Trial Outcomes & Findings for A Study of Risdiplam (RO7034067) in Adult and Pediatric Participants With Spinal Muscular Atrophy (NCT NCT03032172)

Last Updated: 2025-10-01

Results Overview

An AE was any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product, regardless of causal attribution. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

174 participants

Primary outcome timeframe

Baseline up to 5 years

Results posted on

2025-10-01

Participant Flow

A total of 174 adult and pediatric participants with spinal muscular atrophy (SMA) took part in the study at 24 investigative sites across 9 countries from 03 March 2017 to 07 February 2025.

This study included a 2-year treatment period followed by a 3-year open-label extension (OLE) period. Participants previously enrolled in Study BP29420 (NCT02240355) (Moonfish) and treated with the splicing modifier RO6885247 or previously treated with nusinersen, onasemnogene abeparvovec (AVXS-101), or olesoxime, were enrolled to receive risdiplam. 1 participant previously treated with 'Olesoxime' discontinued per physician's decision before receiving any treatment.

Participant milestones

Participant milestones
Measure	Treatment Phase: RO6885247 Participants previously treated with the splicing modifier, RO6885247 or placebo in study BP29420, received risdiplam, orally (PO), once daily (QD), based on their body weight and age during the 24-month treatment phase.	Treatment Phase: Nusinersen Participants previously treated with nusinersen, received risdiplam, PO, QD, based on their body weight and age during the 24-month treatment phase.	Treatment Phase: Olesoxime Participants previously treated with olesoxime, received risdiplam, PO, QD, based on their body weight and age during the 24-month treatment phase.	Treatment Phase: AVXS-101 Participants previously treated with AVXS-101, received risdiplam, PO, QD, based on their body weight and age during the 24-month treatment phase.	OLE Phase: RO6885247 After the 24-month treatment phase, participants who chose to enter the OLE phase continued receiving risdiplam, PO, QD, based on their body weight and age up to a maximum of 3 years.	OLE Phase: Nusinersen After the 24-month treatment phase, participants who chose to enter the OLE phase continued receiving risdiplam, PO, QD, based on their body weight and age up to a maximum of 3 years.	OLE Phase: Olesoxime After the 24-month treatment phase, participants who chose to enter the OLE phase continued receiving risdiplam, PO, QD, based on their body weight and age up to a maximum of 3 years.	OLE Phase: AVXS-101 After the 24-month treatment phase, participants who chose to enter the OLE phase continued receiving risdiplam, PO, QD, based on their body weight and age up to a maximum of 3 years.
Treatment Period STARTED	13	76	71	14	0	0	0	0
Treatment Period Safety-evaluable (SE) Population	13	76	70	14	0	0	0	0
Treatment Period COMPLETED	11	66	64	13	0	0	0	0
Treatment Period NOT COMPLETED	2	10	7	1	0	0	0	0
Open-label Extension Period STARTED	0	0	0	0	11	66	64	13
Open-label Extension Period COMPLETED	0	0	0	0	10	54	49	7
Open-label Extension Period NOT COMPLETED	0	0	0	0	1	12	15	6

Reasons for withdrawal

Reasons for withdrawal
Measure	Treatment Phase: RO6885247 Participants previously treated with the splicing modifier, RO6885247 or placebo in study BP29420, received risdiplam, orally (PO), once daily (QD), based on their body weight and age during the 24-month treatment phase.	Treatment Phase: Nusinersen Participants previously treated with nusinersen, received risdiplam, PO, QD, based on their body weight and age during the 24-month treatment phase.	Treatment Phase: Olesoxime Participants previously treated with olesoxime, received risdiplam, PO, QD, based on their body weight and age during the 24-month treatment phase.	Treatment Phase: AVXS-101 Participants previously treated with AVXS-101, received risdiplam, PO, QD, based on their body weight and age during the 24-month treatment phase.	OLE Phase: RO6885247 After the 24-month treatment phase, participants who chose to enter the OLE phase continued receiving risdiplam, PO, QD, based on their body weight and age up to a maximum of 3 years.	OLE Phase: Nusinersen After the 24-month treatment phase, participants who chose to enter the OLE phase continued receiving risdiplam, PO, QD, based on their body weight and age up to a maximum of 3 years.	OLE Phase: Olesoxime After the 24-month treatment phase, participants who chose to enter the OLE phase continued receiving risdiplam, PO, QD, based on their body weight and age up to a maximum of 3 years.	OLE Phase: AVXS-101 After the 24-month treatment phase, participants who chose to enter the OLE phase continued receiving risdiplam, PO, QD, based on their body weight and age up to a maximum of 3 years.
Treatment Period Adverse Event	0	1	0	0	0	0	0	0
Treatment Period Lack of Efficacy	0	1	0	0	0	0	0	0
Treatment Period Non-compliance With Study Drug	0	1	0	0	0	0	0	0
Treatment Period Reason Not Specified	0	4	1	0	0	0	0	0
Treatment Period Physician Decision	0	2	1	0	0	0	0	0
Treatment Period Discontinued, but Recorded as Completed Open-label Treatment by the Investigator	0	1	2	1	0	0	0	0
Treatment Period Withdrawal by Subject	2	0	3	0	0	0	0	0
Open-label Extension Period Death	0	0	0	0	0	0	0	2
Open-label Extension Period Reason Not Specified	0	0	0	0	0	5	3	0
Open-label Extension Period Pregnancy	0	0	0	0	0	0	1	0
Open-label Extension Period Withdrawal by Subject	0	0	0	0	1	7	11	4

Baseline Characteristics

A Study of Risdiplam (RO7034067) in Adult and Pediatric Participants With Spinal Muscular Atrophy

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	RO6885247 n=13 Participants Participants previously treated with the splicing modifier, RO6885247 or placebo in study BP29420, received risdiplam, PO, QD, based on their body weight and age during the 24-month treatment phase. After the 24-month treatment phase, participants who chose to enter the OLE phase continued receiving risdiplam, PO, QD, based on their body weight and age up to a maximum of 3 years.	Nusinersen n=76 Participants Participants previously treated with nusinersen, received risdiplam, PO, QD, based on their body weight and age during the 24-month treatment phase. After the 24-month treatment phase, participants who chose to enter the OLE phase continued receiving risdiplam, PO, QD, based on their body weight and age up to a maximum of 3 years.	Olesoxime n=71 Participants Participants previously treated with olesoxime, received risdiplam, PO, QD, based on their body weight and age during the 24-month treatment phase. After the 24-month treatment phase, participants who chose to enter the OLE phase continued receiving risdiplam, PO, QD, based on their body weight and age up to a maximum of 3 years.	AVXS-101 n=14 Participants Participants previously treated with AVXS-101, received risdiplam, PO, QD, based on their body weight and age during the 24-month treatment phase. After the 24-month treatment phase, participants who chose to enter the OLE phase continued receiving risdiplam, PO, QD, based on their body weight and age up to a maximum of 3 years.	Total n=174 Participants Total of all reporting groups
Age, Continuous	32.3 years STANDARD_DEVIATION 14.2 • n=5 Participants	16.1 years STANDARD_DEVIATION 13.5 • n=7 Participants	18.5 years STANDARD_DEVIATION 5.7 • n=5 Participants	2.5 years STANDARD_DEVIATION 1.2 • n=4 Participants	17.2 years STANDARD_DEVIATION 11.9 • n=21 Participants
Sex: Female, Male Female	4 Participants n=5 Participants	36 Participants n=7 Participants	36 Participants n=5 Participants	3 Participants n=4 Participants	79 Participants n=21 Participants
Sex: Female, Male Male	9 Participants n=5 Participants	40 Participants n=7 Participants	35 Participants n=5 Participants	11 Participants n=4 Participants	95 Participants n=21 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	6 Participants n=7 Participants	3 Participants n=5 Participants	3 Participants n=4 Participants	12 Participants n=21 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	13 Participants n=5 Participants	66 Participants n=7 Participants	63 Participants n=5 Participants	11 Participants n=4 Participants	153 Participants n=21 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	4 Participants n=7 Participants	5 Participants n=5 Participants	0 Participants n=4 Participants	9 Participants n=21 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Asian	2 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants	2 Participants n=4 Participants	9 Participants n=21 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	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants	1 Participants n=21 Participants
Race (NIH/OMB) White	11 Participants n=5 Participants	66 Participants n=7 Participants	56 Participants n=5 Participants	10 Participants n=4 Participants	143 Participants n=21 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants	1 Participants n=21 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	8 Participants n=7 Participants	12 Participants n=5 Participants	0 Participants n=4 Participants	20 Participants n=21 Participants

PRIMARY outcome

Timeframe: Baseline up to 5 years

Population: SE population included all participants who received at least one dose of risdiplam, whether prematurely withdrawn from the study or not.

