Abstract Details

Title Pooled Safety Data from the Risdiplam Clinical Trial Development Program

Topic Child Neurology and Developmental Neurology

Presentation(s) Child Neurology and Developmental Neurology Posters (7:00 AM-5:00 PM)

Poster/Presentation
Number 067

Objective To determine the long-term safety profile of risdiplam in individuals with SMA who have participated in the risdiplam clinical development program.

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

The risdiplam clinical development program consists of four studies in a broad population of individuals with SMA:

FIREFISH (NCT02913482) is a two-part study assessing the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD) and efficacy in infants with Type 1 SMA (inclusion criteria 1–7 months at enrollment)
SUNFISH (NCT02908685) is a two-part study assessing the safety, tolerability, PK, PD and efficacy in patients with Type 2 or 3 SMA (inclusion criteria 2–25 years at enrollment)
JEWELFISH (NCT0302172) assesses the safety, tolerability, PK and PD in patients with SMA (inclusion criteria 6 months–60 years at enrollment) who previously received RG7800 (RO6885247), nusinersen (SPINRAZA^®), olesoxime or onasemnogene abeparvovec-xioi (ZOLGENSMA^®).
RAINBOWFISH (NCT03779334) assesses the efficacy, safety, PK and PD in infants (inclusion criteria birth to 6 weeks at first dose) with genetically diagnosed and presymptomatic SMA.

Results Pooled analyses from FIREFISH Parts 1 and 2, SUNFISH Parts 1 and 2 and JEWELFISH showed no treatment-related safety findings leading to withdrawal from risdiplam treatment for up to 39 months in 465 patients (data-cut: 15^th January 2020). Here we will present updated pooled safety analyses for the risdiplam studies.

Conclusions

This analysis will add to the understanding of the long-term safety profile of risdiplam.

Authors/Disclosures
Laurent Servais (John Radcliffe Hospital) PRESENTER	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.
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.
Enrico S. Bertini, MD (Bambino Gesu Hospital)	Dr. Bertini has received personal compensation for serving as an employee of Bambino Gesu' Children's Resesarch Hospital.
Claudia A. Chiriboga, MD, F�鶹��ýӳ�� (Columbia University)	Dr. Chiriboga has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Genentec. Dr. Chiriboga has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. The institution of Dr. Chiriboga has received research support from Roche. The institution of Dr. Chiriboga has received research support from Avexis/Novartis. The institution of Dr. Chiriboga has received research support from Biogen. The institution of Dr. Chiriboga has received research support from NIH. The institution of Dr. Chiriboga has received research support from Biohaven. The institution of Dr. Chiriboga has received research support from Genentec. Dr. Chiriboga has received publishing royalties from a publication 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.
John W. Day, MD, PhD (Stanford University School of Medicine)	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 Avidity. Dr. Day has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for PepGen. Dr. Day has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Epirium Bio. 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 Solid Biosciences. Dr. Day has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Muscular Dystrophy Association. The institution of Dr. Day has received research support from Astellas Pharma. 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 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. The institution of Dr. Day has received research support from AMO Pharma. The institution of Dr. Day has received research support from AnnJi. Dr. Day has received research support from CureSMA. The institution of Dr. Day has received research support from Muscular Dystrophy Association. The institution of Dr. Day has received research support from Ionis Pharmaceuticals. The institution of Dr. Day has received research support from NMD Pharma. The institution of Dr. Day has received research support from SMA Foundation. Dr. Day has received intellectual property interests from a discovery or technology relating to health care.
Nicholas Deconinck	Nicholas Deconinck has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Dyne. 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 biogen. Nicholas Deconinck has received publishing royalties from a publication relating to health care.
Dirk Fischer	The institution of Dirk Fischer has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Hoffmann La Roche AG. The institution of Dirk Fischer has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Hoffmann La Roche AG.
Nathalie M. Goemans, MD (University Hospitals Leuven)	Dr. Goemans has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Pfizer. Dr. Goemans has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Biogen. Dr. Goemans has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Roche. Dr. Goemans has received publishing royalties from a publication relating to health care.
Janbernd Kirschner	No disclosure on file
	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. 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 Biogen.
	No disclosure on file
Silvia Bader-Weder, MD (F. Hoffmann-La Roche)	Dr. Bader-Weder has received personal compensation for serving as an employee of F. Hoffmann - La Roche. Dr. Bader-Weder has received stock or an ownership interest from F. Hoffmann - La Roche.
Ksenija Gorni	Dr. Gorni has received personal compensation for serving as an employee of Hoffman La Roche.
Birgit Jaber	No disclosure on file
	No disclosure on file
Renata Scalco, MD (MRC Centre for Neuromuscular Diseases)	No disclosure on file
	No disclosure on file

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