SUNFISH Part 2: Efficacy and Safety of Risdiplam (RG7916) in Patients with Type 2 or Non-Ambulant Type 3 Spinal Muscular Atrophy (SMA)

Objective: To determine the safety and efficacy of risdiplam (RG7916) in patients with Type 2 or non-ambulant Type 3 spinal muscular atrophy (SMA) treated for 12 months during confirmatory Part 2 of the SUNFISH study. Background: SMA is a severe, progressive neuromuscular disease caused by reduced levels of survival of motor neuron (SMN) protein due to deletions and/or mutations of the SMN1 gene. A second gene, SMN2, produces only low levels of functional SMN protein. Risdiplam is an orally administered, centrally and peripherally distributed SMN2 pre-mRNA splicing modifier that increases the levels of functional SMN protein. Design/Methods: SUNFISH (NCT02908685) is a multicenter, two-part, randomized, placebo-controlled, double-blind study (randomized 2:1, risdiplam:placebo) in patients, aged 2–25 years, with Type 2 or Type 3 SMA. SUNFISH is comprised of two parts: Part 1 (n=51) is a dose-selection study assessing the safety, tolerability and pharmacokinetics/pharmacodynamics of different risdiplam dose levels in patients with Type 2 and Type 3 SMA (ambulant and non-ambulant); confirmatory Part 2 (n=180) assesses the safety and efficacy of the risdiplam dose level that was selected from Part 1 compared with placebo in patients with Type 2 and non-ambulant Type 3 SMA. The primary objective of Part 2 is to evaluate the efficacy of risdiplam compared with placebo in terms of motor function as assessed by the change from baseline in the 32-item Motor Function Measure total score at Month 12. Results: In SUNFISH Part 1, no drug-related safety findings led to withdrawals from the study following 1 year of treatment with risdiplam (data-cut: 28th June 2019). Here we will report data from confirmatory Part 2 of the SUNFISH study including baseline demographics, safety and efficacy data in participants who have received treatment with risdiplam or placebo for 12 months. Conclusions: Part 2 of SUNFISH is currently ongoing. Disclosure: Dr. Mercuri has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Advisory boards for SMA studies for AveXis, Biogen, Ionis Pharmaceuticals, Inc., Novartis, and Roche.. Dr. Mercuri has received research support from Principal Investigator for ongoing Biogen/Ionis Pharmaceuticals, Inc. and Roche clinical trials; support from Biogen for a natural history registry; funding from Famiglie SMA Italy, Italian Telethon, and SMA Europe.. Dr. Barisic has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Medis Croatia (representative of Nusinersen for Croatia). Dr. Boespflug-Tanguy has nothing to disclose. Dr. Deconinck has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Advisory boards for Sarepta, Biomarin, Summit, Roche, Biogen and Novartis. Dr. Kostera-Pruszczyk has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Biogen, PTC, ARGENX, Sanofi. Dr. Kostera-Pruszczyk has received research support from Sanofi, Kedrion, Biogen, Shire. Dr. Masson has nothing to disclose. Dr. Mazzone has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Biogen, Roche, Avexis, Audentes, Scholar Rock. Dr. Nascimento Osorio has nothing to disclose. Dr. Saito has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Advisory boards for Biogen, Roche/Chugai and Novartis Pharma; Consultant for AveXis.. Dr. Saito has received research support from Research funding from Biogen, Roche/Chugai and AveXis.. Dr. Vlodavets has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with PTC therapeutics, Roche, Novartis, Sarepta Therapeutics, Avexus, Jannses, MARLIN Biotech. Dr. Vuillerot has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with PTC therapeutics; Biogen; Avexis; Roche. Dr. Vuillerot has received research support from Roche. Dr. Fuerst-Recktenwald has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with F. Hoffmann-La Roche Ltd.. Dr. Fuerst-Recktenwald holds stock and/or stock options in F. Hoffmann-La Roche Ltd. which sponsored research in which Dr. Fuerst-Recktenwald was involved as an investigator. Dr. Fuerst-Recktenwald holds stock and/or stock options in F. Hoffmann-La Roche Ltd.. Dr. Fuhrer holds stock and/or stock options in Roche employee – holding Roche shares which sponsored research in which Dr. Fuhrer was involved as an investigator. Dr. Gerber has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Hoffmann-La Roche. Dr. Gerber has received compensation for serving on the Board of Directors of Sponsor. Dr. Gerber holds stock and/or stock options in Hoffmann-La Roche which sponsored research in which Dr. Gerber was involved as an investigator. Dr. Gerber holds stock and/or stock options in Hoffmann-La Roche. Dr. Gorni has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with F.Hoffmann-La Roche. Dr. Kletzl has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Hoffmann-La Roche. Dr. Kletzl holds stock and/or stock options in Hoffmann-La Roche which sponsored research in which Dr. Kletzl was involved as an investigator. Dr. Kletzl holds stock and/or stock options in Hoffmann-La Roche. Dr. Kletzl has received research support from Hoffmann-La Roche. Dr. Martin has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Hoffmann-La Roche. Dr. Yeung has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Roche Products Ltd. Dr. Day has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Consultant for AMO Pharma, AveXis, Biogen, Cytokinetics, Ionis Pharmaceuticals, Inc., Pfizer, Roche, Santhera, Sarepta.. Dr. Day has received royalty, license fees, or contractual rights payments from Patents licensed to Athena Diagnostics for genetic testing of myotonic dystrophy type 2 (US patent 7442782) and spinocerebellar ataxia type 5 (US patent 7527931). Dr. Day has received research support from Grants from AMO Pharma, aTyr, AveXis, Biogen, Bristol-Myers Squibb, Cytokinetics, Ionis Pharmaceuticals, Inc., Roche, Sanofi-Genzyme, Sarepta..