% 0/77 • All Adverse Events (AEs) that occurred from start of study drug administration through End of Study (Day 567), or Follow-up (Day 602) if patient did not enter open-label extension study. AEs for patients with Rapid Disease Progression at Month 9 who stopped dosing were collected through Day 294 (42 days after last dose). The same event may appear as both an AE and a Serious Adverse Event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. Safety population: All participants who received at least 1 dose of patisiran-LNP or placebo. Participants were analyzed according to the treatment received.
Cardiac disorders Atrioventricular block complete	2.0% 3/148 • Number of events 3 • All Adverse Events (AEs) that occurred from start of study drug administration through End of Study (Day 567), or Follow-up (Day 602) if patient did not enter open-label extension study. AEs for patients with Rapid Disease Progression at Month 9 who stopped dosing were collected through Day 294 (42 days after last dose). The same event may appear as both an AE and a Serious Adverse Event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. Safety population: All participants who received at least 1 dose of patisiran-LNP or placebo. Participants were analyzed according to the treatment received.	0.00% 0/77 • All Adverse Events (AEs) that occurred from start of study drug administration through End of Study (Day 567), or Follow-up (Day 602) if patient did not enter open-label extension study. AEs for patients with Rapid Disease Progression at Month 9 who stopped dosing were collected through Day 294 (42 days after last dose). The same event may appear as both an AE and a Serious Adverse Event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. Safety population: All participants who received at least 1 dose of patisiran-LNP or placebo. Participants were analyzed according to the treatment received.
Cardiac disorders Cardiac amyloidosis	1.4% 2/148 • Number of events 2 • All Adverse Events (AEs) that occurred from start of study drug administration through End of Study (Day 567), or Follow-up (Day 602) if patient did not enter open-label extension study. AEs for patients with Rapid Disease Progression at Month 9 who stopped dosing were collected through Day 294 (42 days after last dose). The same event may appear as both an AE and a Serious Adverse Event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. Safety population: All participants who received at least 1 dose of patisiran-LNP or placebo. Participants were analyzed according to the treatment received.	1.3% 1/77 • Number of events 1 • All Adverse Events (AEs) that occurred from start of study drug administration through End of Study (Day 567), or Follow-up (Day 602) if patient did not enter open-label extension study. AEs for patients with Rapid Disease Progression at Month 9 who stopped dosing were collected through Day 294 (42 days after last dose). The same event may appear as both an AE and a Serious Adverse Event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. Safety population: All participants who received at least 1 dose of patisiran-LNP or placebo. Participants were analyzed according to the treatment received.
Cardiac disorders Cardiac arrest	1.4% 2/148 • Number of events 2 • All Adverse Events (AEs) that occurred from start of study drug administration through End of Study (Day 567), or Follow-up (Day 602) if patient did not enter open-label extension study. AEs for patients with Rapid Disease Progression at Month 9 who stopped dosing were collected through Day 294 (42 days after last dose). The same event may appear as both an AE and a Serious Adverse Event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. Safety population: All participants who received at least 1 dose of patisiran-LNP or placebo. Participants were analyzed according to the treatment received.	1.3% 1/77 • Number of events 1 • All Adverse Events (AEs) that occurred from start of study drug administration through End of Study (Day 567), or Follow-up (Day 602) if patient did not enter open-label extension study. AEs for patients with Rapid Disease Progression at Month 9 who stopped dosing were collected through Day 294 (42 days after last dose). The same event may appear as both an AE and a Serious Adverse Event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. Safety population: All participants who received at least 1 dose of patisiran-LNP or placebo. Participants were analyzed according to the treatment received.
Cardiac disorders Cardiac failure	2.0% 3/148 • Number of events 3 • All Adverse Events (AEs) that occurred from start of study drug administration through End of Study (Day 567), or Follow-up (Day 602) if patient did not enter open-label extension study. AEs for patients with Rapid Disease Progression at Month 9 who stopped dosing were collected through Day 294 (42 days after last dose). The same event may appear as both an AE and a Serious Adverse Event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. Safety population: All participants who received at least 1 dose of patisiran-LNP or placebo. Participants were analyzed according to the treatment received.	2.6% 2/77 • Number of events 2 • All Adverse Events (AEs) that occurred from start of study drug administration through End of Study (Day 567), or Follow-up (Day 602) if patient did not enter open-label extension study. AEs for patients with Rapid Disease Progression at Month 9 who stopped dosing were collected through Day 294 (42 days after last dose). The same event may appear as both an AE and a Serious Adverse Event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. Safety population: All participants who received at least 1 dose of patisiran-LNP or placebo. Participants were analyzed according to the treatment received.
Cardiac disorders Cardiac failure acute	0.00% 0/148 • All Adverse Events (AEs) that occurred from start of study drug administration through End of Study (Day 567), or Follow-up (Day 602) if patient did not enter open-label extension study. AEs for patients with Rapid Disease Progression at Month 9 who stopped dosing were collected through Day 294 (42 days after last dose). The same event may appear as both an AE and a Serious Adverse Event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. Safety population: All participants who received at least 1 dose of patisiran-LNP or placebo. Participants were analyzed according to the treatment received.	1.3% 1/77 • Number of events 2 • All Adverse Events (AEs) that occurred from start of study drug administration through End of Study (Day 567), or Follow-up (Day 602) if patient did not enter open-label extension study. AEs for patients with Rapid Disease Progression at Month 9 who stopped dosing were collected through Day 294 (42 days after last dose). The same event may appear as both an AE and a Serious Adverse Event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. Safety population: All participants who received at least 1 dose of patisiran-LNP or placebo. Participants were analyzed according to the treatment received.
Cardiac disorders Cardiac failure chronic	0.00% 0/148 • All Adverse Events (AEs) that occurred from start of study drug administration through End of Study (Day 567), or Follow-up (Day 602) if patient did not enter open-label extension study. AEs for patients with Rapid Disease Progression at Month 9 who stopped dosing were collected through Day 294 (42 days after last dose). The same event may appear as both an AE and a Serious Adverse Event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. Safety population: All participants who received at least 1 dose of patisiran-LNP or placebo. Participants were analyzed according to the treatment received.	1.3% 1/77 • Number of events 1 • All Adverse Events (AEs) that occurred from start of study drug administration through End of Study (Day 567), or Follow-up (Day 602) if patient did not enter open-label extension study. AEs for patients with Rapid Disease Progression at Month 9 who stopped dosing were collected through Day 294 (42 days after last dose). The same event may appear as both an AE and a Serious Adverse Event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. Safety population: All participants who received at least 1 dose of patisiran-LNP or placebo. Participants were analyzed according to the treatment received.
Cardiac disorders Cardiac failure congestive	2.0% 3/148 • Number of events 3 • All Adverse Events (AEs) that occurred from start of study drug administration through End of Study (Day 567), or Follow-up (Day 602) if patient did not enter open-label extension study. AEs for patients with Rapid Disease Progression at Month 9 who stopped dosing were collected through Day 294 (42 days after last dose). The same event may appear as both an AE and a Serious Adverse Event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. Safety population: All participants who received at least 1 dose of patisiran-LNP or placebo. Participants were analyzed according to the treatment received.	2.6% 2/77 • Number of events 3 • All Adverse Events (AEs) that occurred from start of study drug administration through End of Study (Day 567), or Follow-up (Day 602) if patient did not enter open-label extension study. AEs for patients with Rapid Disease Progression at Month 9 who stopped dosing were collected through Day 294 (42 days after last dose). The same event may appear as both an AE and a Serious Adverse Event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. Safety population: All participants who received at least 1 dose of patisiran-LNP or placebo. Participants were analyzed according to the treatment received.
Cardiac disorders Cardio-respiratory arrest	0.00% 0/148 • All Adverse Events (AEs) that occurred from start of study drug administration through End of Study (Day 567), or Follow-up (Day 602) if patient did not enter open-label extension study. AEs for patients with Rapid Disease Progression at Month 9 who stopped dosing were collected through Day 294 (42 days after last dose). The same event may appear as both an AE and a Serious Adverse Event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. Safety population: All participants who received at least 1 dose of patisiran-LNP or placebo. Participants were analyzed according to the treatment received.	1.3% 1/77 • Number of events 1 • All Adverse Events (AEs) that occurred from start of study drug administration through End of Study (Day 567), or Follow-up (Day 602) if patient did not enter open-label extension study. AEs for patients with Rapid Disease Progression at Month 9 who stopped dosing were collected through Day 294 (42 days after last dose). The same event may appear as both an AE and a Serious Adverse Event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. Safety population: All participants who received at least 1 dose of patisiran-LNP or placebo. Participants were analyzed according to the treatment received.
Cardiac disorders Cardiogenic shock	0.68% 1/148 • Number of events 1 • All Adverse Events (AEs) that occurred from start of study drug administration through End of Study (Day 567), or Follow-up (Day 602) if patient did not enter open-label extension study. AEs for patients with Rapid Disease Progression at Month 9 who stopped dosing were collected through Day 294 (42 days after last dose). The same event may appear as both an AE and a Serious Adverse Event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. Safety population: All participants who received at least 1 dose of patisiran-LNP or placebo. Participants were analyzed according to the treatment received.	0.00% 0/77 • All Adverse Events (AEs) that occurred from start of study drug administration through End of Study (Day 567), or Follow-up (Day 602) if patient did not enter open-label extension study. AEs for patients with Rapid Disease Progression at Month 9 who stopped dosing were collected through Day 294 (42 days after last dose). The same event may appear as both an AE and a Serious Adverse Event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. Safety population: All participants who received at least 1 dose of patisiran-LNP or placebo. Participants were analyzed according to the treatment received.