Outcome measures

Outcome measures
Measure	RO6885247 n=13 Participants Participants previously treated with the splicing modifier, RO6885247 or placebo in study BP29420, received risdiplam, PO, QD, based on their body weight and age during the 24-month treatment phase. After the 24-month treatment phase, participants who chose to enter the OLE phase continued receiving risdiplam, PO, QD, based on their body weight and age up to a maximum of 3 years.	Nusinersen n=76 Participants Participants previously treated with nusinersen, received risdiplam, PO, QD, based on their body weight and age during the 24-month treatment phase. After the 24-month treatment phase, participants who chose to enter the OLE phase continued receiving risdiplam, PO, QD, based on their body weight and age up to a maximum of 3 years.	Olesoxime n=70 Participants Participants previously treated with olesoxime, received risdiplam, PO, QD, based on their body weight and age during the 24-month treatment phase. After the 24-month treatment phase, participants who chose to enter the OLE phase continued receiving risdiplam, PO, QD, based on their body weight and age up to a maximum of 3 years.	AVXS-101 n=14 Participants Participants previously treated with AVXS-101, received risdiplam, PO, QD, based on their body weight and age during the 24-month treatment phase. After the 24-month treatment phase, participants who chose to enter the OLE phase continued receiving risdiplam, PO, QD, based on their body weight and age up to a maximum of 3 years.
Number of Participants With Adverse Events (AEs)	12 Participants	76 Participants	70 Participants	14 Participants

PRIMARY outcome

Timeframe: Baseline up to 5 years

Population: SE population included all participants who received at least one dose of risdiplam, whether prematurely withdrawn from the study or not.

Outcome measures

Outcome measures
Measure	RO6885247 n=13 Participants Participants previously treated with the splicing modifier, RO6885247 or placebo in study BP29420, received risdiplam, PO, QD, based on their body weight and age during the 24-month treatment phase. After the 24-month treatment phase, participants who chose to enter the OLE phase continued receiving risdiplam, PO, QD, based on their body weight and age up to a maximum of 3 years.	Nusinersen n=76 Participants Participants previously treated with nusinersen, received risdiplam, PO, QD, based on their body weight and age during the 24-month treatment phase. After the 24-month treatment phase, participants who chose to enter the OLE phase continued receiving risdiplam, PO, QD, based on their body weight and age up to a maximum of 3 years.	Olesoxime n=70 Participants Participants previously treated with olesoxime, received risdiplam, PO, QD, based on their body weight and age during the 24-month treatment phase. After the 24-month treatment phase, participants who chose to enter the OLE phase continued receiving risdiplam, PO, QD, based on their body weight and age up to a maximum of 3 years.	AVXS-101 n=14 Participants Participants previously treated with AVXS-101, received risdiplam, PO, QD, based on their body weight and age during the 24-month treatment phase. After the 24-month treatment phase, participants who chose to enter the OLE phase continued receiving risdiplam, PO, QD, based on their body weight and age up to a maximum of 3 years.
Number of Participants Who Discontinued Treatment Due to AEs	0 Participants	1 Participants	0 Participants	0 Participants

PRIMARY outcome

Timeframe: Baseline, Week 52, 104, 156, 208 and 260

Population: SE population included all participants who received at least one dose of risdiplam, whether prematurely withdrawn from the study or not. Overall number analyzed is the number of participants with data available for analysis. No participants from the AVXS-101 arm were assessed for Tanner staging since all participants in this arm were under 9 years of age.

Tanner staging of sexual development is a scale used to assess physical maturation as children transition through adolescence into adulthood. Scale defines physical development based on the following characteristics: pubic hair, penis, and testes development in boys; and pubic hair and breast development in girls. It consists of 5 stages, Stage I (prepubertal) to Stage V (mature adult). Participants under 9 years at screening began Tanner staging assessments at 1st visit following their 9th birthday. Tanner data are presented in three categories: Normal (expected stage of puberty based on participant's age at post-baseline visit), Delayed (pubertal development is behind expectations for age at post-baseline visit), \& Missing (participant did not attend scheduled visit). Tanner staging assessments were scheduled for participants aged 9-17 years but were also conducted in some older participants, up to age 22. Shift in puberty status from baseline to each week has been represented here.

Outcome measures

Outcome measures
Measure	RO6885247 n=4 Participants Participants previously treated with the splicing modifier, RO6885247 or placebo in study BP29420, received risdiplam, PO, QD, based on their body weight and age during the 24-month treatment phase. After the 24-month treatment phase, participants who chose to enter the OLE phase continued receiving risdiplam, PO, QD, based on their body weight and age up to a maximum of 3 years.	Nusinersen n=10 Participants Participants previously treated with nusinersen, received risdiplam, PO, QD, based on their body weight and age during the 24-month treatment phase. After the 24-month treatment phase, participants who chose to enter the OLE phase continued receiving risdiplam, PO, QD, based on their body weight and age up to a maximum of 3 years.	Olesoxime n=31 Participants Participants previously treated with olesoxime, received risdiplam, PO, QD, based on their body weight and age during the 24-month treatment phase. After the 24-month treatment phase, participants who chose to enter the OLE phase continued receiving risdiplam, PO, QD, based on their body weight and age up to a maximum of 3 years.	AVXS-101 Participants previously treated with AVXS-101, received risdiplam, PO, QD, based on their body weight and age during the 24-month treatment phase. After the 24-month treatment phase, participants who chose to enter the OLE phase continued receiving risdiplam, PO, QD, based on their body weight and age up to a maximum of 3 years.
Number of Participants With Shift in Puberty Status From Baseline Baseline Status Normal: Week 52 Status Normal	0 Participants	0 Participants	3 Participants	—
Number of Participants With Shift in Puberty Status From Baseline Baseline Status Normal: Week 52 Status Missing	4 Participants	9 Participants	27 Participants	—
Number of Participants With Shift in Puberty Status From Baseline Baseline Status Delayed: Week 52 Status Normal	0 Participants	0 Participants	1 Participants	—
Number of Participants With Shift in Puberty Status From Baseline Baseline Status Missing: Week 52 Status Missing	0 Participants	1 Participants	0 Participants	—
Number of Participants With Shift in Puberty Status From Baseline Baseline Status Normal: Week 104 Status Normal	0 Participants	4 Participants	15 Participants	—
Number of Participants With Shift in Puberty Status From Baseline Baseline Status Normal: Week 104 Status Missing	4 Participants	5 Participants	15 Participants	—
Number of Participants With Shift in Puberty Status From Baseline Baseline Status Delayed: Week 104 Status Missing	0 Participants	0 Participants	1 Participants	—
Number of Participants With Shift in Puberty Status From Baseline Baseline Status Missing: Week 104 Status Missing	0 Participants	1 Participants	0 Participants	—
Number of Participants With Shift in Puberty Status From Baseline Baseline Status Normal: Week 156 Status Normal	0 Participants	0 Participants	4 Participants	—
Number of Participants With Shift in Puberty Status From Baseline Baseline Status Normal: Week 156 Status Missing	4 Participants	9 Participants	26 Participants	—
Number of Participants With Shift in Puberty Status From Baseline Baseline Status Delayed: Week 156 Status Missing	0 Participants	0 Participants	1 Participants	—
Number of Participants With Shift in Puberty Status From Baseline Baseline Status Missing: Week 156 Status Missing	0 Participants	1 Participants	0 Participants	—
Number of Participants With Shift in Puberty Status From Baseline Baseline Status Normal: Week 208 Status Normal	0 Participants	0 Participants	1 Participants	—
Number of Participants With Shift in Puberty Status From Baseline Baseline Status Normal: Week 208 Status Missing	4 Participants	9 Participants	29 Participants	—
Number of Participants With Shift in Puberty Status From Baseline Baseline Status Delayed: Week 208 Status Missing	0 Participants	0 Participants	1 Participants	—
Number of Participants With Shift in Puberty Status From Baseline Baseline Status Missing: Week Status 208 Missing	0 Participants	1 Participants	0 Participants	—
Number of Participants With Shift in Puberty Status From Baseline Baseline Status Normal: Week 260 Status Missing	4 Participants	9 Participants	30 Participants	—
Number of Participants With Shift in Puberty Status From Baseline Baseline Status Delayed: Week 260 Status Missing	0 Participants	0 Participants	1 Participants	—
Number of Participants With Shift in Puberty Status From Baseline Baseline Status Missing: Week 260 Status Missing	0 Participants	1 Participants	0 Participants	—

