How Does Risdiplam Compare in Infantile-Onset Spinal Muscular Atrophy (SMA)? Preliminary Indirect Treatment Comparisons Based on FIREFISH Part 1 Data

How does risdiplam compare in infantile-onset spinal muscular atrophy (SMA)? Preliminary indirect treatment comparisons based on FIREFISH Part 1 data

Daigl M,1 Kotzeva A,1 Gorni K,1 Evans R,2 Hawkins N,2 Scott DA,2 Mahajan A,3 Baranello G,4,5 Servais L6,7

1F. Hoffmann-La Roche Ltd, Basel, Switzerland; 2Visible Analytics, Oxford, UK; 3Bridge Medical Consulting Ltd., London, UK; 4The Dubowitz Neuromuscular Centre, UCL Great Ormond Street Institute of Child Health, London, UK (current affiliation);5 Carlo Besta Neurological Research Institute Foundation, Developmental Neurology Unit, Milan, Italy; 6Division of Child Neurology, Neuromuscular Reference Center, Department of Pediatrics, University Hospital Liège, Belgium; 7MDUK Oxford Neuromuscular Centre, Oxford, UK.

Background Motor milestones analysis • In the last few years, innovative drugs have emerged for SMA and are being evaluated by • MAIC analysis of HINE-2 motor milestone response with risdiplam versus nusinersen gave an regulators, payers, and HTA bodies across the globe. OR of 5.79 (95% CI 0.98–46.19), while risdiplam versus BSC gave an OR of 379.71 (95% CI 75.19–1070.54) (Figure 2). ——None of these drugs have been compared in head-to-head trials. • In this analysis, indirect treatment comparison (ITC) evaluated the relative efficacy of risdiplam Figure 2. HINE-2 motor milestone response* against nusinersen (SPINRAZA®) or onasemnogene abeparvovec-xioi (ZOLGENSMA®) in patients with infantile-onset (Type 1) SMA. 100 • FIREFISH (NCT02913482) is an open-label, multicenter clinical study assessing the safety, 80 tolerability, pharmacokinetics, pharmacodynamics and efficacy of risdiplam in infants with infantile-onset SMA.1 60 ——Part 1: Dose-finding period followed by open-label extension. 40 ——Part 2: Efficacy and safety at the dose selected in Part 1. Responders, % • Individual patient data (IPD) from the 21 patients in the dose-finding Part 1 of the FIREFISH 20 study of risdiplam1 were included in this analysis. 0 Risdiplam Risdiplam Nusinersen BSC (FIREFISH (FIREFISH (ENDEAR) (ENDEAR) unadjusted) matching-adjusted Methods to ENDEAR) • Comparator studies were identified through a systematic literature review of published articles Comparator Unadjusted comparison MAIC and congress abstracts up to February 2018. (STUDY) Weighted number Responders/ OR for risdiplam OR for risdiplam ——Eight studies were identified across four compounds in infantile-onset SMA of responders/sum sample size against comparator† against comparator† (see additional material). of weights (% [95% CI]) (95% CI) (95% CI) ——Analyses were performed on the FIREFISH Part 1 study of risdiplam (NCT02913482),1 (% [95% CI]) 2 the ENDEAR study of nusinersen (NCT02193074) and the CL-101 study of onasemnogene Risdiplam 14/21 13.59/15.87 - - abeparvovec (NCT02122952).3 (FIREFISH Part 1) (67 [43–86]) (86 [70–100]) • Matching-adjusted indirect comparison (MAIC) is a population-adjusted method where IPD Nusinersen 37/73 1.95 37/73 5.79 from studies of one treatment are ‘weighted’ so that summary baseline characteristics match (ENDEAR) (51 [39–63]) (0.73–5.84) (51 [39–63]) (0.98–46.19) other studies.4 BSC 0/37 145.00 0/37 379.71 ——MAIC aims to adjust for imbalances between trials that may influence outcome. (ENDEAR sham control arm) (0 [0–9]) (57.00–396.43)‡ (0 [0–9]) (75.19–1070.54)‡ 5,6 • Data was extracted from published comparator manuscripts and digitized, before being *Infants were considered to have a motor milestone response if they met the following two criteria: (1) improvement in at least one category (i.e. an increase in the score for head control, rolling, sitting, crawling, standing, or walking of ≥1 point, an increase in the score for kicking of compared to FIREFISH Part 1 IPD. ≥2 points, or achievement of the maximal score for kicking) and (2) more categories with improvement than worsening (i.e. a decrease in the score for head control, rolling, sitting, crawling, standing, or walking of ≥1 point or a decrease in the score for kicking of ≥2 points). HINE-2 motor milestone achievement in infants is assessed at the latest of Days 183, 302 or 394 for patients in ENDEAR (stopped at interim)5 and at 12 months for FIREFISH Part 1. Infants who died or were withdrawn from the trial were considered to have no response regardless of length of follow-up. †OR >1 favors risdiplam over comparator. ‡OR calculated using the half-cell correction. Bootstrap CIs are calculated from N=1000 bootstrap Results samples for FIREFISH. Clopper Pearson CIs are used for ENDEAR. Baseline characteristics • MAIC analysis of sitting without support with risdiplam versus nusinersen gave an OR of 9.22 (95% CI 2.62–29.06), while risdiplam versus BSC gave an OR of 62.66 • SMN2 copy number, duration of symptoms, age at time of first dose, functional score at (95% CI 21.39–154.41) (Figure 3). baseline and ventilatory/nutritional support have been reported to influence outcomes.7–12 • Duration of symptoms, age at first dose and functional score at baseline were selected for the Figure 3. HINE-2 sitting without support (stable sits and pivots) matching based on expert clinicians’ opinion. 100 • All patients had two SMN2 gene copies (Table 1). 80 • Duration of symptoms was not reported in the CL-101 study.3,6 Age at symptom onset was used in the matching adjustment. 60