Cardiac disorders Cardiomyopathy	0.68% 1/148 • Number of events 1 • All Adverse Events (AEs) that occurred from start of study drug administration through End of Study (Day 567), or Follow-up (Day 602) if patient did not enter open-label extension study. AEs for patients with Rapid Disease Progression at Month 9 who stopped dosing were collected through Day 294 (42 days after last dose). The same event may appear as both an AE and a Serious Adverse Event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. Safety population: All participants who received at least 1 dose of patisiran-LNP or placebo. Participants were analyzed according to the treatment received.	0.00% 0/77 • All Adverse Events (AEs) that occurred from start of study drug administration through End of Study (Day 567), or Follow-up (Day 602) if patient did not enter open-label extension study. AEs for patients with Rapid Disease Progression at Month 9 who stopped dosing were collected through Day 294 (42 days after last dose). The same event may appear as both an AE and a Serious Adverse Event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. Safety population: All participants who received at least 1 dose of patisiran-LNP or placebo. Participants were analyzed according to the treatment received.
Cardiac disorders Conduction disorder	0.68% 1/148 • Number of events 1 • All Adverse Events (AEs) that occurred from start of study drug administration through End of Study (Day 567), or Follow-up (Day 602) if patient did not enter open-label extension study. AEs for patients with Rapid Disease Progression at Month 9 who stopped dosing were collected through Day 294 (42 days after last dose). The same event may appear as both an AE and a Serious Adverse Event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. Safety population: All participants who received at least 1 dose of patisiran-LNP or placebo. Participants were analyzed according to the treatment received.	1.3% 1/77 • Number of events 1 • All Adverse Events (AEs) that occurred from start of study drug administration through End of Study (Day 567), or Follow-up (Day 602) if patient did not enter open-label extension study. AEs for patients with Rapid Disease Progression at Month 9 who stopped dosing were collected through Day 294 (42 days after last dose). The same event may appear as both an AE and a Serious Adverse Event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. Safety population: All participants who received at least 1 dose of patisiran-LNP or placebo. Participants were analyzed according to the treatment received.
Cardiac disorders Pulseless electrical activity	0.68% 1/148 • Number of events 1 • All Adverse Events (AEs) that occurred from start of study drug administration through End of Study (Day 567), or Follow-up (Day 602) if patient did not enter open-label extension study. AEs for patients with Rapid Disease Progression at Month 9 who stopped dosing were collected through Day 294 (42 days after last dose). The same event may appear as both an AE and a Serious Adverse Event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. Safety population: All participants who received at least 1 dose of patisiran-LNP or placebo. Participants were analyzed according to the treatment received.	0.00% 0/77 • All Adverse Events (AEs) that occurred from start of study drug administration through End of Study (Day 567), or Follow-up (Day 602) if patient did not enter open-label extension study. AEs for patients with Rapid Disease Progression at Month 9 who stopped dosing were collected through Day 294 (42 days after last dose). The same event may appear as both an AE and a Serious Adverse Event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. Safety population: All participants who received at least 1 dose of patisiran-LNP or placebo. Participants were analyzed according to the treatment received.
Cardiac disorders Restrictive cardiomyopathy	0.00% 0/148 • All Adverse Events (AEs) that occurred from start of study drug administration through End of Study (Day 567), or Follow-up (Day 602) if patient did not enter open-label extension study. AEs for patients with Rapid Disease Progression at Month 9 who stopped dosing were collected through Day 294 (42 days after last dose). The same event may appear as both an AE and a Serious Adverse Event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. Safety population: All participants who received at least 1 dose of patisiran-LNP or placebo. Participants were analyzed according to the treatment received.	1.3% 1/77 • Number of events 1 • All Adverse Events (AEs) that occurred from start of study drug administration through End of Study (Day 567), or Follow-up (Day 602) if patient did not enter open-label extension study. AEs for patients with Rapid Disease Progression at Month 9 who stopped dosing were collected through Day 294 (42 days after last dose). The same event may appear as both an AE and a Serious Adverse Event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. Safety population: All participants who received at least 1 dose of patisiran-LNP or placebo. Participants were analyzed according to the treatment received.
Cardiac disorders Ventricular dyssynchrony	0.68% 1/148 • Number of events 1 • All Adverse Events (AEs) that occurred from start of study drug administration through End of Study (Day 567), or Follow-up (Day 602) if patient did not enter open-label extension study. AEs for patients with Rapid Disease Progression at Month 9 who stopped dosing were collected through Day 294 (42 days after last dose). The same event may appear as both an AE and a Serious Adverse Event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. Safety population: All participants who received at least 1 dose of patisiran-LNP or placebo. Participants were analyzed according to the treatment received.	0.00% 0/77 • All Adverse Events (AEs) that occurred from start of study drug administration through End of Study (Day 567), or Follow-up (Day 602) if patient did not enter open-label extension study. AEs for patients with Rapid Disease Progression at Month 9 who stopped dosing were collected through Day 294 (42 days after last dose). The same event may appear as both an AE and a Serious Adverse Event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. Safety population: All participants who received at least 1 dose of patisiran-LNP or placebo. Participants were analyzed according to the treatment received.
Cardiac disorders Ventricular fibrillation	0.68% 1/148 • Number of events 1 • All Adverse Events (AEs) that occurred from start of study drug administration through End of Study (Day 567), or Follow-up (Day 602) if patient did not enter open-label extension study. AEs for patients with Rapid Disease Progression at Month 9 who stopped dosing were collected through Day 294 (42 days after last dose). The same event may appear as both an AE and a Serious Adverse Event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. Safety population: All participants who received at least 1 dose of patisiran-LNP or placebo. Participants were analyzed according to the treatment received.	0.00% 0/77 • All Adverse Events (AEs) that occurred from start of study drug administration through End of Study (Day 567), or Follow-up (Day 602) if patient did not enter open-label extension study. AEs for patients with Rapid Disease Progression at Month 9 who stopped dosing were collected through Day 294 (42 days after last dose). The same event may appear as both an AE and a Serious Adverse Event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. Safety population: All participants who received at least 1 dose of patisiran-LNP or placebo. Participants were analyzed according to the treatment received.
Cardiac disorders Ventricular tachycardia	0.00% 0/148 • All Adverse Events (AEs) that occurred from start of study drug administration through End of Study (Day 567), or Follow-up (Day 602) if patient did not enter open-label extension study. AEs for patients with Rapid Disease Progression at Month 9 who stopped dosing were collected through Day 294 (42 days after last dose). The same event may appear as both an AE and a Serious Adverse Event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. Safety population: All participants who received at least 1 dose of patisiran-LNP or placebo. Participants were analyzed according to the treatment received.	1.3% 1/77 • Number of events 1 • All Adverse Events (AEs) that occurred from start of study drug administration through End of Study (Day 567), or Follow-up (Day 602) if patient did not enter open-label extension study. AEs for patients with Rapid Disease Progression at Month 9 who stopped dosing were collected through Day 294 (42 days after last dose). The same event may appear as both an AE and a Serious Adverse Event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. Safety population: All participants who received at least 1 dose of patisiran-LNP or placebo. Participants were analyzed according to the treatment received.
Congenital, familial and genetic disorders Hereditary neuropathic amyloidosis	0.00% 0/148 • All Adverse Events (AEs) that occurred from start of study drug administration through End of Study (Day 567), or Follow-up (Day 602) if patient did not enter open-label extension study. AEs for patients with Rapid Disease Progression at Month 9 who stopped dosing were collected through Day 294 (42 days after last dose). The same event may appear as both an AE and a Serious Adverse Event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. Safety population: All participants who received at least 1 dose of patisiran-LNP or placebo. Participants were analyzed according to the treatment received.	2.6% 2/77 • Number of events 2 • All Adverse Events (AEs) that occurred from start of study drug administration through End of Study (Day 567), or Follow-up (Day 602) if patient did not enter open-label extension study. AEs for patients with Rapid Disease Progression at Month 9 who stopped dosing were collected through Day 294 (42 days after last dose). The same event may appear as both an AE and a Serious Adverse Event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. Safety population: All participants who received at least 1 dose of patisiran-LNP or placebo. Participants were analyzed according to the treatment received.
Congenital, familial and genetic disorders Hypertrophic cardiomyopathy	0.00% 0/148 • All Adverse Events (AEs) that occurred from start of study drug administration through End of Study (Day 567), or Follow-up (Day 602) if patient did not enter open-label extension study. AEs for patients with Rapid Disease Progression at Month 9 who stopped dosing were collected through Day 294 (42 days after last dose). The same event may appear as both an AE and a Serious Adverse Event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. Safety population: All participants who received at least 1 dose of patisiran-LNP or placebo. Participants were analyzed according to the treatment received.	1.3% 1/77 • Number of events 1 • All Adverse Events (AEs) that occurred from start of study drug administration through End of Study (Day 567), or Follow-up (Day 602) if patient did not enter open-label extension study. AEs for patients with Rapid Disease Progression at Month 9 who stopped dosing were collected through Day 294 (42 days after last dose). The same event may appear as both an AE and a Serious Adverse Event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. Safety population: All participants who received at least 1 dose of patisiran-LNP or placebo. Participants were analyzed according to the treatment received.
Congenital, familial and genetic disorders Phimosis	0.68% 1/148 • Number of events 1 • All Adverse Events (AEs) that occurred from start of study drug administration through End of Study (Day 567), or Follow-up (Day 602) if patient did not enter open-label extension study. AEs for patients with Rapid Disease Progression at Month 9 who stopped dosing were collected through Day 294 (42 days after last dose). The same event may appear as both an AE and a Serious Adverse Event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. Safety population: All participants who received at least 1 dose of patisiran-LNP or placebo. Participants were analyzed according to the treatment received.	0.00% 0/77 • All Adverse Events (AEs) that occurred from start of study drug administration through End of Study (Day 567), or Follow-up (Day 602) if patient did not enter open-label extension study. AEs for patients with Rapid Disease Progression at Month 9 who stopped dosing were collected through Day 294 (42 days after last dose). The same event may appear as both an AE and a Serious Adverse Event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. Safety population: All participants who received at least 1 dose of patisiran-LNP or placebo. Participants were analyzed according to the treatment received.
