FIREFISH Part 2: 24-month Efficacy and Safety of Risdiplam in Infants with Type 1 Spinal Muscular Atrophy (SMA) (4126)

Objective: To determine the efficacy and safety of risdiplam in infants with Type 1 spinal muscular atrophy (SMA) after 24 months of treatment. 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 SMN gene, SMN2, produces only low levels of functional SMN protein. Risdiplam is a centrally and peripherally distributed oral SMN2 pre-mRNA splicing modifier that increases the levels of functional SMN protein. Risdiplam (EVRYSDI™) has been approved by the FDA for the treatment of patients with SMA, aged 2 months and older. Design/Methods: FIREFISH (NCT02913482) is a multicenter, open-label, two-part study of risdiplam in infants with Type 1 SMA and two SMN2 gene copies (inclusion criteria 1–7 months at enrollment). Part 1 (N=21) assesses the safety, tolerability and pharmacokinetics/pharmacodynamics of different risdiplam dose levels. Pivotal Part 2 (N=41) assesses the efficacy and safety of the Part 1-selected dose of risdiplam. Results: The primary endpoint of Part 2 at 12 months was met (data-cut: 14th November 2019); 29% (P For the first time, we will present efficacy and safety data from infants in Part 2 who have received risdiplam treatment for 24 months. Conclusions: Part 2 is ongoing and will provide important data on the long-term efficacy and safety of risdiplam in infants with Type 1 SMA. Disclosure: The institution of Dr. Darras has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Amicus. Dr. Darras has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Amicus. The institution of Dr. Darras has received research support from National Institutes of Health/National Institute of Neurological Disorders and Stroke,. The institution of Dr. Darras has received research support from Slaney Family Fund for SMA. The institution of Dr. Darras has received research support from Spinal Muscular Atrophy Foundation. The institution of Dr. Darras has received research support from CureSMA. The institution of Dr. Darras has received research support from Working on Walking Fund . The institution of Dr. Darras has received research support from CHERISH, CS2/CS12 . The institution of Dr. Darras has received research support from Biogen for CS11. The institution of Dr. Darras has received research support from AveXis. The institution of Dr. Darras has received research support from Sarepta Pharmaceuticals. The institution of Dr. Darras has received research support from PTC Therapeutics. The institution of Dr. Darras has received research support from Roche. The institution of Dr. Darras has received research support from Santhera. The institution of Dr. Darras has received research support from Scholar Rock. The institution of Dr. Darras has received research support from Fibrogen. The institution of Dr. Darras has received research support from Summit. Dr. Darras has received publishing royalties from a publication relating to health care. Dr. Darras has received publishing royalties from a publication relating to health care. Ricardo Masson has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Roche, Biogen, Avexis. Ricardo Masson has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche, Biogen, Avexis. Maria Mazurkiewicz Beldzin has nothing to disclose. Kristy Rose has nothing to disclose. Hui Xiong has nothing to disclose. Edmar Zanoteli has nothing to disclose. Giovanni Baranello has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Roche. Giovanni Baranello has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Roche. Giovanni Baranello has received personal compensation in the range of $500-$4,999 for serving as a Consultant for AveXis. Giovanni Baranello has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. Giovanni Baranello has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for AveXis. Giovanni Baranello has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Roche. Giovanni Baranello has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for AveXis. The institution of Giovanni Baranello has received research support from Great Ormond Street Hospital Charity. Dmitry Vlodavets has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for AveXis. Dmitry Vlodavets has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche . Dmitry Vlodavets has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. Dmitry Vlodavets has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Janssen. Dmitry Vlodavets has received personal compensation in the range of $0-$499 for serving on a Speakers Bureau for Novartis. Dmitry Vlodavets has received personal compensation in the range of $0-$499 for serving on a Speakers Bureau for Roche. Dmitry Vlodavets has received personal compensation in the range of $0-$499 for serving on a Speakers Bureau for PTC Therapeutics. Dmitry Vlodavets has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Roche. Dmitry Vlodavets has received personal compensation in the range of $0-$499 for serving on a Speakers Bureau for PTC Therapeutics. Dmitry Vlodavets has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Roche. Angela Dodman has received personal compensation for serving as an employee of F. Hoffman-La Roche Ltd. Muna El-Khairi has received personal compensation for serving as an employee of Roche Products Limited. Marianne Gerber has received personal compensation for serving as an employee of Roche. Marianne Gerber has received stock or an ownership interest from F Hoffmann La Roche . Dr. Gorni has received personal compensation for serving as an employee of Hoffman La Roche. Heidemarie Kletzl has received personal compensation for serving as an employee of Hoffmann-La Roche. Laurent Servais has nothing to disclose.