Abstract Details

Title FIREFISH Parts 1 and 2: 24-month Safety and Efficacy of Risdiplam in Type 1 SMA

Topic Child Neurology and Developmental Neurology

Presentation(s) S39 - Child Neurology and Developmental Neurology (4:18 PM-4:30 PM)

Poster/Presentation
Number 005

Background Risdiplam (EVRYSDI^®) is a centrally and peripherally distributed, oral survival of motor neuron 2 (SMN2) pre-mRNA splicing modifier that has been approved by the FDA for the treatment of patients with SMA, aged ≥2 months.

Objective

To determine the efficacy and safety of risdiplam in infants with Type 1 spinal muscular atrophy (SMA) after 24 months of treatment.

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, aged 1–7 months at enrollment. Part 1 assessed the safety, tolerability and pharmacokinetics/pharmacodynamics of different risdiplam dose levels (low-dose cohort, n=4; high-dose cohort, n=17). Part 2 (N=41) assesses the efficacy and safety of risdiplam at the dose selected from Part 1. Parts 1 and 2 had the same inclusion/exclusion criteria.

Results

The Part 2 primary endpoint at Month 12 was met: 29% (12/41) of infants were able to sit without support for ≥5 seconds, as measured by the Gross Motor Scale of the Bayley Scales of Infant and Toddler Development, Third Edition (Item 22; P<0.0001, performance criterion=5%).

Previously, we presented pooled safety and efficacy data from 58 infants in Part 1 (high-dose cohort, n=17) and Part 2 (N=41) who received risdiplam for ≥12 months. At Month 12, 88% (51/58) of infants were alive without permanent ventilation. There were no treatment-related adverse events leading to withdrawal. Infants showed improvement in motor functions and achieved motor milestones, not observed in natural history.

Here, we present pooled FIREFISH data, from infants who have received risdiplam for ≥24 months.

Conclusions

The safety and efficacy of risdiplam are consistent between FIREFISH Parts 1 and 2. Parts 1 and 2 are ongoing globally and will provide further data on the long-term safety and efficacy of risdiplam in infants with Type 1 SMA.

Authors/Disclosures
John W. Day, MD, PhD (Stanford University School of Medicine) PRESENTER	Dr. Day has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Affinia Therapeutics. Dr. Day has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis Gene Therapy. Dr. Day has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen. Dr. Day has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche/Genentech. Dr. Day has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sarepta. Dr. Day has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Scholar Rock. Dr. Day has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Avidity. Dr. Day has received personal compensation in the range of $10,000-$49,999 for serving as an officer or member of the Board of Directors for Muscular Dystrophy Association. The institution of Dr. Day has received research support from Audentes. The institution of Dr. Day has received research support from Novartis Gene Therapy. The institution of Dr. Day has received research support from Biogen. The institution of Dr. Day has received research support from Cytokinetics. The institution of Dr. Day has received research support from Roche/Genentech. The institution of Dr. Day has received research support from Sanofi/Genzyme. The institution of Dr. Day has received research support from Sarepta. The institution of Dr. Day has received research support from Scholar Rock. Dr. Day has received intellectual property interests from a discovery or technology relating to health care.
Basil T. Darras, MD (Children'S Hosp Boston Harvard Med School)	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.
	No disclosure on file
Nicholas Deconinck	Nicholas Deconinck has received personal compensation in the range of $500-$4,999 for serving as a Consultant for biogen. Nicholas Deconinck has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for roche. Nicholas Deconinck has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for avexis. Nicholas Deconinck has received publishing royalties from a publication relating to health care.
	No disclosure on file
	No disclosure on file
Maria Mazurkiewicz-Beldzin (Medical University of Gdansk)	Dr. Mazurkiewicz Beldzin has received personal compensation in the range of $0-$499 for serving as a Consultant for Biogen, . Dr. Mazurkiewicz Beldzin has received personal compensation in the range of $0-$499 for serving as a Consultant for Novartis. Dr. Mazurkiewicz Beldzin has received personal compensation in the range of $0-$499 for serving as a Consultant for Roche. Dr. Mazurkiewicz Beldzin has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. Dr. Mazurkiewicz Beldzin has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis.
	No disclosure on file
	No disclosure on file
Laurent Servais (John Radcliffe Hospital)	Laurent Servais has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Biogen. Laurent Servais has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Roche. Laurent Servais has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Novartis. Laurent Servais has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Astellas. Laurent Servais has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Pfizer. Laurent Servais has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sarepta. The institution of Laurent Servais has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Evox. Laurent Servais has received personal compensation in the range of $500-$4,999 for serving as a Consultant for PTC. Laurent Servais has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Sysnav. Laurent Servais has received personal compensation in the range of $500-$4,999 for serving as a Consultant for BioHaven. Laurent Servais has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Dyne. Laurent Servais has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Zentech. Laurent Servais has received personal compensation in the range of $500-$4,999 for serving as a Consultant for MitoRx. Laurent Servais has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Lupin. Laurent Servais has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Fibrogen. Laurent Servais has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alltrana. Laurent Servais has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Illumina. Laurent Servais has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. The institution of Laurent Servais has received research support from Roche. The institution of Laurent Servais has received research support from Novartis. The institution of Laurent Servais has received research support from Biogen. The institution of Laurent Servais has received research support from Zentech. The institution of Laurent Servais has received research support from BioHaven. The institution of Laurent Servais has received research support from PerkinHalmers. The institution of Laurent Servais has received research support from Scholar Rock.
Dmitry Vlodavets	No disclosure on file
Hui Xiong	No disclosure on file
Edmar Zanoteli	Edmar Zanoteli has nothing to disclose.
Angela Dodman (F.Hoffmann-La Roche Ltd)	Angela Dodman has received personal compensation for serving as an employee of F. Hoffman-La Roche Ltd.
	No disclosure on file
Eleni Gaki, MD (Roche Product Ltd)	Dr. Gaki has received personal compensation for serving as an employee of Roche. Dr. Gaki has received stock or an ownership interest from Roche Products Ltd.
	No disclosure on file
Ksenija Gorni	Dr. Gorni has received personal compensation for serving as an employee of Hoffman La Roche.
Heidemarie Kletzl	Heidemarie Kletzl has received personal compensation for serving as an employee of Hoffmann-La Roche.
Giovanni Baranello	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.