Congenital, familial and genetic disorders Syringomyelia	0.68% 1/148 • Number of events 1 • All Adverse Events (AEs) that occurred from start of study drug administration through End of Study (Day 567), or Follow-up (Day 602) if patient did not enter open-label extension study. AEs for patients with Rapid Disease Progression at Month 9 who stopped dosing were collected through Day 294 (42 days after last dose). The same event may appear as both an AE and a Serious Adverse Event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. Safety population: All participants who received at least 1 dose of patisiran-LNP or placebo. Participants were analyzed according to the treatment received.	0.00% 0/77 • All Adverse Events (AEs) that occurred from start of study drug administration through End of Study (Day 567), or Follow-up (Day 602) if patient did not enter open-label extension study. AEs for patients with Rapid Disease Progression at Month 9 who stopped dosing were collected through Day 294 (42 days after last dose). The same event may appear as both an AE and a Serious Adverse Event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. Safety population: All participants who received at least 1 dose of patisiran-LNP or placebo. Participants were analyzed according to the treatment received.
Ear and labyrinth disorders Deafness unilateral	0.68% 1/148 • Number of events 1 • All Adverse Events (AEs) that occurred from start of study drug administration through End of Study (Day 567), or Follow-up (Day 602) if patient did not enter open-label extension study. AEs for patients with Rapid Disease Progression at Month 9 who stopped dosing were collected through Day 294 (42 days after last dose). The same event may appear as both an AE and a Serious Adverse Event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. Safety population: All participants who received at least 1 dose of patisiran-LNP or placebo. Participants were analyzed according to the treatment received.	0.00% 0/77 • All Adverse Events (AEs) that occurred from start of study drug administration through End of Study (Day 567), or Follow-up (Day 602) if patient did not enter open-label extension study. AEs for patients with Rapid Disease Progression at Month 9 who stopped dosing were collected through Day 294 (42 days after last dose). The same event may appear as both an AE and a Serious Adverse Event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. Safety population: All participants who received at least 1 dose of patisiran-LNP or placebo. Participants were analyzed according to the treatment received.
Ear and labyrinth disorders Vertigo	0.68% 1/148 • Number of events 1 • All Adverse Events (AEs) that occurred from start of study drug administration through End of Study (Day 567), or Follow-up (Day 602) if patient did not enter open-label extension study. AEs for patients with Rapid Disease Progression at Month 9 who stopped dosing were collected through Day 294 (42 days after last dose). The same event may appear as both an AE and a Serious Adverse Event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. Safety population: All participants who received at least 1 dose of patisiran-LNP or placebo. Participants were analyzed according to the treatment received.	0.00% 0/77 • All Adverse Events (AEs) that occurred from start of study drug administration through End of Study (Day 567), or Follow-up (Day 602) if patient did not enter open-label extension study. AEs for patients with Rapid Disease Progression at Month 9 who stopped dosing were collected through Day 294 (42 days after last dose). The same event may appear as both an AE and a Serious Adverse Event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. Safety population: All participants who received at least 1 dose of patisiran-LNP or placebo. Participants were analyzed according to the treatment received.
Eye disorders Maculopathy	0.68% 1/148 • Number of events 1 • All Adverse Events (AEs) that occurred from start of study drug administration through End of Study (Day 567), or Follow-up (Day 602) if patient did not enter open-label extension study. AEs for patients with Rapid Disease Progression at Month 9 who stopped dosing were collected through Day 294 (42 days after last dose). The same event may appear as both an AE and a Serious Adverse Event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. Safety population: All participants who received at least 1 dose of patisiran-LNP or placebo. Participants were analyzed according to the treatment received.	0.00% 0/77 • All Adverse Events (AEs) that occurred from start of study drug administration through End of Study (Day 567), or Follow-up (Day 602) if patient did not enter open-label extension study. AEs for patients with Rapid Disease Progression at Month 9 who stopped dosing were collected through Day 294 (42 days after last dose). The same event may appear as both an AE and a Serious Adverse Event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. Safety population: All participants who received at least 1 dose of patisiran-LNP or placebo. Participants were analyzed according to the treatment received.
Eye disorders Vitreous haemorrhage	0.68% 1/148 • Number of events 1 • All Adverse Events (AEs) that occurred from start of study drug administration through End of Study (Day 567), or Follow-up (Day 602) if patient did not enter open-label extension study. AEs for patients with Rapid Disease Progression at Month 9 who stopped dosing were collected through Day 294 (42 days after last dose). The same event may appear as both an AE and a Serious Adverse Event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. Safety population: All participants who received at least 1 dose of patisiran-LNP or placebo. Participants were analyzed according to the treatment received.	0.00% 0/77 • All Adverse Events (AEs) that occurred from start of study drug administration through End of Study (Day 567), or Follow-up (Day 602) if patient did not enter open-label extension study. AEs for patients with Rapid Disease Progression at Month 9 who stopped dosing were collected through Day 294 (42 days after last dose). The same event may appear as both an AE and a Serious Adverse Event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. Safety population: All participants who received at least 1 dose of patisiran-LNP or placebo. Participants were analyzed according to the treatment received.
Eye disorders Vitreous opacities	0.68% 1/148 • Number of events 1 • All Adverse Events (AEs) that occurred from start of study drug administration through End of Study (Day 567), or Follow-up (Day 602) if patient did not enter open-label extension study. AEs for patients with Rapid Disease Progression at Month 9 who stopped dosing were collected through Day 294 (42 days after last dose). The same event may appear as both an AE and a Serious Adverse Event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. Safety population: All participants who received at least 1 dose of patisiran-LNP or placebo. Participants were analyzed according to the treatment received.	0.00% 0/77 • All Adverse Events (AEs) that occurred from start of study drug administration through End of Study (Day 567), or Follow-up (Day 602) if patient did not enter open-label extension study. AEs for patients with Rapid Disease Progression at Month 9 who stopped dosing were collected through Day 294 (42 days after last dose). The same event may appear as both an AE and a Serious Adverse Event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. Safety population: All participants who received at least 1 dose of patisiran-LNP or placebo. Participants were analyzed according to the treatment received.
Gastrointestinal disorders Ascites	0.68% 1/148 • Number of events 1 • All Adverse Events (AEs) that occurred from start of study drug administration through End of Study (Day 567), or Follow-up (Day 602) if patient did not enter open-label extension study. AEs for patients with Rapid Disease Progression at Month 9 who stopped dosing were collected through Day 294 (42 days after last dose). The same event may appear as both an AE and a Serious Adverse Event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. Safety population: All participants who received at least 1 dose of patisiran-LNP or placebo. Participants were analyzed according to the treatment received.	0.00% 0/77 • All Adverse Events (AEs) that occurred from start of study drug administration through End of Study (Day 567), or Follow-up (Day 602) if patient did not enter open-label extension study. AEs for patients with Rapid Disease Progression at Month 9 who stopped dosing were collected through Day 294 (42 days after last dose). The same event may appear as both an AE and a Serious Adverse Event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. Safety population: All participants who received at least 1 dose of patisiran-LNP or placebo. Participants were analyzed according to the treatment received.
Gastrointestinal disorders Constipation	0.00% 0/148 • All Adverse Events (AEs) that occurred from start of study drug administration through End of Study (Day 567), or Follow-up (Day 602) if patient did not enter open-label extension study. AEs for patients with Rapid Disease Progression at Month 9 who stopped dosing were collected through Day 294 (42 days after last dose). The same event may appear as both an AE and a Serious Adverse Event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. Safety population: All participants who received at least 1 dose of patisiran-LNP or placebo. Participants were analyzed according to the treatment received.	2.6% 2/77 • Number of events 2 • All Adverse Events (AEs) that occurred from start of study drug administration through End of Study (Day 567), or Follow-up (Day 602) if patient did not enter open-label extension study. AEs for patients with Rapid Disease Progression at Month 9 who stopped dosing were collected through Day 294 (42 days after last dose). The same event may appear as both an AE and a Serious Adverse Event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. Safety population: All participants who received at least 1 dose of patisiran-LNP or placebo. Participants were analyzed according to the treatment received.
Gastrointestinal disorders Diarrhoea	5.4% 8/148 • Number of events 9 • All Adverse Events (AEs) that occurred from start of study drug administration through End of Study (Day 567), or Follow-up (Day 602) if patient did not enter open-label extension study. AEs for patients with Rapid Disease Progression at Month 9 who stopped dosing were collected through Day 294 (42 days after last dose). The same event may appear as both an AE and a Serious Adverse Event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. Safety population: All participants who received at least 1 dose of patisiran-LNP or placebo. Participants were analyzed according to the treatment received.	1.3% 1/77 • Number of events 1 • All Adverse Events (AEs) that occurred from start of study drug administration through End of Study (Day 567), or Follow-up (Day 602) if patient did not enter open-label extension study. AEs for patients with Rapid Disease Progression at Month 9 who stopped dosing were collected through Day 294 (42 days after last dose). The same event may appear as both an AE and a Serious Adverse Event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. Safety population: All participants who received at least 1 dose of patisiran-LNP or placebo. Participants were analyzed according to the treatment received.