Table 1. Baseline characteristics before matching 40 Nusinersen and Onasemnogene Risdiplam Responders, % BSC abeparvovec Baseline characteristic (FIREFISH Part 1)1 20 (ENDEAR)2, 5 (CL-101)3,6 N=21 N=121 N=12 0 Risdiplam Risdiplam Nusinersen BSC Mean age at first dose, days 178 169 ~103* (FIREFISH (FIREFISH (ENDEAR) (ENDEAR) (SD [range]) (42 [102–213]) (NR [30–262]) (NR [27–240]) unadjusted) matching-adjusted to ENDEAR) Female gender, % 71 55 58 Comparator Unadjusted comparison MAIC White race, % 81 NR 92 (STUDY) Weighted number Responders/ OR for risdiplam † of responders/sum OR for risdiplam Mean age at symptom onset, weeks 8.1 8.5 ~6.1 sample size against comparator† † of weights against comparator (SD [range]) (3.2 [4–13.1]) (NR [1–20]) (NR [0–13]) (%; 95% CI) (95% CI) (95% CI) (%; 95% CI) Mean disease duration at screening, 104 ~94‡ NR Risdiplam 6/21 7.18/15.87 days (SD [range]) (38 [37–163]) (NR [0–181]) - - (FIREFISH) (29 [10–48]) (45; [18–72]) 14.1 14.3 ~8.6§ Mean age at diagnosis, weeks (SD [range]) Nusinersen 6/73 4.47 6/73 9.22 (5.8 [4–23.3]) (NR [0–30]) (NR [0–19]) (ENDEAR) (8 [3–17]) (1.18-10.15) (8; [3–17]) (2.62–29.06) CHOP-INTEND, mean score 24 27 28 BSC 0/37 31.45 0/37 62.66 (SD [range]) (6 [10–34]) (7.94 [NR]) (NR [12–50]) (ENDEAR sham control arm) (0 [0–9]) (9.62–68.48)‡ (0 [0–9]) (21.39–154.41)‡ Patients with nutritional support: Unable to 5 10 NR HINE-2 motor milestone achievement in infants is assessed at the latest of Days 183, 302 or 394 for patients in ENDEAR (stopped at interim)5 swallow/gastrointestinal tube feeding, % and at Day 365 for FIREFISH Part 1. Infants who died, or were withdrawn from the trial were considered to have no response regardless of length of follow-up. †OR>1 favors risdiplam over comparator; ‡OR calculated using the half-cell correction. Bootstrap CIs are calculated from N=1000 Patients with ventilatory support, % 24 22 17 bootstrap samples for FIREFISH. Clopper Pearson CIs are used for ENDEAR. 1.0 1.4 • ITC of adverse events (AEs) was not performed, however; HINE-2 score, mean (SD [range]) NR (0.7 [0–3]) (1.2 [NR]) ——as of February 2019, there have been no drug-related safety findings in FIREFISH Part 1 13 Proportion of patients with two copies leading to withdrawal of any patients 100 100 100 of SMN2, % ——AEs were reflective of the underlying disease.13 In ENDEAR, the incidence and severity 5 *3.4 months, †1.4 months, ‡13.2 weeks, §60 days. of AEs were similar in treatment and control groups. Matching factors are in bold. Treatment with risdiplam, nusinersen and onasemnogene abeparvovec are always undertaken in conjunction with BSC. The BSC population in this analysis is taken from the sham control arm of the ENDEAR study.5 MAIC analysis to compare with CL-101 (onasemnogene abeparvovec) • Matching the average characteristics of ENDEAR with FIREFISH Part 1 was successful. • MAIC of FIREFISH Part 1 versus CL-101 aggregate data was not feasible due to lack of overlap The ESS of FIREFISH Part 1 was reduced to 12.8 after matching (see supplementary material). of mean values and ranges. ——Matching FIREFISH Part 1 to CL-101 gave an ESS of 1.8 (see supplementary material). MAIC analyses to compare with ENDEAR (nusinersen) • An unadjusted (naïve) comparison would be expected to be biased in favor of onasemnogene Event-free survival* abeparvovec due to: ——younger age of patients at time of treatment initiation • MAIC of event-free survival comparing risdiplam (FIREFISH Part 1) with nusinersen (ENDEAR) or BSC (ENDEAR sham control arm) gave HRs of 0.23 (95% CI 0.00–0.66) and 0.11 ——differences in disease duration prior to treatment (95% CI 0.00–0.30), respectively (Figure 1; Table 2). ——greater CHOP-INTEND total scores at baseline. Figure 1. Kaplan–Meier curves for event-free survival*