PRIMARY outcome

Timeframe: Baseline up to Week 260

Population: SE population included all participants who received at least one dose of risdiplam, whether prematurely withdrawn from the study or not.

Neurological examination was performed by asking questions to the participants and/or their caregiver, as well as observing the participants' behavior in general and while performing certain tasks. Questions and tasks were adapted to the age and motor ability of the participant. For very young participants, observing reaction to a sound, speech development, shifting attention to a newly introduced toy, observing the participant interact with the parent/caregiver \& for older participants examination of social interaction (school, friends, activities, job as appropriate), memory (e.g., with short word recall), reasoning \& language, drawing, etc. Participants with neurological conditions besides those expected with SMA and those expected with SMA are reported.

Outcome measures

Outcome measures
Measure	RO6885247 n=13 Participants Participants previously treated with the splicing modifier, RO6885247 or placebo in study BP29420, received risdiplam, PO, QD, based on their body weight and age during the 24-month treatment phase. After the 24-month treatment phase, participants who chose to enter the OLE phase continued receiving risdiplam, PO, QD, based on their body weight and age up to a maximum of 3 years.	Nusinersen n=76 Participants Participants previously treated with nusinersen, received risdiplam, PO, QD, based on their body weight and age during the 24-month treatment phase. After the 24-month treatment phase, participants who chose to enter the OLE phase continued receiving risdiplam, PO, QD, based on their body weight and age up to a maximum of 3 years.	Olesoxime n=70 Participants Participants previously treated with olesoxime, received risdiplam, PO, QD, based on their body weight and age during the 24-month treatment phase. After the 24-month treatment phase, participants who chose to enter the OLE phase continued receiving risdiplam, PO, QD, based on their body weight and age up to a maximum of 3 years.	AVXS-101 n=14 Participants Participants previously treated with AVXS-101, received risdiplam, PO, QD, based on their body weight and age during the 24-month treatment phase. After the 24-month treatment phase, participants who chose to enter the OLE phase continued receiving risdiplam, PO, QD, based on their body weight and age up to a maximum of 3 years.
Number of Participants With Protocol-defined Neurological Conditions (NC) Week 104: NC Besides Those Expected With SMA	0 Participants	1 Participants	0 Participants	1 Participants
Number of Participants With Protocol-defined Neurological Conditions (NC) Baseline: NC Besides Those Expected With SMA	0 Participants	1 Participants	0 Participants	1 Participants
Number of Participants With Protocol-defined Neurological Conditions (NC) Baseline: NC Expected With SMA	13 Participants	75 Participants	70 Participants	13 Participants
Number of Participants With Protocol-defined Neurological Conditions (NC) Week 2: NC Besides Those Expected With SMA	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Protocol-defined Neurological Conditions (NC) Week 2: NC Expected With SMA	0 Participants	3 Participants	0 Participants	1 Participants
Number of Participants With Protocol-defined Neurological Conditions (NC) Week 4: NC Besides Those Expected With SMA	0 Participants	0 Participants	0 Participants	1 Participants
Number of Participants With Protocol-defined Neurological Conditions (NC) Week 4: NC Expected With SMA	0 Participants	3 Participants	0 Participants	1 Participants
Number of Participants With Protocol-defined Neurological Conditions (NC) Week 13: NC Besides Those Expected With SMA	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Protocol-defined Neurological Conditions (NC) Week 13: NC Expected With SMA	0 Participants	2 Participants	0 Participants	1 Participants
Number of Participants With Protocol-defined Neurological Conditions (NC) Week 26: NC Besides Those Expected With SMA	0 Participants	1 Participants	0 Participants	1 Participants
Number of Participants With Protocol-defined Neurological Conditions (NC) Week 26: NC Expected With SMA	10 Participants	52 Participants	45 Participants	4 Participants
Number of Participants With Protocol-defined Neurological Conditions (NC) Week 39: NC Besides Those Expected With SMA	0 Participants	0 Participants	0 Participants	1 Participants
Number of Participants With Protocol-defined Neurological Conditions (NC) Week 39: NC Expected With SMA	0 Participants	1 Participants	0 Participants	1 Participants
Number of Participants With Protocol-defined Neurological Conditions (NC) Week 52: NC Besides Those Expected With SMA	0 Participants	1 Participants	0 Participants	2 Participants
Number of Participants With Protocol-defined Neurological Conditions (NC) Week 52: NC Expected With SMA	11 Participants	65 Participants	61 Participants	10 Participants
Number of Participants With Protocol-defined Neurological Conditions (NC) Week 61: NC Besides Those Expected With SMA	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Protocol-defined Neurological Conditions (NC) Week 61: NC Expected With SMA	0 Participants	1 Participants	0 Participants	0 Participants
Number of Participants With Protocol-defined Neurological Conditions (NC) Week 65: NC Besides Those Expected With SMA	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Protocol-defined Neurological Conditions (NC) Week 65: NC Expected With SMA	0 Participants	2 Participants	0 Participants	1 Participants
Number of Participants With Protocol-defined Neurological Conditions (NC) Week 78: NC Besides Those Expected With SMA	0 Participants	1 Participants	0 Participants	2 Participants
Number of Participants With Protocol-defined Neurological Conditions (NC) Week 78: NC Expected With SMA	11 Participants	58 Participants	63 Participants	12 Participants
Number of Participants With Protocol-defined Neurological Conditions (NC) Week 87: NC Besides Those Expected With SMA	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Protocol-defined Neurological Conditions (NC) Week 87: NC Expected With SMA	0 Participants	1 Participants	0 Participants	0 Participants
Number of Participants With Protocol-defined Neurological Conditions (NC) Week 91: NC Besides Those Expected With SMA	0 Participants	0 Participants	0 Participants	1 Participants
Number of Participants With Protocol-defined Neurological Conditions (NC) Week 91: NC Expected With SMA	0 Participants	2 Participants	0 Participants	0 Participants
Number of Participants With Protocol-defined Neurological Conditions (NC) Week 104: NC Expected With SMA	11 Participants	64 Participants	63 Participants	12 Participants
Number of Participants With Protocol-defined Neurological Conditions (NC) Week 130: NC Besides Those Expected With SMA	0 Participants	0 Participants	0 Participants	1 Participants
Number of Participants With Protocol-defined Neurological Conditions (NC) Week 130: NC Expected With SMA	10 Participants	63 Participants	60 Participants	12 Participants
Number of Participants With Protocol-defined Neurological Conditions (NC) Week 156: NC Besides Those Expected With SMA	1 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Protocol-defined Neurological Conditions (NC) Week 156: NC Expected With SMA	7 Participants	62 Participants	57 Participants	12 Participants
Number of Participants With Protocol-defined Neurological Conditions (NC) Week 169: NC Besides Those Expected With SMA	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Protocol-defined Neurological Conditions (NC) Week 169: NC Expected With SMA	0 Participants	1 Participants	0 Participants	0 Participants
Number of Participants With Protocol-defined Neurological Conditions (NC) Week 182: NC Besides Those Expected With SMA	0 Participants	3 Participants	0 Participants	0 Participants
Number of Participants With Protocol-defined Neurological Conditions (NC) Week 182: NC Expected With SMA	9 Participants	52 Participants	55 Participants	9 Participants
Number of Participants With Protocol-defined Neurological Conditions (NC) Week 208: NC Besides Those Expected With SMA	0 Participants	2 Participants	1 Participants	0 Participants
Number of Participants With Protocol-defined Neurological Conditions (NC) Week 208: NC Expected With SMA	7 Participants	52 Participants	51 Participants	10 Participants
Number of Participants With Protocol-defined Neurological Conditions (NC) Week 234: NC Besides Those Expected With SMA	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Protocol-defined Neurological Conditions (NC) Week 234: NC Expected With SMA	10 Participants	53 Participants	50 Participants	9 Participants
Number of Participants With Protocol-defined Neurological Conditions (NC) Week 260: NC Besides Those Expected With SMA	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Protocol-defined Neurological Conditions (NC) Week 260: NC Expected With SMA	10 Participants	52 Participants	49 Participants	7 Participants