Gastrointestinal disorders Gastritis	0.00% 0/148 • All Adverse Events (AEs) that occurred from start of study drug administration through End of Study (Day 567), or Follow-up (Day 602) if patient did not enter open-label extension study. AEs for patients with Rapid Disease Progression at Month 9 who stopped dosing were collected through Day 294 (42 days after last dose). The same event may appear as both an AE and a Serious Adverse Event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. Safety population: All participants who received at least 1 dose of patisiran-LNP or placebo. Participants were analyzed according to the treatment received.	1.3% 1/77 • Number of events 1 • All Adverse Events (AEs) that occurred from start of study drug administration through End of Study (Day 567), or Follow-up (Day 602) if patient did not enter open-label extension study. AEs for patients with Rapid Disease Progression at Month 9 who stopped dosing were collected through Day 294 (42 days after last dose). The same event may appear as both an AE and a Serious Adverse Event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. Safety population: All participants who received at least 1 dose of patisiran-LNP or placebo. Participants were analyzed according to the treatment received.
Gastrointestinal disorders Gastrointestinal haemorrhage	0.00% 0/148 • All Adverse Events (AEs) that occurred from start of study drug administration through End of Study (Day 567), or Follow-up (Day 602) if patient did not enter open-label extension study. AEs for patients with Rapid Disease Progression at Month 9 who stopped dosing were collected through Day 294 (42 days after last dose). The same event may appear as both an AE and a Serious Adverse Event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. Safety population: All participants who received at least 1 dose of patisiran-LNP or placebo. Participants were analyzed according to the treatment received.	1.3% 1/77 • Number of events 1 • All Adverse Events (AEs) that occurred from start of study drug administration through End of Study (Day 567), or Follow-up (Day 602) if patient did not enter open-label extension study. AEs for patients with Rapid Disease Progression at Month 9 who stopped dosing were collected through Day 294 (42 days after last dose). The same event may appear as both an AE and a Serious Adverse Event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. Safety population: All participants who received at least 1 dose of patisiran-LNP or placebo. Participants were analyzed according to the treatment received.
Gastrointestinal disorders Gastrointestinal motility disorder	0.68% 1/148 • Number of events 1 • All Adverse Events (AEs) that occurred from start of study drug administration through End of Study (Day 567), or Follow-up (Day 602) if patient did not enter open-label extension study. AEs for patients with Rapid Disease Progression at Month 9 who stopped dosing were collected through Day 294 (42 days after last dose). The same event may appear as both an AE and a Serious Adverse Event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. Safety population: All participants who received at least 1 dose of patisiran-LNP or placebo. Participants were analyzed according to the treatment received.	0.00% 0/77 • All Adverse Events (AEs) that occurred from start of study drug administration through End of Study (Day 567), or Follow-up (Day 602) if patient did not enter open-label extension study. AEs for patients with Rapid Disease Progression at Month 9 who stopped dosing were collected through Day 294 (42 days after last dose). The same event may appear as both an AE and a Serious Adverse Event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. Safety population: All participants who received at least 1 dose of patisiran-LNP or placebo. Participants were analyzed according to the treatment received.
Gastrointestinal disorders Hiatus hernia	0.68% 1/148 • Number of events 1 • All Adverse Events (AEs) that occurred from start of study drug administration through End of Study (Day 567), or Follow-up (Day 602) if patient did not enter open-label extension study. AEs for patients with Rapid Disease Progression at Month 9 who stopped dosing were collected through Day 294 (42 days after last dose). The same event may appear as both an AE and a Serious Adverse Event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. Safety population: All participants who received at least 1 dose of patisiran-LNP or placebo. Participants were analyzed according to the treatment received.	0.00% 0/77 • All Adverse Events (AEs) that occurred from start of study drug administration through End of Study (Day 567), or Follow-up (Day 602) if patient did not enter open-label extension study. AEs for patients with Rapid Disease Progression at Month 9 who stopped dosing were collected through Day 294 (42 days after last dose). The same event may appear as both an AE and a Serious Adverse Event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. Safety population: All participants who received at least 1 dose of patisiran-LNP or placebo. Participants were analyzed according to the treatment received.
Gastrointestinal disorders Impaired gastric emptying	0.68% 1/148 • Number of events 1 • All Adverse Events (AEs) that occurred from start of study drug administration through End of Study (Day 567), or Follow-up (Day 602) if patient did not enter open-label extension study. AEs for patients with Rapid Disease Progression at Month 9 who stopped dosing were collected through Day 294 (42 days after last dose). The same event may appear as both an AE and a Serious Adverse Event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. Safety population: All participants who received at least 1 dose of patisiran-LNP or placebo. Participants were analyzed according to the treatment received.	0.00% 0/77 • All Adverse Events (AEs) that occurred from start of study drug administration through End of Study (Day 567), or Follow-up (Day 602) if patient did not enter open-label extension study. AEs for patients with Rapid Disease Progression at Month 9 who stopped dosing were collected through Day 294 (42 days after last dose). The same event may appear as both an AE and a Serious Adverse Event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. Safety population: All participants who received at least 1 dose of patisiran-LNP or placebo. Participants were analyzed according to the treatment received.
Gastrointestinal disorders Large intestine polyp	0.00% 0/148 • All Adverse Events (AEs) that occurred from start of study drug administration through End of Study (Day 567), or Follow-up (Day 602) if patient did not enter open-label extension study. AEs for patients with Rapid Disease Progression at Month 9 who stopped dosing were collected through Day 294 (42 days after last dose). The same event may appear as both an AE and a Serious Adverse Event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. Safety population: All participants who received at least 1 dose of patisiran-LNP or placebo. Participants were analyzed according to the treatment received.	1.3% 1/77 • Number of events 1 • All Adverse Events (AEs) that occurred from start of study drug administration through End of Study (Day 567), or Follow-up (Day 602) if patient did not enter open-label extension study. AEs for patients with Rapid Disease Progression at Month 9 who stopped dosing were collected through Day 294 (42 days after last dose). The same event may appear as both an AE and a Serious Adverse Event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. Safety population: All participants who received at least 1 dose of patisiran-LNP or placebo. Participants were analyzed according to the treatment received.
Gastrointestinal disorders Oesophagitis	0.00% 0/148 • All Adverse Events (AEs) that occurred from start of study drug administration through End of Study (Day 567), or Follow-up (Day 602) if patient did not enter open-label extension study. AEs for patients with Rapid Disease Progression at Month 9 who stopped dosing were collected through Day 294 (42 days after last dose). The same event may appear as both an AE and a Serious Adverse Event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. Safety population: All participants who received at least 1 dose of patisiran-LNP or placebo. Participants were analyzed according to the treatment received.	1.3% 1/77 • Number of events 1 • All Adverse Events (AEs) that occurred from start of study drug administration through End of Study (Day 567), or Follow-up (Day 602) if patient did not enter open-label extension study. AEs for patients with Rapid Disease Progression at Month 9 who stopped dosing were collected through Day 294 (42 days after last dose). The same event may appear as both an AE and a Serious Adverse Event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. Safety population: All participants who received at least 1 dose of patisiran-LNP or placebo. Participants were analyzed according to the treatment received.

Other adverse events
Measure	Patisiran (ALN-TTR02) n=148 participants at risk All patients who received at least 1 dose of patisiran (ALN-TTR02)	Placebo n=77 participants at risk All patients who received at least 1 dose of placebo
Gastrointestinal disorders Diarrhoea	33.8% 50/148 • Number of events 156 • All Adverse Events (AEs) that occurred from start of study drug administration through End of Study (Day 567), or Follow-up (Day 602) if patient did not enter open-label extension study. AEs for patients with Rapid Disease Progression at Month 9 who stopped dosing were collected through Day 294 (42 days after last dose). The same event may appear as both an AE and a Serious Adverse Event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. Safety population: All participants who received at least 1 dose of patisiran-LNP or placebo. Participants were analyzed according to the treatment received.	36.4% 28/77 • Number of events 94 • All Adverse Events (AEs) that occurred from start of study drug administration through End of Study (Day 567), or Follow-up (Day 602) if patient did not enter open-label extension study. AEs for patients with Rapid Disease Progression at Month 9 who stopped dosing were collected through Day 294 (42 days after last dose). The same event may appear as both an AE and a Serious Adverse Event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. Safety population: All participants who received at least 1 dose of patisiran-LNP or placebo. Participants were analyzed according to the treatment received.
General disorders Oedema peripheral	29.1% 43/148 • Number of events 68 • All Adverse Events (AEs) that occurred from start of study drug administration through End of Study (Day 567), or Follow-up (Day 602) if patient did not enter open-label extension study. AEs for patients with Rapid Disease Progression at Month 9 who stopped dosing were collected through Day 294 (42 days after last dose). The same event may appear as both an AE and a Serious Adverse Event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. Safety population: All participants who received at least 1 dose of patisiran-LNP or placebo. Participants were analyzed according to the treatment received.	22.1% 17/77 • Number of events 35 • All Adverse Events (AEs) that occurred from start of study drug administration through End of Study (Day 567), or Follow-up (Day 602) if patient did not enter open-label extension study. AEs for patients with Rapid Disease Progression at Month 9 who stopped dosing were collected through Day 294 (42 days after last dose). The same event may appear as both an AE and a Serious Adverse Event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. Safety population: All participants who received at least 1 dose of patisiran-LNP or placebo. Participants were analyzed according to the treatment received.