Risdiplam Risdiplam (FIREFISH (FIREFISH Nusinersen BSC Conclusions unadjusted) matching-adjusted (ENDEAR) (ENDEAR) 1.00 to ENDEAR) • Preliminary results suggest that treatment of infantile-onset SMA with risdiplam may lead to longer event-free survival versus nusinersen, or BSC. • Risdiplam may also yield a better achievement of HINE-2 motor milestones versus nusinersen 0.75 or BSC alone. • Unadjusted ITC analyses comparing risdiplam with nusinersen or BSC gave similar results to MAIC analyses. 0.50 • Matching against onasemnogene abeparvovec was not feasible due to large differences in baseline factors that potentially influence outcomes. Limitations of MAIC 0.25 • Results will be biased if not all prognostic and predictive factors are included. Event-free survival probability • MAIC does not account for potential changes in standard of care over time. 0.00 • Analysis of HINE-2 milestones was at Day 365 for FIREFISH, versus the latest of Days 183, 302, 0 3 6 9 12 or 394 for ENDEAR (stopped at interim).5 Time (months) ——Sensitivity analyses using an earlier data cut from FIREFISH Part 1 (September 7th, 2018)14 ENDEAR Kaplan–Meier curves were extracted from Finkel RS, et al, 2017.5 For the purpose of this analysis, patients were censored at 13 months showed similar trends but with greater uncertainties (see supplementary material). (administrative censoring). *Event free-survival is defined as alive without permanent ventilation. In ENDEAR, permanent ventilation is defined as tracheostomy or ventilatory support for ≥16 hours per day for >21 continuous days in the absence of an acute reversible event. In FIREFISH, • MAICs lead to reductions in sample size due to the re-weighting process. This increases it is defined as tracheostomy or BiPAP ≥16 hours per day continuously for >3 weeks or continuous intubation >3 weeks, in the absence of, or uncertainty in the results. following the resolution of, an acute reversible event. Treatment with risdiplam and nusinersen is always undertaken in conjunction with BSC. The BSC population in this analysis is taken from the sham control arm of the ENDEAR study. • By matching to the comparator trial, the analysis assumes that this is the target population. Table 2. Comparison of event-free survival pre- and post-matching Comparator Unadjusted comparison MAIC Abbreviations (STUDY) HR for risdiplam Weighted number HR for risdiplam AE, adverse event; BiPAP, bilevel positive airway pressure; BSC, best supportive care; CHOP-INTEND, Children’s Hospital of Philadelphia Infant Test of Number of events/ against comparator* of events/sum against comparator* Neurological Disorders; CI, confidence interval; ESS, effective sample size; HINE-2, Hammersmith infant scales of development, second edition; sample size HR, hazard ratio; HTA, health technology assessment; IPD, individual patient data; ITC, indirect treatment comparison; MAIC, matching-adjusted indirect (95% CI) of weights (95% CI) comparison; NR, not reported; OR, odds ratio; SD, standard deviation; SMA, spinal muscular atrophy; SMN, survival of motor neuron. Risdiplam 3/21 - 2.26/15.87 - (FIREFISH Part 1) Nusinersen 0.25 0.23 Acknowledgments 31/80 31/80 The authors would like to thank the infants and their families for participation in the FIREFISH study, and the investigators and trial staff for administering (ENDEAR) (0.00–0.65) (0.00–0.66) the assessments and collecting the data. The study was sponsored by F. Hoffmann-La Roche AG, Basel, Switzerland. Writing and editorial assistance was provided by Lauren Walmsley, PhD, of MediTech Media, UK, in accordance with the Good Publication Practice (GPP3) guidelines (http://www.ismpp.org/gpp3). BSC 0.11 0.11 28/41 28/41 (ENDEAR sham control arm) (0.00–0.29) (0.00–0.30)