PRIMARY outcome

Timeframe: Up to approximately 5 years

Population: SE population included all participants who received at least one dose of risdiplam, whether prematurely withdrawn from the study or not. Participants with SI, suicidal behavior, and self-injurious behavior without suicidal intent are reported for this outcome measure. Overall number analyzed are the number of participants with at least one post-baseline assessment.

C-SSRS was used to assess the lifetime suicidality of a participant (baseline) as well as any new instances of suicidality (since last visit). The interview prompts recollection of suicidal ideation (SI), including the intensity of the ideation, behavior and attempts with actual/potential lethality. A modified and reduced version (pediatric version) was used for children (aged 6-11 years). Categories have binary responses (yes/no) \& include: Wish to be Dead; Non-specific Active Suicidal Thoughts; Active SI with Any Methods (Not Plan) without Intent to Act; Active SI with Some Intent to Act, without Specific Plan; Active SI with Specific Plan \& Intent, Preparatory Acts \& Behavior; Aborted Attempt; Interrupted Attempt; Actual Attempt (non-fatal); Completed Suicide. SI or behavior is indicated by a "yes" answer to any of the listed categories. A score of 0 is assigned if no suicide risk is present. A score of 1 or higher indicates SI or behavior.

Outcome measures

Outcome measures
Measure	RO6885247 n=12 Participants Participants previously treated with the splicing modifier, RO6885247 or placebo in study BP29420, received risdiplam, PO, QD, based on their body weight and age during the 24-month treatment phase. After the 24-month treatment phase, participants who chose to enter the OLE phase continued receiving risdiplam, PO, QD, based on their body weight and age up to a maximum of 3 years.	Nusinersen n=68 Participants Participants previously treated with nusinersen, received risdiplam, PO, QD, based on their body weight and age during the 24-month treatment phase. After the 24-month treatment phase, participants who chose to enter the OLE phase continued receiving risdiplam, PO, QD, based on their body weight and age up to a maximum of 3 years.	Olesoxime n=68 Participants Participants previously treated with olesoxime, received risdiplam, PO, QD, based on their body weight and age during the 24-month treatment phase. After the 24-month treatment phase, participants who chose to enter the OLE phase continued receiving risdiplam, PO, QD, based on their body weight and age up to a maximum of 3 years.	AVXS-101 n=10 Participants Participants previously treated with AVXS-101, received risdiplam, PO, QD, based on their body weight and age during the 24-month treatment phase. After the 24-month treatment phase, participants who chose to enter the OLE phase continued receiving risdiplam, PO, QD, based on their body weight and age up to a maximum of 3 years.
Number of Participants With Emergence or Worsening of Symptoms as Assessed Using Columbia Suicide Severity Rating Scale (C-SSRS) Suicidal Ideation	1 Participants	5 Participants	2 Participants	0 Participants
Number of Participants With Emergence or Worsening of Symptoms as Assessed Using Columbia Suicide Severity Rating Scale (C-SSRS) Suicidal Behaviour	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Emergence or Worsening of Symptoms as Assessed Using Columbia Suicide Severity Rating Scale (C-SSRS) Self-injurious Behavior Without Suicidal Intent	0 Participants	0 Participants	1 Participants	0 Participants

PRIMARY outcome

Timeframe: Baseline up to Week 260

Population: SE population included all participants who received at least one dose of risdiplam, whether prematurely withdrawn from the study or not. Overall number analyzed is the number of participants with data available for analysis. Number analyzed is the number of participants with data available for analysis at the specified timepoint.

Weight was measured at baseline, Weeks 65, 91, and every 13 weeks thereafter for participants 2-17 years and at every visit for participants \<2 years. Per protocol, height was not measured at Day 7, Weeks 8, 17, 35, and thus not collected for all participants. No participants in the RO6885247 arm attended the Weeks 65, 169, 195, and 247 visit; none in the AVXS-101 arm attended the Week 247 visit. Symptom-directed height/weight assessments were done at clinically indicated visits as needed.