Immune system disorders Infusion related reaction	18.9% 28/148 • Number of events 145 • All Adverse Events (AEs) that occurred from start of study drug administration through End of Study (Day 567), or Follow-up (Day 602) if patient did not enter open-label extension study. AEs for patients with Rapid Disease Progression at Month 9 who stopped dosing were collected through Day 294 (42 days after last dose). The same event may appear as both an AE and a Serious Adverse Event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. Safety population: All participants who received at least 1 dose of patisiran-LNP or placebo. Participants were analyzed according to the treatment received.	9.1% 7/77 • Number of events 79 • All Adverse Events (AEs) that occurred from start of study drug administration through End of Study (Day 567), or Follow-up (Day 602) if patient did not enter open-label extension study. AEs for patients with Rapid Disease Progression at Month 9 who stopped dosing were collected through Day 294 (42 days after last dose). The same event may appear as both an AE and a Serious Adverse Event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. Safety population: All participants who received at least 1 dose of patisiran-LNP or placebo. Participants were analyzed according to the treatment received.
Injury, poisoning and procedural complications Fall	16.9% 25/148 • Number of events 47 • All Adverse Events (AEs) that occurred from start of study drug administration through End of Study (Day 567), or Follow-up (Day 602) if patient did not enter open-label extension study. AEs for patients with Rapid Disease Progression at Month 9 who stopped dosing were collected through Day 294 (42 days after last dose). The same event may appear as both an AE and a Serious Adverse Event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. Safety population: All participants who received at least 1 dose of patisiran-LNP or placebo. Participants were analyzed according to the treatment received.	28.6% 22/77 • Number of events 42 • All Adverse Events (AEs) that occurred from start of study drug administration through End of Study (Day 567), or Follow-up (Day 602) if patient did not enter open-label extension study. AEs for patients with Rapid Disease Progression at Month 9 who stopped dosing were collected through Day 294 (42 days after last dose). The same event may appear as both an AE and a Serious Adverse Event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. Safety population: All participants who received at least 1 dose of patisiran-LNP or placebo. Participants were analyzed according to the treatment received.
Gastrointestinal disorders Constipation	14.9% 22/148 • Number of events 29 • All Adverse Events (AEs) that occurred from start of study drug administration through End of Study (Day 567), or Follow-up (Day 602) if patient did not enter open-label extension study. AEs for patients with Rapid Disease Progression at Month 9 who stopped dosing were collected through Day 294 (42 days after last dose). The same event may appear as both an AE and a Serious Adverse Event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. Safety population: All participants who received at least 1 dose of patisiran-LNP or placebo. Participants were analyzed according to the treatment received.	15.6% 12/77 • Number of events 17 • All Adverse Events (AEs) that occurred from start of study drug administration through End of Study (Day 567), or Follow-up (Day 602) if patient did not enter open-label extension study. AEs for patients with Rapid Disease Progression at Month 9 who stopped dosing were collected through Day 294 (42 days after last dose). The same event may appear as both an AE and a Serious Adverse Event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. Safety population: All participants who received at least 1 dose of patisiran-LNP or placebo. Participants were analyzed according to the treatment received.
Gastrointestinal disorders Nausea	14.9% 22/148 • Number of events 50 • All Adverse Events (AEs) that occurred from start of study drug administration through End of Study (Day 567), or Follow-up (Day 602) if patient did not enter open-label extension study. AEs for patients with Rapid Disease Progression at Month 9 who stopped dosing were collected through Day 294 (42 days after last dose). The same event may appear as both an AE and a Serious Adverse Event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. Safety population: All participants who received at least 1 dose of patisiran-LNP or placebo. Participants were analyzed according to the treatment received.	20.8% 16/77 • Number of events 22 • All Adverse Events (AEs) that occurred from start of study drug administration through End of Study (Day 567), or Follow-up (Day 602) if patient did not enter open-label extension study. AEs for patients with Rapid Disease Progression at Month 9 who stopped dosing were collected through Day 294 (42 days after last dose). The same event may appear as both an AE and a Serious Adverse Event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. Safety population: All participants who received at least 1 dose of patisiran-LNP or placebo. Participants were analyzed according to the treatment received.
Nervous system disorders Dizziness	12.8% 19/148 • Number of events 24 • All Adverse Events (AEs) that occurred from start of study drug administration through End of Study (Day 567), or Follow-up (Day 602) if patient did not enter open-label extension study. AEs for patients with Rapid Disease Progression at Month 9 who stopped dosing were collected through Day 294 (42 days after last dose). The same event may appear as both an AE and a Serious Adverse Event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. Safety population: All participants who received at least 1 dose of patisiran-LNP or placebo. Participants were analyzed according to the treatment received.	14.3% 11/77 • Number of events 37 • All Adverse Events (AEs) that occurred from start of study drug administration through End of Study (Day 567), or Follow-up (Day 602) if patient did not enter open-label extension study. AEs for patients with Rapid Disease Progression at Month 9 who stopped dosing were collected through Day 294 (42 days after last dose). The same event may appear as both an AE and a Serious Adverse Event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. Safety population: All participants who received at least 1 dose of patisiran-LNP or placebo. Participants were analyzed according to the treatment received.
Infections and infestations Urinary tract infection	12.8% 19/148 • Number of events 40 • All Adverse Events (AEs) that occurred from start of study drug administration through End of Study (Day 567), or Follow-up (Day 602) if patient did not enter open-label extension study. AEs for patients with Rapid Disease Progression at Month 9 who stopped dosing were collected through Day 294 (42 days after last dose). The same event may appear as both an AE and a Serious Adverse Event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. Safety population: All participants who received at least 1 dose of patisiran-LNP or placebo. Participants were analyzed according to the treatment received.	15.6% 12/77 • Number of events 18 • All Adverse Events (AEs) that occurred from start of study drug administration through End of Study (Day 567), or Follow-up (Day 602) if patient did not enter open-label extension study. AEs for patients with Rapid Disease Progression at Month 9 who stopped dosing were collected through Day 294 (42 days after last dose). The same event may appear as both an AE and a Serious Adverse Event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. Safety population: All participants who received at least 1 dose of patisiran-LNP or placebo. Participants were analyzed according to the treatment received.
General disorders Fatigue	12.2% 18/148 • Number of events 27 • All Adverse Events (AEs) that occurred from start of study drug administration through End of Study (Day 567), or Follow-up (Day 602) if patient did not enter open-label extension study. AEs for patients with Rapid Disease Progression at Month 9 who stopped dosing were collected through Day 294 (42 days after last dose). The same event may appear as both an AE and a Serious Adverse Event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. Safety population: All participants who received at least 1 dose of patisiran-LNP or placebo. Participants were analyzed according to the treatment received.	10.4% 8/77 • Number of events 18 • All Adverse Events (AEs) that occurred from start of study drug administration through End of Study (Day 567), or Follow-up (Day 602) if patient did not enter open-label extension study. AEs for patients with Rapid Disease Progression at Month 9 who stopped dosing were collected through Day 294 (42 days after last dose). The same event may appear as both an AE and a Serious Adverse Event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. Safety population: All participants who received at least 1 dose of patisiran-LNP or placebo. Participants were analyzed according to the treatment received.
Nervous system disorders Headache	10.8% 16/148 • Number of events 25 • All Adverse Events (AEs) that occurred from start of study drug administration through End of Study (Day 567), or Follow-up (Day 602) if patient did not enter open-label extension study. AEs for patients with Rapid Disease Progression at Month 9 who stopped dosing were collected through Day 294 (42 days after last dose). The same event may appear as both an AE and a Serious Adverse Event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. Safety population: All participants who received at least 1 dose of patisiran-LNP or placebo. Participants were analyzed according to the treatment received.	11.7% 9/77 • Number of events 10 • All Adverse Events (AEs) that occurred from start of study drug administration through End of Study (Day 567), or Follow-up (Day 602) if patient did not enter open-label extension study. AEs for patients with Rapid Disease Progression at Month 9 who stopped dosing were collected through Day 294 (42 days after last dose). The same event may appear as both an AE and a Serious Adverse Event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. Safety population: All participants who received at least 1 dose of patisiran-LNP or placebo. Participants were analyzed according to the treatment received.
Respiratory, thoracic and mediastinal disorders Cough	10.1% 15/148 • Number of events 18 • All Adverse Events (AEs) that occurred from start of study drug administration through End of Study (Day 567), or Follow-up (Day 602) if patient did not enter open-label extension study. AEs for patients with Rapid Disease Progression at Month 9 who stopped dosing were collected through Day 294 (42 days after last dose). The same event may appear as both an AE and a Serious Adverse Event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. Safety population: All participants who received at least 1 dose of patisiran-LNP or placebo. Participants were analyzed according to the treatment received.	11.7% 9/77 • Number of events 11 • All Adverse Events (AEs) that occurred from start of study drug administration through End of Study (Day 567), or Follow-up (Day 602) if patient did not enter open-label extension study. AEs for patients with Rapid Disease Progression at Month 9 who stopped dosing were collected through Day 294 (42 days after last dose). The same event may appear as both an AE and a Serious Adverse Event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. Safety population: All participants who received at least 1 dose of patisiran-LNP or placebo. Participants were analyzed according to the treatment received.
Psychiatric disorders Insomnia	10.1% 15/148 • Number of events 24 • All Adverse Events (AEs) that occurred from start of study drug administration through End of Study (Day 567), or Follow-up (Day 602) if patient did not enter open-label extension study. AEs for patients with Rapid Disease Progression at Month 9 who stopped dosing were collected through Day 294 (42 days after last dose). The same event may appear as both an AE and a Serious Adverse Event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. Safety population: All participants who received at least 1 dose of patisiran-LNP or placebo. Participants were analyzed according to the treatment received.	9.1% 7/77 • Number of events 12 • All Adverse Events (AEs) that occurred from start of study drug administration through End of Study (Day 567), or Follow-up (Day 602) if patient did not enter open-label extension study. AEs for patients with Rapid Disease Progression at Month 9 who stopped dosing were collected through Day 294 (42 days after last dose). The same event may appear as both an AE and a Serious Adverse Event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. Safety population: All participants who received at least 1 dose of patisiran-LNP or placebo. Participants were analyzed according to the treatment received.