*HR <1 favors risdiplam over comparator. Bootstrap CIs are calculated from N=1000 bootstrap samples for FIREFISH. Clopper Pearson CIs are used for ENDEAR. References 1. ClinicalTrials.gov. NCT02913482. Accessed Sept 2019; 8. Rudnik-Schoneborn S, et al. Clin Genet. 2009; 76:168–178; 2. ClinicalTrials.gov. NCT02193074. Accessed Sept 2019; 9. Aragon-Gawinska K, et al. Neurology. 2018;91:e1312–e1318; 3. ClinicalTrials.gov. NCT02122952. Accessed Sept 2019; 10. Pechmann A, et al. J Neuromuscul Dis. 2018; 5:135–143; 4. Phillippo DM, et al. http://Nicedsu.org.uk/wp-content/uploads/2017/05/ 11. Oskoui M, et al. Neurology. 2007; 69:1931–1936; Please scan using your QR reader application to access the graphs and data presented in this poster. population-adjustment-TSD-FINAL.pdf. Accessed Sept 2019; 12. Ge X, et al. J Child Neurol. 2012; 27:471–477; NB: there may be associated costs for downloading data. These costs may be high if you are using your smartphone abroad. 5. Finkel RS, et al. N Engl J Med. 2017; 377:1723–1732; 13. Baranello G, et al. Data presented at Cure SMA 2019; Please check your mobile data tariff or contact your service provider for more details. 6. Mendell JR, et al. N Engl J Med. 2017; 377:1713–1722; 14. Baranello G, et al. Poster presented at WMS 2018. 7. Farrar MA, et al. J Pediatr. 2013; 162:155–159;

Presented at ISPOR Europe, Copenhagen, Denmark, 2–6 November 2019 How does risdiplam compare in infantile-onset spinal muscular atrophy (SMA)? Preliminary indirect treatment comparisons based on FIREFISH Part 1 data

Daigl M,1 Kotzeva A,1 Gorni K,1 Evans R,2 Hawkins N,2 Scott DA,2 Mahajan A,3 Baranello G,4,5 Servais L6,7

Supplementary Figure 1. MAIC analysis procedure1 Supplementary Table 3. MAIC analysis of HINE-2 motor milestone response in FIREFISH Part 1 (data cut Sept 7th, 2018)14 versus ENDEAR 1 3 4 ROCHE IPD is weighted so that Baseline characteristics Comparator Unadjusted comparison MAIC Comparator studies are identiﬁed selected baseline characteristics matched (STUDY) through a systematic literature review match the selected aggregate Weighted number Responders/ OR for risdiplam OR for risdiplam baseline characteristics reported Comparator ROCHE of responders/ sample size against comparator* against comparator* in the comparator study, e.g.: Product sum of weights 2 (%; 95% CI) (95% CI) (95% CI) Comparator ROCHE IPD (%; 95% CI) study Risdiplam 10/16 9.26/12.30 (published - - aggregate baseline 3.1 (FIREFISH Part 1) (63 [38–81]) (75 [44–100]) characteristics) 0.4 0.1 Recalculate IPD Nusinersen 37/73 1.62 37/73 2.97 outcomes using (ENDEAR) (51 [39–63]) (0.58–4.22) (51 [39–63]) (0.79–14.22) weights 0.5 0.2 BSC 0/37 121.15 0/37 207.20 2.9 (ENDEAR sham control arm) (0 [0–9]) (46.43–289.29)† (0 [0–9]) (62.60–617.96)†

