FIREFISH Part 2: Efficacy and Safety of Risdiplam (RG7916) in Infants with Type 1 Spinal Muscular Atrophy (SMA) (1302)

Objective: To determine the efficacy and safety of risdiplam (RG7916) in infants with Type 1 spinal muscular atrophy (SMA) treated for 12 months during the confirmatory Part 2 of the FIREFISH 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: FIREFISH (NCT02913482) is an ongoing, multicenter, open-label study of risdiplam in infants aged 1–7 months at enrollment with Type 1 SMA and two SMN2 gene copies. FIREFISH Part 1 (n=21) assesses the safety, tolerability, pharmacokinetics and pharmacodynamics of different risdiplam dose levels (plus exploratory efficacy outcomes). In FIREFISH Part 1 there have been no drug-related safety findings leading to withdrawal from the study following ≤30 (median 19) months of treatment (data-cut: 2nd July 2019). The primary objective of confirmatory Part 2 (n=41) is to investigate the efficacy of risdiplam at the dose selected in Part 1. The primary efficacy endpoint is the proportion of infants sitting without support for 5 seconds after 12 months on treatment, as assessed by Item 22 of the Gross Motor Scale of the Bayley Scales of Infant and Toddler Development, third edition (BSID-III). Additional secondary endpoints will also be measured.

Results: Here we will report efficacy and safety data from the confirmatory Part 2 of the FIREFISH study in participants who have received treatment with risdiplam for a minimum of 12 months at the dose selected in Part 1.

Conclusions: Part 2 of FIREFISH will provide important data on the efficacy and safety of risdiplam in infants with Type 1 SMA.

Disclosure: 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. Baranello has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with AveXis and Roche. 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. Rose has nothing to disclose. 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. Xiong has nothing to disclose. Dr. Zanotelli has nothing to disclose. Dr. El-Khairi has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Roche Products Limited. Dr. El-Khairi holds stock and/or stock options in Roche Holding AG. 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. 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. 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. 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.