Infections and infestations Nasopharyngitis	10.1% 15/148 • Number of events 26 • All Adverse Events (AEs) that occurred from start of study drug administration through End of Study (Day 567), or Follow-up (Day 602) if patient did not enter open-label extension study. AEs for patients with Rapid Disease Progression at Month 9 who stopped dosing were collected through Day 294 (42 days after last dose). The same event may appear as both an AE and a Serious Adverse Event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. Safety population: All participants who received at least 1 dose of patisiran-LNP or placebo. Participants were analyzed according to the treatment received.	7.8% 6/77 • Number of events 11 • All Adverse Events (AEs) that occurred from start of study drug administration through End of Study (Day 567), or Follow-up (Day 602) if patient did not enter open-label extension study. AEs for patients with Rapid Disease Progression at Month 9 who stopped dosing were collected through Day 294 (42 days after last dose). The same event may appear as both an AE and a Serious Adverse Event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. Safety population: All participants who received at least 1 dose of patisiran-LNP or placebo. Participants were analyzed according to the treatment received.
General disorders Asthenia	9.5% 14/148 • Number of events 25 • All Adverse Events (AEs) that occurred from start of study drug administration through End of Study (Day 567), or Follow-up (Day 602) if patient did not enter open-label extension study. AEs for patients with Rapid Disease Progression at Month 9 who stopped dosing were collected through Day 294 (42 days after last dose). The same event may appear as both an AE and a Serious Adverse Event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. Safety population: All participants who received at least 1 dose of patisiran-LNP or placebo. Participants were analyzed according to the treatment received.	10.4% 8/77 • Number of events 11 • All Adverse Events (AEs) that occurred from start of study drug administration through End of Study (Day 567), or Follow-up (Day 602) if patient did not enter open-label extension study. AEs for patients with Rapid Disease Progression at Month 9 who stopped dosing were collected through Day 294 (42 days after last dose). The same event may appear as both an AE and a Serious Adverse Event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. Safety population: All participants who received at least 1 dose of patisiran-LNP or placebo. Participants were analyzed according to the treatment received.
Gastrointestinal disorders Vomiting	9.5% 14/148 • Number of events 20 • All Adverse Events (AEs) that occurred from start of study drug administration through End of Study (Day 567), or Follow-up (Day 602) if patient did not enter open-label extension study. AEs for patients with Rapid Disease Progression at Month 9 who stopped dosing were collected through Day 294 (42 days after last dose). The same event may appear as both an AE and a Serious Adverse Event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. Safety population: All participants who received at least 1 dose of patisiran-LNP or placebo. Participants were analyzed according to the treatment received.	7.8% 6/77 • Number of events 27 • All Adverse Events (AEs) that occurred from start of study drug administration through End of Study (Day 567), or Follow-up (Day 602) if patient did not enter open-label extension study. AEs for patients with Rapid Disease Progression at Month 9 who stopped dosing were collected through Day 294 (42 days after last dose). The same event may appear as both an AE and a Serious Adverse Event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. Safety population: All participants who received at least 1 dose of patisiran-LNP or placebo. Participants were analyzed according to the treatment received.
Infections and infestations Upper respiratory tract infection	8.8% 13/148 • Number of events 16 • All Adverse Events (AEs) that occurred from start of study drug administration through End of Study (Day 567), or Follow-up (Day 602) if patient did not enter open-label extension study. AEs for patients with Rapid Disease Progression at Month 9 who stopped dosing were collected through Day 294 (42 days after last dose). The same event may appear as both an AE and a Serious Adverse Event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. Safety population: All participants who received at least 1 dose of patisiran-LNP or placebo. Participants were analyzed according to the treatment received.	6.5% 5/77 • Number of events 6 • All Adverse Events (AEs) that occurred from start of study drug administration through End of Study (Day 567), or Follow-up (Day 602) if patient did not enter open-label extension study. AEs for patients with Rapid Disease Progression at Month 9 who stopped dosing were collected through Day 294 (42 days after last dose). The same event may appear as both an AE and a Serious Adverse Event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. Safety population: All participants who received at least 1 dose of patisiran-LNP or placebo. Participants were analyzed according to the treatment received.
Gastrointestinal disorders Dyspepsia	8.1% 12/148 • Number of events 23 • All Adverse Events (AEs) that occurred from start of study drug administration through End of Study (Day 567), or Follow-up (Day 602) if patient did not enter open-label extension study. AEs for patients with Rapid Disease Progression at Month 9 who stopped dosing were collected through Day 294 (42 days after last dose). The same event may appear as both an AE and a Serious Adverse Event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. Safety population: All participants who received at least 1 dose of patisiran-LNP or placebo. Participants were analyzed according to the treatment received.	3.9% 3/77 • Number of events 5 • All Adverse Events (AEs) that occurred from start of study drug administration through End of Study (Day 567), or Follow-up (Day 602) if patient did not enter open-label extension study. AEs for patients with Rapid Disease Progression at Month 9 who stopped dosing were collected through Day 294 (42 days after last dose). The same event may appear as both an AE and a Serious Adverse Event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. Safety population: All participants who received at least 1 dose of patisiran-LNP or placebo. Participants were analyzed according to the treatment received.
Musculoskeletal and connective tissue disorders Muscle spasms	8.1% 12/148 • Number of events 18 • All Adverse Events (AEs) that occurred from start of study drug administration through End of Study (Day 567), or Follow-up (Day 602) if patient did not enter open-label extension study. AEs for patients with Rapid Disease Progression at Month 9 who stopped dosing were collected through Day 294 (42 days after last dose). The same event may appear as both an AE and a Serious Adverse Event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. Safety population: All participants who received at least 1 dose of patisiran-LNP or placebo. Participants were analyzed according to the treatment received.	1.3% 1/77 • Number of events 1 • All Adverse Events (AEs) that occurred from start of study drug administration through End of Study (Day 567), or Follow-up (Day 602) if patient did not enter open-label extension study. AEs for patients with Rapid Disease Progression at Month 9 who stopped dosing were collected through Day 294 (42 days after last dose). The same event may appear as both an AE and a Serious Adverse Event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. Safety population: All participants who received at least 1 dose of patisiran-LNP or placebo. Participants were analyzed according to the treatment received.
Musculoskeletal and connective tissue disorders Arthralgia	7.4% 11/148 • Number of events 13 • All Adverse Events (AEs) that occurred from start of study drug administration through End of Study (Day 567), or Follow-up (Day 602) if patient did not enter open-label extension study. AEs for patients with Rapid Disease Progression at Month 9 who stopped dosing were collected through Day 294 (42 days after last dose). The same event may appear as both an AE and a Serious Adverse Event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. Safety population: All participants who received at least 1 dose of patisiran-LNP or placebo. Participants were analyzed according to the treatment received.	0.00% 0/77 • All Adverse Events (AEs) that occurred from start of study drug administration through End of Study (Day 567), or Follow-up (Day 602) if patient did not enter open-label extension study. AEs for patients with Rapid Disease Progression at Month 9 who stopped dosing were collected through Day 294 (42 days after last dose). The same event may appear as both an AE and a Serious Adverse Event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. Safety population: All participants who received at least 1 dose of patisiran-LNP or placebo. Participants were analyzed according to the treatment received.
Cardiac disorders Atrial fibrillation	7.4% 11/148 • Number of events 12 • All Adverse Events (AEs) that occurred from start of study drug administration through End of Study (Day 567), or Follow-up (Day 602) if patient did not enter open-label extension study. AEs for patients with Rapid Disease Progression at Month 9 who stopped dosing were collected through Day 294 (42 days after last dose). The same event may appear as both an AE and a Serious Adverse Event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. Safety population: All participants who received at least 1 dose of patisiran-LNP or placebo. Participants were analyzed according to the treatment received.	6.5% 5/77 • Number of events 6 • All Adverse Events (AEs) that occurred from start of study drug administration through End of Study (Day 567), or Follow-up (Day 602) if patient did not enter open-label extension study. AEs for patients with Rapid Disease Progression at Month 9 who stopped dosing were collected through Day 294 (42 days after last dose). The same event may appear as both an AE and a Serious Adverse Event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. Safety population: All participants who received at least 1 dose of patisiran-LNP or placebo. Participants were analyzed according to the treatment received.
Infections and infestations Influenza	7.4% 11/148 • Number of events 13 • All Adverse Events (AEs) that occurred from start of study drug administration through End of Study (Day 567), or Follow-up (Day 602) if patient did not enter open-label extension study. AEs for patients with Rapid Disease Progression at Month 9 who stopped dosing were collected through Day 294 (42 days after last dose). The same event may appear as both an AE and a Serious Adverse Event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. Safety population: All participants who received at least 1 dose of patisiran-LNP or placebo. Participants were analyzed according to the treatment received.	5.2% 4/77 • Number of events 4 • All Adverse Events (AEs) that occurred from start of study drug administration through End of Study (Day 567), or Follow-up (Day 602) if patient did not enter open-label extension study. AEs for patients with Rapid Disease Progression at Month 9 who stopped dosing were collected through Day 294 (42 days after last dose). The same event may appear as both an AE and a Serious Adverse Event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. Safety population: All participants who received at least 1 dose of patisiran-LNP or placebo. Participants were analyzed according to the treatment received.