compare recalculated *OR >1 favors risdiplam over comparator; †OR calculated using the half-cell correction. ROCHE Product 2.4 HINE-2 motor milestone achievement in infants is at the the latest available between Day 183 and 394. Infants who died or were withdrawn from the trial outcomes with published were considered to have no response regardless of length of follow-up. Similarity with 0.09 0.8 Comparator outcomes Average follow-up was 8 months for FIREFISH 7th Sept 2018 datacut14 and 9 months for ENDEAR (stopped at interim).5 comparator study: High Low Supplementary Table 4. MAIC analysis of HINE-2 sitting without support in FIREFISH Part 1 (data cut Sept 7th, 2018)14 vs ENDEAR Supplementary Table 1. Systematic literature review search results for clinical trials in infants with Type 1 SMA Comparator Unadjusted comparison MAIC (STUDY) Weighted number Trial name Compound Trial type Phase Current status Responders/ OR for risdiplam OR for risdiplam of responders/ sample size against comparator* against comparator* 2,3 sum of weights NCT01839656 Nusinersen DC/DE 2 Completed* (%; 95% CI) (95% CI) (95% CI) (%; 95% CI) ENDEAR4,5 Nusinersen RCT 3 Completed Risdiplam 3/16 5.40/12.30 - - EMBRACE6 Nusinersen RCT 2 Completed (FIREFISH Part 1) (19 [0–38]) (44 [0–74]) NURTURE7 Nusinersen SA 2 Ongoing Nusinersen 6/73 2.58 6/73 8.73 (ENDEAR) (8 [3–17]) (0.32–6.7) (8 [3–17]) (1.85–30.68) FIREFISH8 (Part 1) Risdiplam DC/DE 2 Ongoing BSC 0/37 19.44 0/37 59.72 8 Risdiplam SA 2 Ongoing FIREFISH (Part 2) (ENDEAR sham control arm) (0 [0–9]) (2.27–46.43)† (0 [0–9]) (18.01–173.95)†

Onasemnogene † CL-1019,10 DC/DE 1 Completed *OR >1 favors risdiplam over comparator; OR calculated using the half-cell correction. abeparvovec HINE-2 motor milestone achievement in infants is at the latest available between Day 183 and 394. Infants who died or were withdrawn from the trial were considered to have no response regardless of length of follow-up. Onasemnogene 11 OLE 1 Ongoing Average follow-up was 8 months for FIREFISH 7th Sept 2018 datacut14 and 9 months for ENDEAR (stopped at interim).5 START abeparvovec Supplementary Table 5. FIREFISH vs CL-101 population pre-and post-matching baseline Onasemnogene 12 SA 3 Ongoing† STR1VE abeparvovec patient characteristics