Outcome measures

Outcome measures
Measure	RO6885247 n=13 Participants Participants previously treated with the splicing modifier, RO6885247 or placebo in study BP29420, received risdiplam, PO, QD, based on their body weight and age during the 24-month treatment phase. After the 24-month treatment phase, participants who chose to enter the OLE phase continued receiving risdiplam, PO, QD, based on their body weight and age up to a maximum of 3 years.	Nusinersen n=76 Participants Participants previously treated with nusinersen, received risdiplam, PO, QD, based on their body weight and age during the 24-month treatment phase. After the 24-month treatment phase, participants who chose to enter the OLE phase continued receiving risdiplam, PO, QD, based on their body weight and age up to a maximum of 3 years.	Olesoxime n=70 Participants Participants previously treated with olesoxime, received risdiplam, PO, QD, based on their body weight and age during the 24-month treatment phase. After the 24-month treatment phase, participants who chose to enter the OLE phase continued receiving risdiplam, PO, QD, based on their body weight and age up to a maximum of 3 years.	AVXS-101 n=14 Participants Participants previously treated with AVXS-101, received risdiplam, PO, QD, based on their body weight and age during the 24-month treatment phase. After the 24-month treatment phase, participants who chose to enter the OLE phase continued receiving risdiplam, PO, QD, based on their body weight and age up to a maximum of 3 years.
Anthropometric Examination: Change From Baseline in Weight Week 260	2.81 kilograms (kg) Standard Deviation 3.49	10.03 kilograms (kg) Standard Deviation 8.41	7.41 kilograms (kg) Standard Deviation 9.11	9.54 kilograms (kg) Standard Deviation 6.23
Anthropometric Examination: Change From Baseline in Weight Baseline	59.19 kilograms (kg) Standard Deviation 20.47	39.29 kilograms (kg) Standard Deviation 22.30	46.48 kilograms (kg) Standard Deviation 15.57	12.87 kilograms (kg) Standard Deviation 3.35
Anthropometric Examination: Change From Baseline in Weight Day 7	0.09 kilograms (kg) Standard Deviation 0.20	0.13 kilograms (kg) Standard Deviation 0.31	—	—
Anthropometric Examination: Change From Baseline in Weight Week 2	-2.79 kilograms (kg) Standard Deviation 10.66	0.15 kilograms (kg) Standard Deviation 0.80	0.19 kilograms (kg) Standard Deviation 1.73	0.00 kilograms (kg) Standard Deviation 0.32
Anthropometric Examination: Change From Baseline in Weight Week 4	-0.89 kilograms (kg) Standard Deviation 3.15	0.29 kilograms (kg) Standard Deviation 0.91	0.37 kilograms (kg) Standard Deviation 1.86	0.03 kilograms (kg) Standard Deviation 0.37
Anthropometric Examination: Change From Baseline in Weight Week 8	-0.17 kilograms (kg) Standard Deviation 2.38	0.00 kilograms (kg) Standard Deviation 0.17	—	—
Anthropometric Examination: Change From Baseline in Weight Week 13	0.45 kilograms (kg) Standard Deviation 1.91	0.64 kilograms (kg) Standard Deviation 1.57	0.63 kilograms (kg) Standard Deviation 2.28	0.07 kilograms (kg) Standard Deviation 0.46
Anthropometric Examination: Change From Baseline in Weight Week 17	-0.33 kilograms (kg) Standard Deviation 2.91	2.07 kilograms (kg) Standard Deviation 3.09	—	—
Anthropometric Examination: Change From Baseline in Weight Week 26	-1.26 kilograms (kg) Standard Deviation 3.99	1.25 kilograms (kg) Standard Deviation 2.01	1.14 kilograms (kg) Standard Deviation 4.03	0.52 kilograms (kg) Standard Deviation 0.68
Anthropometric Examination: Change From Baseline in Weight Week 35	-1.51 kilograms (kg) Standard Deviation 4.21	2.12 kilograms (kg) Standard Deviation 1.69	-0.10 kilograms (kg) Standard Deviation 3.36	—
Anthropometric Examination: Change From Baseline in Weight Week 39	-0.20 kilograms (kg) Standard Deviation 2.55	1.06 kilograms (kg) Standard Deviation 2.96	0.99 kilograms (kg) Standard Deviation 2.68	0.90 kilograms (kg) Standard Deviation 1.02
Anthropometric Examination: Change From Baseline in Weight Week 43	-1.09 kilograms (kg) Standard Deviation 4.17	2.95 kilograms (kg) Standard Deviation 3.92	1.56 kilograms (kg) Standard Deviation 5.29	4.75 kilograms (kg) Standard Deviation 3.32
Anthropometric Examination: Change From Baseline in Weight Week 52	-0.26 kilograms (kg) Standard Deviation 3.32	1.93 kilograms (kg) Standard Deviation 3.84	1.35 kilograms (kg) Standard Deviation 3.39	1.71 kilograms (kg) Standard Deviation 2.13
Anthropometric Examination: Change From Baseline in Weight Week 61	6.40 kilograms (kg) Standard Deviation NA The standard deviation (SD) was not estimable for 1 participant.	2.07 kilograms (kg) Standard Deviation 1.70	0.25 kilograms (kg) Standard Deviation 1.46	1.30 kilograms (kg) Standard Deviation NA The SD was not estimable for 1 participant.
Anthropometric Examination: Change From Baseline in Weight Week 65	—	2.96 kilograms (kg) Standard Deviation 3.14	1.96 kilograms (kg) Standard Deviation 3.87	2.54 kilograms (kg) Standard Deviation 2.40
Anthropometric Examination: Change From Baseline in Weight Week 70	-1.72 kilograms (kg) Standard Deviation 4.27	-0.93 kilograms (kg) Standard Deviation 3.97	-1.38 kilograms (kg) Standard Deviation 3.60	1.30 kilograms (kg) Standard Deviation NA The SD was not estimable for 1 participant.
Anthropometric Examination: Change From Baseline in Weight Week 78	-0.19 kilograms (kg) Standard Deviation 3.81	3.42 kilograms (kg) Standard Deviation 3.84	1.77 kilograms (kg) Standard Deviation 4.31	2.61 kilograms (kg) Standard Deviation 2.37
Anthropometric Examination: Change From Baseline in Weight Week 87	2.15 kilograms (kg) Standard Deviation NA The SD was not estimable for 1 participant.	2.80 kilograms (kg) Standard Deviation 4.67	3.91 kilograms (kg) Standard Deviation 4.37	5.30 kilograms (kg) Standard Deviation 5.80
Anthropometric Examination: Change From Baseline in Weight Week 91	-0.85 kilograms (kg) Standard Deviation 3.68	4.33 kilograms (kg) Standard Deviation 4.75	2.11 kilograms (kg) Standard Deviation 4.99	2.07 kilograms (kg) Standard Deviation 0.92
Anthropometric Examination: Change From Baseline in Weight Week 96	9.60 kilograms (kg) Standard Deviation NA The SD was not estimable for 1 participant.	3.52 kilograms (kg) Standard Deviation 3.12	3.19 kilograms (kg) Standard Deviation 4.98	0.70 kilograms (kg) Standard Deviation NA The SD was not estimable for 1 participant.
Anthropometric Examination: Change From Baseline in Weight Week 104	0.45 kilograms (kg) Standard Deviation 4.50	3.96 kilograms (kg) Standard Deviation 5.33	3.21 kilograms (kg) Standard Deviation 5.02	3.08 kilograms (kg) Standard Deviation 3.18
Anthropometric Examination: Change From Baseline in Weight Week 117	-0.10 kilograms (kg) Standard Deviation NA The SD was not estimable for 1 participant.	4.30 kilograms (kg) Standard Deviation 3.10	3.45 kilograms (kg) Standard Deviation 3.24	1.86 kilograms (kg) Standard Deviation 0.84
Anthropometric Examination: Change From Baseline in Weight Week 130	-0.60 kilograms (kg) Standard Deviation 3.56	5.30 kilograms (kg) Standard Deviation 6.07	2.95 kilograms (kg) Standard Deviation 5.51	3.19 kilograms (kg) Standard Deviation 1.49
Anthropometric Examination: Change From Baseline in Weight Week 143	2.90 kilograms (kg) Standard Deviation NA The SD was not estimable for 1 participant.	2.69 kilograms (kg) Standard Deviation 4.04	4.35 kilograms (kg) Standard Deviation 4.90	1.70 kilograms (kg) Standard Deviation NA The SD was not estimable for 1 participant.
Anthropometric Examination: Change From Baseline in Weight Week 156	0.28 kilograms (kg) Standard Deviation 4.66	6.44 kilograms (kg) Standard Deviation 6.39	3.81 kilograms (kg) Standard Deviation 6.45	4.02 kilograms (kg) Standard Deviation 2.10
Anthropometric Examination: Change From Baseline in Weight Week 169	—	3.29 kilograms (kg) Standard Deviation 5.49	8.90 kilograms (kg) Standard Deviation 4.38	2.10 kilograms (kg) Standard Deviation NA The SD was not estimable for 1 participant.
Anthropometric Examination: Change From Baseline in Weight Week 182	1.94 kilograms (kg) Standard Deviation 4.09	7.37 kilograms (kg) Standard Deviation 6.96	4.27 kilograms (kg) Standard Deviation 7.81	4.97 kilograms (kg) Standard Deviation 2.41
Anthropometric Examination: Change From Baseline in Weight Week 195	—	22.00 kilograms (kg) Standard Deviation NA The SD was not estimable for 1 participant.	7.50 kilograms (kg) Standard Deviation NA The SD was not estimable for 1 participant.	5.20 kilograms (kg) Standard Deviation 0.99
Anthropometric Examination: Change From Baseline in Weight Week 208	0.51 kilograms (kg) Standard Deviation 2.68	8.70 kilograms (kg) Standard Deviation 7.71	4.82 kilograms (kg) Standard Deviation 8.37	5.44 kilograms (kg) Standard Deviation 3.33
Anthropometric Examination: Change From Baseline in Weight Week 221	1.35 kilograms (kg) Standard Deviation 0.49	7.70 kilograms (kg) Standard Deviation NA The SD was not estimable for 1 participant.	3.50 kilograms (kg) Standard Deviation NA The SD was not estimable for 1 participant.	3.80 kilograms (kg) Standard Deviation NA The SD was not estimable for 1 participant.
Anthropometric Examination: Change From Baseline in Weight Week 234	1.56 kilograms (kg) Standard Deviation 2.65	9.26 kilograms (kg) Standard Deviation 7.91	6.29 kilograms (kg) Standard Deviation 8.55	7.77 kilograms (kg) Standard Deviation 5.04
Anthropometric Examination: Change From Baseline in Weight Week 247	—	4.73 kilograms (kg) Standard Deviation 4.89	11.10 kilograms (kg) Standard Deviation NA The SD was not estimable for 1 participant.	—

PRIMARY outcome

Timeframe: Baseline up to Week 260

Population: SE population included all participants who received at least one dose of risdiplam, whether prematurely withdrawn from the study or not. Overall number analyzed is the number of participants with data available for analysis. Number analyzed is the number of participants with data available for analysis at the specified timepoint.