General disorders Pyrexia	7.4% 11/148 • Number of events 12 • All Adverse Events (AEs) that occurred from start of study drug administration through End of Study (Day 567), or Follow-up (Day 602) if patient did not enter open-label extension study. AEs for patients with Rapid Disease Progression at Month 9 who stopped dosing were collected through Day 294 (42 days after last dose). The same event may appear as both an AE and a Serious Adverse Event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. Safety population: All participants who received at least 1 dose of patisiran-LNP or placebo. Participants were analyzed according to the treatment received.	6.5% 5/77 • Number of events 6 • All Adverse Events (AEs) that occurred from start of study drug administration through End of Study (Day 567), or Follow-up (Day 602) if patient did not enter open-label extension study. AEs for patients with Rapid Disease Progression at Month 9 who stopped dosing were collected through Day 294 (42 days after last dose). The same event may appear as both an AE and a Serious Adverse Event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. Safety population: All participants who received at least 1 dose of patisiran-LNP or placebo. Participants were analyzed according to the treatment received.
Musculoskeletal and connective tissue disorders Back pain	6.8% 10/148 • Number of events 11 • All Adverse Events (AEs) that occurred from start of study drug administration through End of Study (Day 567), or Follow-up (Day 602) if patient did not enter open-label extension study. AEs for patients with Rapid Disease Progression at Month 9 who stopped dosing were collected through Day 294 (42 days after last dose). The same event may appear as both an AE and a Serious Adverse Event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. Safety population: All participants who received at least 1 dose of patisiran-LNP or placebo. Participants were analyzed according to the treatment received.	7.8% 6/77 • Number of events 9 • All Adverse Events (AEs) that occurred from start of study drug administration through End of Study (Day 567), or Follow-up (Day 602) if patient did not enter open-label extension study. AEs for patients with Rapid Disease Progression at Month 9 who stopped dosing were collected through Day 294 (42 days after last dose). The same event may appear as both an AE and a Serious Adverse Event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. Safety population: All participants who received at least 1 dose of patisiran-LNP or placebo. Participants were analyzed according to the treatment received.
Skin and subcutaneous tissue disorders Erythema	6.8% 10/148 • Number of events 51 • All Adverse Events (AEs) that occurred from start of study drug administration through End of Study (Day 567), or Follow-up (Day 602) if patient did not enter open-label extension study. AEs for patients with Rapid Disease Progression at Month 9 who stopped dosing were collected through Day 294 (42 days after last dose). The same event may appear as both an AE and a Serious Adverse Event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. Safety population: All participants who received at least 1 dose of patisiran-LNP or placebo. Participants were analyzed according to the treatment received.	2.6% 2/77 • Number of events 2 • All Adverse Events (AEs) that occurred from start of study drug administration through End of Study (Day 567), or Follow-up (Day 602) if patient did not enter open-label extension study. AEs for patients with Rapid Disease Progression at Month 9 who stopped dosing were collected through Day 294 (42 days after last dose). The same event may appear as both an AE and a Serious Adverse Event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. Safety population: All participants who received at least 1 dose of patisiran-LNP or placebo. Participants were analyzed according to the treatment received.
Nervous system disorders Neuralgia	6.8% 10/148 • Number of events 29 • All Adverse Events (AEs) that occurred from start of study drug administration through End of Study (Day 567), or Follow-up (Day 602) if patient did not enter open-label extension study. AEs for patients with Rapid Disease Progression at Month 9 who stopped dosing were collected through Day 294 (42 days after last dose). The same event may appear as both an AE and a Serious Adverse Event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. Safety population: All participants who received at least 1 dose of patisiran-LNP or placebo. Participants were analyzed according to the treatment received.	6.5% 5/77 • Number of events 13 • All Adverse Events (AEs) that occurred from start of study drug administration through End of Study (Day 567), or Follow-up (Day 602) if patient did not enter open-label extension study. AEs for patients with Rapid Disease Progression at Month 9 who stopped dosing were collected through Day 294 (42 days after last dose). The same event may appear as both an AE and a Serious Adverse Event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. Safety population: All participants who received at least 1 dose of patisiran-LNP or placebo. Participants were analyzed according to the treatment received.
Musculoskeletal and connective tissue disorders Pain in extremity	6.8% 10/148 • Number of events 13 • All Adverse Events (AEs) that occurred from start of study drug administration through End of Study (Day 567), or Follow-up (Day 602) if patient did not enter open-label extension study. AEs for patients with Rapid Disease Progression at Month 9 who stopped dosing were collected through Day 294 (42 days after last dose). The same event may appear as both an AE and a Serious Adverse Event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. Safety population: All participants who received at least 1 dose of patisiran-LNP or placebo. Participants were analyzed according to the treatment received.	10.4% 8/77 • Number of events 12 • All Adverse Events (AEs) that occurred from start of study drug administration through End of Study (Day 567), or Follow-up (Day 602) if patient did not enter open-label extension study. AEs for patients with Rapid Disease Progression at Month 9 who stopped dosing were collected through Day 294 (42 days after last dose). The same event may appear as both an AE and a Serious Adverse Event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. Safety population: All participants who received at least 1 dose of patisiran-LNP or placebo. Participants were analyzed according to the treatment received.
Infections and infestations Bronchitis	6.1% 9/148 • Number of events 11 • All Adverse Events (AEs) that occurred from start of study drug administration through End of Study (Day 567), or Follow-up (Day 602) if patient did not enter open-label extension study. AEs for patients with Rapid Disease Progression at Month 9 who stopped dosing were collected through Day 294 (42 days after last dose). The same event may appear as both an AE and a Serious Adverse Event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. Safety population: All participants who received at least 1 dose of patisiran-LNP or placebo. Participants were analyzed according to the treatment received.	2.6% 2/77 • Number of events 2 • All Adverse Events (AEs) that occurred from start of study drug administration through End of Study (Day 567), or Follow-up (Day 602) if patient did not enter open-label extension study. AEs for patients with Rapid Disease Progression at Month 9 who stopped dosing were collected through Day 294 (42 days after last dose). The same event may appear as both an AE and a Serious Adverse Event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. Safety population: All participants who received at least 1 dose of patisiran-LNP or placebo. Participants were analyzed according to the treatment received.
Respiratory, thoracic and mediastinal disorders Dyspnoea	6.1% 9/148 • Number of events 13 • All Adverse Events (AEs) that occurred from start of study drug administration through End of Study (Day 567), or Follow-up (Day 602) if patient did not enter open-label extension study. AEs for patients with Rapid Disease Progression at Month 9 who stopped dosing were collected through Day 294 (42 days after last dose). The same event may appear as both an AE and a Serious Adverse Event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. Safety population: All participants who received at least 1 dose of patisiran-LNP or placebo. Participants were analyzed according to the treatment received.	0.00% 0/77 • All Adverse Events (AEs) that occurred from start of study drug administration through End of Study (Day 567), or Follow-up (Day 602) if patient did not enter open-label extension study. AEs for patients with Rapid Disease Progression at Month 9 who stopped dosing were collected through Day 294 (42 days after last dose). The same event may appear as both an AE and a Serious Adverse Event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. Safety population: All participants who received at least 1 dose of patisiran-LNP or placebo. Participants were analyzed according to the treatment received.
Nervous system disorders Balance disorder	5.4% 8/148 • Number of events 10 • All Adverse Events (AEs) that occurred from start of study drug administration through End of Study (Day 567), or Follow-up (Day 602) if patient did not enter open-label extension study. AEs for patients with Rapid Disease Progression at Month 9 who stopped dosing were collected through Day 294 (42 days after last dose). The same event may appear as both an AE and a Serious Adverse Event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. Safety population: All participants who received at least 1 dose of patisiran-LNP or placebo. Participants were analyzed according to the treatment received.	2.6% 2/77 • Number of events 2 • All Adverse Events (AEs) that occurred from start of study drug administration through End of Study (Day 567), or Follow-up (Day 602) if patient did not enter open-label extension study. AEs for patients with Rapid Disease Progression at Month 9 who stopped dosing were collected through Day 294 (42 days after last dose). The same event may appear as both an AE and a Serious Adverse Event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. Safety population: All participants who received at least 1 dose of patisiran-LNP or placebo. Participants were analyzed according to the treatment received.
Eye disorders Cataract	5.4% 8/148 • Number of events 10 • All Adverse Events (AEs) that occurred from start of study drug administration through End of Study (Day 567), or Follow-up (Day 602) if patient did not enter open-label extension study. AEs for patients with Rapid Disease Progression at Month 9 who stopped dosing were collected through Day 294 (42 days after last dose). The same event may appear as both an AE and a Serious Adverse Event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. Safety population: All participants who received at least 1 dose of patisiran-LNP or placebo. Participants were analyzed according to the treatment received.	6.5% 5/77 • Number of events 5 • All Adverse Events (AEs) that occurred from start of study drug administration through End of Study (Day 567), or Follow-up (Day 602) if patient did not enter open-label extension study. AEs for patients with Rapid Disease Progression at Month 9 who stopped dosing were collected through Day 294 (42 days after last dose). The same event may appear as both an AE and a Serious Adverse Event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. Safety population: All participants who received at least 1 dose of patisiran-LNP or placebo. Participants were analyzed according to the treatment received.
Gastrointestinal disorders Gastrooesophageal reflux disease	5.4% 8/148 • Number of events 8 • All Adverse Events (AEs) that occurred from start of study drug administration through End of Study (Day 567), or Follow-up (Day 602) if patient did not enter open-label extension study. AEs for patients with Rapid Disease Progression at Month 9 who stopped dosing were collected through Day 294 (42 days after last dose). The same event may appear as both an AE and a Serious Adverse Event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. Safety population: All participants who received at least 1 dose of patisiran-LNP or placebo. Participants were analyzed according to the treatment received.	6.5% 5/77 • Number of events 5 • All Adverse Events (AEs) that occurred from start of study drug administration through End of Study (Day 567), or Follow-up (Day 602) if patient did not enter open-label extension study. AEs for patients with Rapid Disease Progression at Month 9 who stopped dosing were collected through Day 294 (42 days after last dose). The same event may appear as both an AE and a Serious Adverse Event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. Safety population: All participants who received at least 1 dose of patisiran-LNP or placebo. Participants were analyzed according to the treatment received.
