Pooled Safety Data from the Risdiplam (RG7916) Clinical Trial Development Program (1267)

Objective: To describe the longer-term safety profile of risdiplam (RG7916) in individuals who have participated in the FIREFISH, SUNFISH, JEWELFISH and RAINBOWFISH studies. Background: Spinal muscular atrophy (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: The risdiplam clinical development program consists of four studies in a broad population of individuals with SMA: FIREFISH (NCT02913482) aims to assess the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD) and efficacy of risdiplam in infants with Type 1 SMA aged 1–7 months SUNFISH (NCT02908685) aims to evaluate the safety, tolerability, PK/PD and efficacy of risdiplam in patients with Type 2 or 3 SMA aged 2–25 years JEWELFISH (NCT03032172) aims to assess the safety, tolerability and PK/PD of risdiplam in patients with SMA aged 6 months–60 years previously enrolled in Study BP29420 (MOONFISH) with the splicing modifier RG7800 (RO6885247) or who received previous treatment with nusinersen (SPINRAZA®), olesoxime or onasemnogene abeparvovec-xioi (ZOLGENSMA®) RAINBOWFISH (NCT03779334) aims to investigate the efficacy, safety and PK/PD of risdiplam in newborns aged from birth to 6 weeks with genetically diagnosed and presymptomatic SMA. Results: Previous analyses from FIREFISH Part 1, SUNFISH Part 1 and JEWELFISH have shown no drug-related safety findings leading to withdrawal from treatment following risdiplam treatment for up to 32.3 months in 158 patients (data-cut: 28th June 2019 for FIREFISH, SUNFISH and JEWELFISH). We will present pooled safety analyses from FIREFISH Parts 1 and 2, SUNFISH Part 1 and JEWELFISH. Conclusions: This analysis will add to the understanding of the longer-term safety profile of risdiplam. Disclosure: Dr. Baranello has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with AveXis and Roche. Dr. Bertini has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Advisor/consultant for AveXis, Biogen, Edison, Novartis and Roche. Dr. Bertini has received research support from Grants from Fondazione Telethon and the Italian Ministry of Health. Dr. Chiriboga 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, Cytokinetics, Genentech, Ionis Pharmaceuticals, Inc., and Roche; educational speaker fees from Biogen.. Dr. Chiriboga has received research support from Grants from AveXis, Biogen, Ionis Pharmaceuticals, Inc., Roche, National Institutes of Health, and SMA Foundation.. Dr. Darras has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with AveXis, Biogen, Bristol-Myers Squibb, Cytokinetics, Marathon, PTC Therapeutics, Roche, Santhera, and Sarepta. Dr. Darras has received research support from the National Institutes of Health/National Institute of Neurological Disorders and Stroke, the Slaney Family Fund for SMA, Working on Walking Fund, the SMA Foundation; CureSMA, Ionis Pharmaceuticals, Inc. and Biogen, AveXis, Cytokinetics, Fibrogen, PTC Th. 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.. 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. Fischer has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Hoffmann La Roche. Dr. Goemans has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Sarepta, Pfizer, and Roche. Dr. Kirschner 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. Kirschner has received research support from Research grant from Avexis, Biogen, PTC, Roche, Santhera, and Sarepta.. Dr. Klein has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Speaker and consultancy fess from Santhera, PTC, Sarepta and Biogen. Dr. Masson has nothing to disclose. Dr. Mazurkiewicz-Beldzin has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Biogen and Biomarin. Dr. Servais has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Avexis, Inc., Biogen, Biophytis, Cytokinetics, Dynacure, Roche, Santhera, Sarepta Therapeutics. Dr. Servais has received research support from Avexis, Inc., Biogen, Dynacure, and Roche. Dr. Wang has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Medimagemetric LLC. Dr. Wang holds stock and/or stock options in Medimagemetric LLC. 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. 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. Jaber has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Hoffmann-La Roche. Dr. McIver has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Hoffmann-La Roche. Dr. Scalco has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Hoffmann-La Roche. Dr. Scalco holds stock and/or stock options in Hoffmann-La Roche which sponsored research in which Dr. Scalco was involved as an investigator. Dr. Scalco has received research support from Hoffmann-La Roche. 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..