Height of all participants able to stand was measured while standing using a stadiometer, with at least 3 independent measurements, which were averaged. Participants unable to stand during the measurement, height was derived from measurement of ulna length. For very young children, height was measured with child in a lying position using an inflexible length board with fixed headboard \& movable footboard. Height was measured: baseline, Weeks 13,39,52,78 \& 104 for participants 2-17 years; Weeks 52 \& 104 for \>17 years \& every visit for participants \<2 years. After Week 104, measurements occurred every 26 weeks. Per protocol, height was not measured at Weeks 2,4,17,26,35,43,61,65,87,91,96,117,143,169,195,221 \&247 \& thus not collected for all participants. No participants \<17 years in RO6885247, Olesoxime, or AVXS-101 arms attended the Week 260 visit \& no participants in RO6885247 arm attended Week 39. Symptom-directed height assessments were done at clinically indicated visits as needed.

Outcome measures

Outcome measures
Measure	RO6885247 n=13 Participants Participants previously treated with the splicing modifier, RO6885247 or placebo in study BP29420, received risdiplam, PO, QD, based on their body weight and age during the 24-month treatment phase. After the 24-month treatment phase, participants who chose to enter the OLE phase continued receiving risdiplam, PO, QD, based on their body weight and age up to a maximum of 3 years.	Nusinersen n=76 Participants Participants previously treated with nusinersen, received risdiplam, PO, QD, based on their body weight and age during the 24-month treatment phase. After the 24-month treatment phase, participants who chose to enter the OLE phase continued receiving risdiplam, PO, QD, based on their body weight and age up to a maximum of 3 years.	Olesoxime n=70 Participants Participants previously treated with olesoxime, received risdiplam, PO, QD, based on their body weight and age during the 24-month treatment phase. After the 24-month treatment phase, participants who chose to enter the OLE phase continued receiving risdiplam, PO, QD, based on their body weight and age up to a maximum of 3 years.	AVXS-101 n=14 Participants Participants previously treated with AVXS-101, received risdiplam, PO, QD, based on their body weight and age during the 24-month treatment phase. After the 24-month treatment phase, participants who chose to enter the OLE phase continued receiving risdiplam, PO, QD, based on their body weight and age up to a maximum of 3 years.
Anthropometric Examination: Change From Baseline in Height Week 182	-2.25 centimeters (cm) Standard Deviation 5.54	15.36 centimeters (cm) Standard Deviation 11.34	4.67 centimeters (cm) Standard Deviation 6.31	21.54 centimeters (cm) Standard Deviation 2.76
Anthropometric Examination: Change From Baseline in Height Week 195	—	—	—	31.74 centimeters (cm) Standard Deviation NA The SD was not estimable for 1 participant.
Anthropometric Examination: Change From Baseline in Height Week 208	-2.28 centimeters (cm) Standard Deviation 5.52	16.13 centimeters (cm) Standard Deviation 11.69	4.91 centimeters (cm) Standard Deviation 8.60	26.17 centimeters (cm) Standard Deviation 6.55
Anthropometric Examination: Change From Baseline in Height Week 221	0.00 centimeters (cm) Standard Deviation NA The SD was not estimable for 1 participant.	—	9.77 centimeters (cm) Standard Deviation NA The SD was not estimable for 1 participant.	—
Anthropometric Examination: Change From Baseline in Height Week 234	-1.04 centimeters (cm) Standard Deviation 5.25	17.18 centimeters (cm) Standard Deviation 13.14	4.95 centimeters (cm) Standard Deviation 7.88	28.21 centimeters (cm) Standard Deviation 5.49
Anthropometric Examination: Change From Baseline in Height Week 247	—	10.18 centimeters (cm) Standard Deviation 14.39	—	—
Anthropometric Examination: Change From Baseline in Height Week 260	—	29.00 centimeters (cm) Standard Deviation 5.66	—	—
Anthropometric Examination: Change From Baseline in Height Baseline	171.36 centimeters (cm) Standard Deviation 8.36	141.21 centimeters (cm) Standard Deviation 26.17	161.71 centimeters (cm) Standard Deviation 13.86	92.37 centimeters (cm) Standard Deviation 11.23
Anthropometric Examination: Change From Baseline in Height Week 2	—	0.00 centimeters (cm) Standard Deviation 0.00	—	0.00 centimeters (cm) Standard Deviation 0.00
Anthropometric Examination: Change From Baseline in Height Week 4	—	1.00 centimeters (cm) Standard Deviation 1.41	—	0.33 centimeters (cm) Standard Deviation 0.58
Anthropometric Examination: Change From Baseline in Height Week 13	-0.20 centimeters (cm) Standard Deviation 1.71	1.08 centimeters (cm) Standard Deviation 4.10	1.23 centimeters (cm) Standard Deviation 5.09	2.78 centimeters (cm) Standard Deviation 2.14
Anthropometric Examination: Change From Baseline in Height Week 17	-0.84 centimeters (cm) Standard Deviation 3.56	-10.99 centimeters (cm) Standard Deviation 28.36	—	—
Anthropometric Examination: Change From Baseline in Height Week 26	—	6.50 centimeters (cm) Standard Deviation 6.36	—	0.00 centimeters (cm) Standard Deviation 1.41
Anthropometric Examination: Change From Baseline in Height Week 35	-0.40 centimeters (cm) Standard Deviation 3.75	2.92 centimeters (cm) Standard Deviation 3.38	0.05 centimeters (cm) Standard Deviation 1.25	—
Anthropometric Examination: Change From Baseline in Height Week 39	—	4.81 centimeters (cm) Standard Deviation 4.13	6.18 centimeters (cm) Standard Deviation 9.33	2.41 centimeters (cm) Standard Deviation 3.25
Anthropometric Examination: Change From Baseline in Height Week 43	—	11.41 centimeters (cm) Standard Deviation 7.59	3.55 centimeters (cm) Standard Deviation 5.01	7.00 centimeters (cm) Standard Deviation NA The SD was not estimable for 1 participant.
Anthropometric Examination: Change From Baseline in Height Week 52	-0.38 centimeters (cm) Standard Deviation 2.98	6.14 centimeters (cm) Standard Deviation 5.31	2.36 centimeters (cm) Standard Deviation 5.66	6.83 centimeters (cm) Standard Deviation 3.01
Anthropometric Examination: Change From Baseline in Height Week 61	0.00 centimeters (cm) Standard Deviation NA The SD was not estimable for 1 participant.	11.41 centimeters (cm) Standard Deviation 9.06	4.61 centimeters (cm) Standard Deviation 6.33	—
Anthropometric Examination: Change From Baseline in Height Week 65	—	9.80 centimeters (cm) Standard Deviation 6.91	0.88 centimeters (cm) Standard Deviation 0.76	8.00 centimeters (cm) Standard Deviation 1.73
Anthropometric Examination: Change From Baseline in Height Week 78	-0.71 centimeters (cm) Standard Deviation 2.16	9.92 centimeters (cm) Standard Deviation 6.32	3.90 centimeters (cm) Standard Deviation 6.80	9.09 centimeters (cm) Standard Deviation 4.04
Anthropometric Examination: Change From Baseline in Height Week 87	—	—	4.77 centimeters (cm) Standard Deviation 3.05	5.78 centimeters (cm) Standard Deviation NA The SD was not estimable for 1 participant.
Anthropometric Examination: Change From Baseline in Height Week 91	—	17.00 centimeters (cm) Standard Deviation 7.07	—	10.00 centimeters (cm) Standard Deviation 4.24
Anthropometric Examination: Change From Baseline in Height Week 96	—	—	6.96 centimeters (cm) Standard Deviation 14.28	—
Anthropometric Examination: Change From Baseline in Height Week 104	-0.87 centimeters (cm) Standard Deviation 1.92	11.33 centimeters (cm) Standard Deviation 7.14	5.14 centimeters (cm) Standard Deviation 7.33	14.54 centimeters (cm) Standard Deviation 3.95
Anthropometric Examination: Change From Baseline in Height Week 117	—	9.20 centimeters (cm) Standard Deviation 6.11	4.86 centimeters (cm) Standard Deviation 3.15	—
Anthropometric Examination: Change From Baseline in Height Week 130	-1.60 centimeters (cm) Standard Deviation 2.13	12.15 centimeters (cm) Standard Deviation 8.73	4.70 centimeters (cm) Standard Deviation 7.80	16.11 centimeters (cm) Standard Deviation 5.48
Anthropometric Examination: Change From Baseline in Height Week 143	0.00 centimeters (cm) Standard Deviation NA The SD was not estimable for 1 participant.	5.91 centimeters (cm) Standard Deviation 6.39	5.00 centimeters (cm) Standard Deviation NA The SD was not estimable for 1 participant.	—
Anthropometric Examination: Change From Baseline in Height Week 156	-0.20 centimeters (cm) Standard Deviation 0.45	12.90 centimeters (cm) Standard Deviation 10.31	4.43 centimeters (cm) Standard Deviation 6.80	22.02 centimeters (cm) Standard Deviation 4.97
Anthropometric Examination: Change From Baseline in Height Week 169	—	13.46 centimeters (cm) Standard Deviation 12.09	0.00 centimeters (cm) Standard Deviation NA The SD was not estimable for 1 participant.	—