Vascular disorders Hypotension	5.4% 8/148 • Number of events 8 • All Adverse Events (AEs) that occurred from start of study drug administration through End of Study (Day 567), or Follow-up (Day 602) if patient did not enter open-label extension study. AEs for patients with Rapid Disease Progression at Month 9 who stopped dosing were collected through Day 294 (42 days after last dose). The same event may appear as both an AE and a Serious Adverse Event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. Safety population: All participants who received at least 1 dose of patisiran-LNP or placebo. Participants were analyzed according to the treatment received.	6.5% 5/77 • Number of events 9 • All Adverse Events (AEs) that occurred from start of study drug administration through End of Study (Day 567), or Follow-up (Day 602) if patient did not enter open-label extension study. AEs for patients with Rapid Disease Progression at Month 9 who stopped dosing were collected through Day 294 (42 days after last dose). The same event may appear as both an AE and a Serious Adverse Event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. Safety population: All participants who received at least 1 dose of patisiran-LNP or placebo. Participants were analyzed according to the treatment received.
Nervous system disorders Paraesthesia	5.4% 8/148 • Number of events 23 • All Adverse Events (AEs) that occurred from start of study drug administration through End of Study (Day 567), or Follow-up (Day 602) if patient did not enter open-label extension study. AEs for patients with Rapid Disease Progression at Month 9 who stopped dosing were collected through Day 294 (42 days after last dose). The same event may appear as both an AE and a Serious Adverse Event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. Safety population: All participants who received at least 1 dose of patisiran-LNP or placebo. Participants were analyzed according to the treatment received.	3.9% 3/77 • Number of events 5 • All Adverse Events (AEs) that occurred from start of study drug administration through End of Study (Day 567), or Follow-up (Day 602) if patient did not enter open-label extension study. AEs for patients with Rapid Disease Progression at Month 9 who stopped dosing were collected through Day 294 (42 days after last dose). The same event may appear as both an AE and a Serious Adverse Event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. Safety population: All participants who received at least 1 dose of patisiran-LNP or placebo. Participants were analyzed according to the treatment received.
Ear and labyrinth disorders Vertigo	5.4% 8/148 • Number of events 11 • All Adverse Events (AEs) that occurred from start of study drug administration through End of Study (Day 567), or Follow-up (Day 602) if patient did not enter open-label extension study. AEs for patients with Rapid Disease Progression at Month 9 who stopped dosing were collected through Day 294 (42 days after last dose). The same event may appear as both an AE and a Serious Adverse Event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. Safety population: All participants who received at least 1 dose of patisiran-LNP or placebo. Participants were analyzed according to the treatment received.	1.3% 1/77 • Number of events 1 • All Adverse Events (AEs) that occurred from start of study drug administration through End of Study (Day 567), or Follow-up (Day 602) if patient did not enter open-label extension study. AEs for patients with Rapid Disease Progression at Month 9 who stopped dosing were collected through Day 294 (42 days after last dose). The same event may appear as both an AE and a Serious Adverse Event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. Safety population: All participants who received at least 1 dose of patisiran-LNP or placebo. Participants were analyzed according to the treatment received.
Vascular disorders Orthostatic hypotension	4.7% 7/148 • Number of events 7 • All Adverse Events (AEs) that occurred from start of study drug administration through End of Study (Day 567), or Follow-up (Day 602) if patient did not enter open-label extension study. AEs for patients with Rapid Disease Progression at Month 9 who stopped dosing were collected through Day 294 (42 days after last dose). The same event may appear as both an AE and a Serious Adverse Event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. Safety population: All participants who received at least 1 dose of patisiran-LNP or placebo. Participants were analyzed according to the treatment received.	7.8% 6/77 • Number of events 7 • All Adverse Events (AEs) that occurred from start of study drug administration through End of Study (Day 567), or Follow-up (Day 602) if patient did not enter open-label extension study. AEs for patients with Rapid Disease Progression at Month 9 who stopped dosing were collected through Day 294 (42 days after last dose). The same event may appear as both an AE and a Serious Adverse Event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. Safety population: All participants who received at least 1 dose of patisiran-LNP or placebo. Participants were analyzed according to the treatment received.
Musculoskeletal and connective tissue disorders Osteoporosis	4.7% 7/148 • Number of events 7 • All Adverse Events (AEs) that occurred from start of study drug administration through End of Study (Day 567), or Follow-up (Day 602) if patient did not enter open-label extension study. AEs for patients with Rapid Disease Progression at Month 9 who stopped dosing were collected through Day 294 (42 days after last dose). The same event may appear as both an AE and a Serious Adverse Event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. Safety population: All participants who received at least 1 dose of patisiran-LNP or placebo. Participants were analyzed according to the treatment received.	9.1% 7/77 • Number of events 7 • All Adverse Events (AEs) that occurred from start of study drug administration through End of Study (Day 567), or Follow-up (Day 602) if patient did not enter open-label extension study. AEs for patients with Rapid Disease Progression at Month 9 who stopped dosing were collected through Day 294 (42 days after last dose). The same event may appear as both an AE and a Serious Adverse Event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. Safety population: All participants who received at least 1 dose of patisiran-LNP or placebo. Participants were analyzed according to the treatment received.
Metabolism and nutrition disorders Vitamin D deficiency	4.7% 7/148 • Number of events 7 • All Adverse Events (AEs) that occurred from start of study drug administration through End of Study (Day 567), or Follow-up (Day 602) if patient did not enter open-label extension study. AEs for patients with Rapid Disease Progression at Month 9 who stopped dosing were collected through Day 294 (42 days after last dose). The same event may appear as both an AE and a Serious Adverse Event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. Safety population: All participants who received at least 1 dose of patisiran-LNP or placebo. Participants were analyzed according to the treatment received.	5.2% 4/77 • Number of events 4 • All Adverse Events (AEs) that occurred from start of study drug administration through End of Study (Day 567), or Follow-up (Day 602) if patient did not enter open-label extension study. AEs for patients with Rapid Disease Progression at Month 9 who stopped dosing were collected through Day 294 (42 days after last dose). The same event may appear as both an AE and a Serious Adverse Event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. Safety population: All participants who received at least 1 dose of patisiran-LNP or placebo. Participants were analyzed according to the treatment received.
Metabolism and nutrition disorders Decreased appetite	4.1% 6/148 • Number of events 6 • All Adverse Events (AEs) that occurred from start of study drug administration through End of Study (Day 567), or Follow-up (Day 602) if patient did not enter open-label extension study. AEs for patients with Rapid Disease Progression at Month 9 who stopped dosing were collected through Day 294 (42 days after last dose). The same event may appear as both an AE and a Serious Adverse Event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. Safety population: All participants who received at least 1 dose of patisiran-LNP or placebo. Participants were analyzed according to the treatment received.	6.5% 5/77 • Number of events 9 • All Adverse Events (AEs) that occurred from start of study drug administration through End of Study (Day 567), or Follow-up (Day 602) if patient did not enter open-label extension study. AEs for patients with Rapid Disease Progression at Month 9 who stopped dosing were collected through Day 294 (42 days after last dose). The same event may appear as both an AE and a Serious Adverse Event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. Safety population: All participants who received at least 1 dose of patisiran-LNP or placebo. Participants were analyzed according to the treatment received.
Renal and urinary disorders Haematuria	4.1% 6/148 • Number of events 9 • All Adverse Events (AEs) that occurred from start of study drug administration through End of Study (Day 567), or Follow-up (Day 602) if patient did not enter open-label extension study. AEs for patients with Rapid Disease Progression at Month 9 who stopped dosing were collected through Day 294 (42 days after last dose). The same event may appear as both an AE and a Serious Adverse Event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. Safety population: All participants who received at least 1 dose of patisiran-LNP or placebo. Participants were analyzed according to the treatment received.	9.1% 7/77 • Number of events 12 • All Adverse Events (AEs) that occurred from start of study drug administration through End of Study (Day 567), or Follow-up (Day 602) if patient did not enter open-label extension study. AEs for patients with Rapid Disease Progression at Month 9 who stopped dosing were collected through Day 294 (42 days after last dose). The same event may appear as both an AE and a Serious Adverse Event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. Safety population: All participants who received at least 1 dose of patisiran-LNP or placebo. Participants were analyzed according to the treatment received.
Investigations Weight decreased	4.1% 6/148 • Number of events 6 • All Adverse Events (AEs) that occurred from start of study drug administration through End of Study (Day 567), or Follow-up (Day 602) if patient did not enter open-label extension study. AEs for patients with Rapid Disease Progression at Month 9 who stopped dosing were collected through Day 294 (42 days after last dose). The same event may appear as both an AE and a Serious Adverse Event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. Safety population: All participants who received at least 1 dose of patisiran-LNP or placebo. Participants were analyzed according to the treatment received.	9.1% 7/77 • Number of events 7 • All Adverse Events (AEs) that occurred from start of study drug administration through End of Study (Day 567), or Follow-up (Day 602) if patient did not enter open-label extension study. AEs for patients with Rapid Disease Progression at Month 9 who stopped dosing were collected through Day 294 (42 days after last dose). The same event may appear as both an AE and a Serious Adverse Event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. Safety population: All participants who received at least 1 dose of patisiran-LNP or placebo. Participants were analyzed according to the treatment received.