NCT0226855213 LMI070 (branaplam) SA 1/2 Ongoing Intervention (study) Mean age at Mean age at Mean total ESS first dose (days) symptoms onset CHOP-INTEND *Not considered in the MAIC analyses; †Results not publicly available at time of the analysis. Trials shaded in dark blue are completed. (days) score Supplementary Table 2. FIREFISH vs ENDEAR population pre- and post-matching baseline Risdiplam (FIREFISH Part 1) 21 178 57 23.6 patient characteristics Risdiplam 21 (1.8) 113 43 29.0 Mean age Mean Mean Mean total (CL-101 matching-adjusted) Female at first age at symptoms CHOP- Mean total Study ESS symptoms Onasemnogene abeparvovec (%) dose* onset duration* INTEND HINE-2 12 103 43 28 (days) (days) (days) score* (CL-101) Risdiplam 21 71 178 57 104 23.6 1.00 (FIREFISH) Risdiplam Abbreviations (ENDEAR 21 (12.8) 82 169 57 94 27.24 1.03 BSC, best supportive care; CI, confidence intervals; CHOP-INTEND, Children’s Hospital of Philadelphia Infant Test of Neurological Disorders; DC/DE, dose Re-Weighted) comparison/escalation; ESS, effective sample size; HINE-2, Hammersmith infant scales of development, second edition; HR, hazard ration; IPD, individual patient data; MAIC, matching-adjusted indirect comparison; OLE, open-label extension; OR, odds ratio; RCT, randomized clinical trial; SA, single arm. Nusinersen & 121 55 169 60 94 27.24 1.37 BSC(ENDEAR) * Matching factors References 1. Nash P, et al. Rheumatol Ther. 2018; 5:99–122; 8. Clinicaltrials.gov. NCT02913482. Accessed Sept 2019; 2. Clinicaltrials.gov. NCT01839656. Accessed Sept 2019; 9. Clinicaltrials.gov. NCT02913482. Accessed Sept 2019; Supplementary Figure 2. MAIC analysis of event-free survival* in FIREFISH Part 1 3. Finkel RS, et al. Lancet. 2016; 388:3017–3026; 10. Mendell JR, et al. N Engl J Med. 2017; 377:1713–1721; 4. Clinicaltrials.gov. NCT02193074. Accessed Sept 2019; 11. Clinicaltrials.gov. NCT03421977. Accessed Sept 2019; versus ENDEAR including numbers at risk data 5. Finkel RS, et al. N Engl J Med. 2017; 377:1723–1732; 12. Clinicaltrials.gov. NCT03306277. Accessed Sept 2019; 6. Clinicaltrials.gov. NCT02462759. Accessed Sept 2019; 13. Clinicaltrials.gov. NCT02268552. Accessed Sept 2019; Risdiplam Risdiplam Nusinersen BSC 7. Clinicaltrials.gov. NCT02386553. Accessed Sept 2019; 14. Baranello G, et al. Poster presented at WMS 2018. (FIREFISH (FIREFISH (ENDEAR) (ENDEAR) unadjusted) matching-adjusted 1.00 to ENDEAR)

0.75

0.50

0.25 Event-free survival probability

0.00 0 3 6 9 12 Time Treatment Number at risk Risdiplam 21 20 20 19 19 (FIREFISH unadjusted) Risdiplam (ENDEAR 16 15 15 15 15 matching-adjusted) Nusinersen 80 59 46 29 16 BSC 41 30 14 9 7

Supplementary Figure 3. MAIC analysis of overall survival in FIREFISH Part 1 versus ENDEAR Risdiplam Risdiplam Nusinersen BSC (FIREFISH (FIREFISH (ENDEAR) (ENDEAR) unadjusted) matching-adjusted to ENDEAR) 1.00

0.75

0.50

0.25 Overall survival probability

0.00 0 3 6 9 12 Time Treatment Number at risk Risdiplam (FIREFISH unadjusted) 21 20 20 19 19 Risdiplam (ENDEAR matching-adjusted) 16 15 15 15 15 Nusinersen 80 71 58 41 28 BSC 41 33 23 17 12

ENDEAR Kaplan–Meier curves are extracted from Finkel RS, et al. 2017.3 For the purpose of these analyses, patients were censored at 13 months (administrative censoring). *Event free-survival is defined as alive without permanent ventilation. In ENDEAR, permanent ventilation is defined as tracheostomy or ventilatory support for ≥16 hours per day for >21 continuous days in the absence of an acute reversible event. In FIREFISH, it is defined as tracheostomy or BiPAP ≥16 hours per day continuously for >3 weeks or continuous intubation >3 weeks, in the absence of, or following the resolution of, an acute reversible event. Treatment with risdiplam and nusinersen is always undertaken in conjunction with BSC. The BSC population in this analysis is taken from the sham control arm of the ENDEAR study. Comparator Unadjusted comparison MAIC (STUDY) HR for risdiplam Weighted number HR for risdiplam Number of events/ against comparator* of events/sum against comparator* sample size (95% CI) of weights (95% CI) Risdiplam 3/21 - 2.26/15.87 - (FIREFISH Part 1) Nusinersen 0.73 0.70 13/80 13/80 (ENDEAR) (0.00–1.84) (0.00–1.96) BSC 0.27 0.25 16/41 16/41 (ENDEAR sham control arm) (0.00–0.68) (0.00–0.71) *HR <1 favors risdiplam over comparator.

Presented at ISPOR Europe, Copenhagen, Denmark, 2–6 November 2019