PRIMARY outcome

Timeframe: Baseline up to Week 208

Population: SE population included all participants who received at least one dose of risdiplam, whether prematurely withdrawn from the study or not. Overall number analyzed is the number of participants with data available for analysis. Number analyzed is the number of participants with data available for analysis at the specified timepoint.

Head circumference for participants aged \< 5 years was measured to the nearest 0.1 cm using a flexible, non-stretchable tape. Head circumference was measured around the widest part of the head from the most prominent point on the back of the head (occiput) to the most prominent part of the forehead between the eyebrows. The measurement was repeated three times, and the largest measurement was recorded. Head circumference was assessed for participants \< 5 years of age. Since all participants in the RO6885247 and Olesoxime arms were \> 5 years, data were not collected for these arms. Head circumference was not collected at Weeks 35 and 61 (AVXS-101 arm) and Weeks 87, 182, and 208 (Nusinersen arm) because the protocol only required this measurement for participants \< 5 years of age. At these timepoints, neither of the participants \< 5 years attended the visit, and other participants may have been \> 5 years of age.

Outcome measures

Outcome measures
Measure	RO6885247 Participants previously treated with the splicing modifier, RO6885247 or placebo in study BP29420, received risdiplam, PO, QD, based on their body weight and age during the 24-month treatment phase. After the 24-month treatment phase, participants who chose to enter the OLE phase continued receiving risdiplam, PO, QD, based on their body weight and age up to a maximum of 3 years.	Nusinersen n=10 Participants Participants previously treated with nusinersen, received risdiplam, PO, QD, based on their body weight and age during the 24-month treatment phase. After the 24-month treatment phase, participants who chose to enter the OLE phase continued receiving risdiplam, PO, QD, based on their body weight and age up to a maximum of 3 years.	Olesoxime Participants previously treated with olesoxime, received risdiplam, PO, QD, based on their body weight and age during the 24-month treatment phase. After the 24-month treatment phase, participants who chose to enter the OLE phase continued receiving risdiplam, PO, QD, based on their body weight and age up to a maximum of 3 years.	AVXS-101 n=14 Participants Participants previously treated with AVXS-101, received risdiplam, PO, QD, based on their body weight and age during the 24-month treatment phase. After the 24-month treatment phase, participants who chose to enter the OLE phase continued receiving risdiplam, PO, QD, based on their body weight and age up to a maximum of 3 years.
Anthropometric Examination: Change From Baseline in Head Circumference Baseline	—	51.10 cm Standard Deviation 3.43	—	50.61 cm Standard Deviation 2.15
Anthropometric Examination: Change From Baseline in Head Circumference Week 2	—	0.28 cm Standard Deviation 0.85	—	0.26 cm Standard Deviation 0.43
Anthropometric Examination: Change From Baseline in Head Circumference Week 4	—	0.27 cm Standard Deviation 1.55	—	0.17 cm Standard Deviation 0.51
Anthropometric Examination: Change From Baseline in Head Circumference Week 13	—	0.70 cm Standard Deviation 1.54	—	0.51 cm Standard Deviation 0.51
Anthropometric Examination: Change From Baseline in Head Circumference Week 26	—	1.30 cm Standard Deviation 0.77	—	0.58 cm Standard Deviation 1.02
Anthropometric Examination: Change From Baseline in Head Circumference Week 35	—	0.00 cm Standard Deviation NA The SD was not estimable for 1 participant.	—	—
Anthropometric Examination: Change From Baseline in Head Circumference Week 39	—	1.90 cm Standard Deviation 1.15	—	0.42 cm Standard Deviation 0.99
Anthropometric Examination: Change From Baseline in Head Circumference Week 52	—	1.90 cm Standard Deviation 1.15	—	1.34 cm Standard Deviation 0.91
Anthropometric Examination: Change From Baseline in Head Circumference Week 61	—	1.50 cm Standard Deviation NA The SD was not estimable for 1 participant.	—	—
Anthropometric Examination: Change From Baseline in Head Circumference Week 65	—	2.75 cm Standard Deviation 1.77	—	1.67 cm Standard Deviation 1.89
Anthropometric Examination: Change From Baseline in Head Circumference Week 78	—	2.40 cm Standard Deviation 1.44	—	1.58 cm Standard Deviation 0.75
Anthropometric Examination: Change From Baseline in Head Circumference Week 87	—	—	—	0.50 cm Standard Deviation NA The SD was not estimable for 1 participant.
Anthropometric Examination: Change From Baseline in Head Circumference Week 91	—	1.50 cm Standard Deviation NA The SD was not estimable for 1 participant.	—	1.05 cm Standard Deviation 2.05
Anthropometric Examination: Change From Baseline in Head Circumference Week 104	—	1.60 cm Standard Deviation 0.14	—	1.70 cm Standard Deviation 0.77
Anthropometric Examination: Change From Baseline in Head Circumference Week 130	—	5.50 cm Standard Deviation NA The SD was not estimable for 1 participant.	—	2.10 cm Standard Deviation 1.52
Anthropometric Examination: Change From Baseline in Head Circumference Week 156	—	3.00 cm Standard Deviation NA The SD was not estimable for 1 participant.	—	3.00 cm Standard Deviation 0.71
Anthropometric Examination: Change From Baseline in Head Circumference Week 182	—	—	—	3.50 cm Standard Deviation NA The SD was not estimable for 1 participant.
Anthropometric Examination: Change From Baseline in Head Circumference Week 208	—	—	—	3.50 cm Standard Deviation NA The SD was not estimable for 1 participant.

PRIMARY outcome

Timeframe: Predose on Weeks 2, 4, 13, 26, 39, 52, 65, 91 and post-dose on Weeks 1, 4, 13, 52, 91 and 104

Population: PK population included all participants with at least one timepoint with a measurable drug concentration. Overall number analyzed is the number of participants with data available for analysis.

As pre-specified in the protocol, the PK data were not to be compared between participants who received different prior treatments (RO6885247, nusinersen, olesoxime and AVXS-101) received before entering this study, but to analyze the PK parameters of risdiplam. Hence, PK data have been presented in a single arm group irrespective of prior therapies received by the participants in previous studies.

Outcome measures

Outcome measures
Measure	RO6885247 n=173 Participants Participants previously treated with the splicing modifier, RO6885247 or placebo in study BP29420, received risdiplam, PO, QD, based on their body weight and age during the 24-month treatment phase. After the 24-month treatment phase, participants who chose to enter the OLE phase continued receiving risdiplam, PO, QD, based on their body weight and age up to a maximum of 3 years.	Nusinersen Participants previously treated with nusinersen, received risdiplam, PO, QD, based on their body weight and age during the 24-month treatment phase. After the 24-month treatment phase, participants who chose to enter the OLE phase continued receiving risdiplam, PO, QD, based on their body weight and age up to a maximum of 3 years.	Olesoxime Participants previously treated with olesoxime, received risdiplam, PO, QD, based on their body weight and age during the 24-month treatment phase. After the 24-month treatment phase, participants who chose to enter the OLE phase continued receiving risdiplam, PO, QD, based on their body weight and age up to a maximum of 3 years.	AVXS-101 Participants previously treated with AVXS-101, received risdiplam, PO, QD, based on their body weight and age during the 24-month treatment phase. After the 24-month treatment phase, participants who chose to enter the OLE phase continued receiving risdiplam, PO, QD, based on their body weight and age up to a maximum of 3 years.
Maximum Plasma Concentration (Cmax) of Risdiplam	120 nanograms per milliliter (ng/mL) Interval 38.1 to 258.0	—	—	—

PRIMARY outcome

Timeframe: 24 hours Postdose at Year 2 Visit

Outcome measures

Outcome measures
Measure	RO6885247 n=122 Participants Participants previously treated with the splicing modifier, RO6885247 or placebo in study BP29420, received risdiplam, PO, QD, based on their body weight and age during the 24-month treatment phase. After the 24-month treatment phase, participants who chose to enter the OLE phase continued receiving risdiplam, PO, QD, based on their body weight and age up to a maximum of 3 years.	Nusinersen Participants previously treated with nusinersen, received risdiplam, PO, QD, based on their body weight and age during the 24-month treatment phase. After the 24-month treatment phase, participants who chose to enter the OLE phase continued receiving risdiplam, PO, QD, based on their body weight and age up to a maximum of 3 years.	Olesoxime Participants previously treated with olesoxime, received risdiplam, PO, QD, based on their body weight and age during the 24-month treatment phase. After the 24-month treatment phase, participants who chose to enter the OLE phase continued receiving risdiplam, PO, QD, based on their body weight and age up to a maximum of 3 years.	AVXS-101 Participants previously treated with AVXS-101, received risdiplam, PO, QD, based on their body weight and age during the 24-month treatment phase. After the 24-month treatment phase, participants who chose to enter the OLE phase continued receiving risdiplam, PO, QD, based on their body weight and age up to a maximum of 3 years.
Area Under the Concentration-Time Curve (AUC0-24h) of Risdiplam	1720 nanogramshour/milliliter (ngh/mL) Interval 983.0 to 2670.0	—	—	—

PRIMARY outcome

Timeframe: Predose at Year 5 visit

Outcome measures

Outcome measures
Measure	RO6885247 n=113 Participants Participants previously treated with the splicing modifier, RO6885247 or placebo in study BP29420, received risdiplam, PO, QD, based on their body weight and age during the 24-month treatment phase. After the 24-month treatment phase, participants who chose to enter the OLE phase continued receiving risdiplam, PO, QD, based on their body weight and age up to a maximum of 3 years.	Nusinersen Participants previously treated with nusinersen, received risdiplam, PO, QD, based on their body weight and age during the 24-month treatment phase. After the 24-month treatment phase, participants who chose to enter the OLE phase continued receiving risdiplam, PO, QD, based on their body weight and age up to a maximum of 3 years.	Olesoxime Participants previously treated with olesoxime, received risdiplam, PO, QD, based on their body weight and age during the 24-month treatment phase. After the 24-month treatment phase, participants who chose to enter the OLE phase continued receiving risdiplam, PO, QD, based on their body weight and age up to a maximum of 3 years.	AVXS-101 Participants previously treated with AVXS-101, received risdiplam, PO, QD, based on their body weight and age during the 24-month treatment phase. After the 24-month treatment phase, participants who chose to enter the OLE phase continued receiving risdiplam, PO, QD, based on their body weight and age up to a maximum of 3 years.
Plasma Trough Concentration (Ctrough) of Risdiplam	57.5 ng/mL Interval 17.7 to 168.0	—	—	—

SECONDARY outcome

Timeframe: Baseline and Year 5

Population: Pharmacodynamic (PD) population included all participants with at least one timepoint with a measurable PD marker. Overall number analyzed is the number of participants with data available for analysis.

SMA is caused by a homozygous deletion or mutation of the SMN 1 gene, which encodes SMN, an essential protein expressed in both neuronal and non-neuronal cells. In humans, there are two SMN genes, the SMN1 gene and its paralog SMN2. Risdiplam directly targets the underlying molecular deficiency of the disease and promotes the inclusion of exon 7 to generate full-length SMN2 mRNA, which therefore increases the production of functional SMN protein. As pre-specified in the protocol, the PD data were not to be compared between participants who received different prior treatments, but to analyze the PD parameters of risdiplam. Hence, PD data have been presented in a single arm group irrespective of prior therapies received by the participants in previous studies.

Outcome measures

Outcome measures
Measure	RO6885247 n=147 Participants Participants previously treated with the splicing modifier, RO6885247 or placebo in study BP29420, received risdiplam, PO, QD, based on their body weight and age during the 24-month treatment phase. After the 24-month treatment phase, participants who chose to enter the OLE phase continued receiving risdiplam, PO, QD, based on their body weight and age up to a maximum of 3 years.	Nusinersen Participants previously treated with nusinersen, received risdiplam, PO, QD, based on their body weight and age during the 24-month treatment phase. After the 24-month treatment phase, participants who chose to enter the OLE phase continued receiving risdiplam, PO, QD, based on their body weight and age up to a maximum of 3 years.	Olesoxime Participants previously treated with olesoxime, received risdiplam, PO, QD, based on their body weight and age during the 24-month treatment phase. After the 24-month treatment phase, participants who chose to enter the OLE phase continued receiving risdiplam, PO, QD, based on their body weight and age up to a maximum of 3 years.	AVXS-101 Participants previously treated with AVXS-101, received risdiplam, PO, QD, based on their body weight and age during the 24-month treatment phase. After the 24-month treatment phase, participants who chose to enter the OLE phase continued receiving risdiplam, PO, QD, based on their body weight and age up to a maximum of 3 years.
Survival of Motor Neuron (SMN) Protein Levels in Blood Baseline	3.35 ng/mL Interval 0.527 to 8.16	—	—	—
Survival of Motor Neuron (SMN) Protein Levels in Blood Year 5	6.51 ng/mL Interval 0.497 to 13.4	—	—	—

Adverse Events

RO6885247

Serious events: 3 serious events

Other events: 12 other events

Deaths: 0 deaths

Nusinersen

Serious events: 25 serious events

Other events: 76 other events

Deaths: 0 deaths

Olesoxime

Serious events: 24 serious events

Other events: 69 other events

Deaths: 0 deaths

AVXS-101

Serious events: 8 serious events

Other events: 14 other events

Deaths: 2 deaths

Serious adverse events

Other adverse events

Additional Information

Medical Communications

Hoffmann-La Roche

Phone: 800 821-8590

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
Publication restrictions are in place

Restriction type: OTHER