Abstract Details

Title RG7916 significantly increases SMN Protein in SMA Type 1 Babies

Topic Child Neurology and Developmental Neurology

Presentation(s) ES1 - (-)

Poster/Presentation
Number 004

Objective

Background SMA is a severe, progressive, inherited disease that leads to loss of motor function and is the leading genetic cause of mortality in infants and toddlers. SMA is caused by reduced levels of SMN protein due to deletions or mutations of the survival of motor neuron 1 (SMN1) gene and alternative splicing of a related SMN2 gene. The published median time to death or permanent ventilation in Type 1 patients with two SMN2 gene copies is 10.5 months of age (Finkel, Neurology 2014). RG7916 is an orally administered, centrally and peripherally distributed small molecule that modulates SMN2 pre-mRNA splicing to increase SMN protein.

Design/Methods The exploratory Part 1 (n=8–24) of the FIREFISH study assesses safety, tolerability, pharmacokinetics and pharmacodynamics of RG7916 at different dose levels. The confirmatory Part 2 (n=40) will assess safety and efficacy of RG7916.

Results A dose-dependent increase in SMN protein levels in blood was observed, with an up to 6.5 -fold increase versus baseline after 4 weeks of treatment at the highest dose of RG7916 (range 2.0 – 6.5). To date, no safety-related stopping rules have been met, and while follow up was limited, no patient lost the ability to swallow, required tracheostomy, or reached permanent ventilation. Updated survival data will be presented.

Conclusions The up to 6.5-fold increase in SMN protein observed in FIREFISH Part 1 compares favorably with the approximately 2-fold difference in SMN protein levels between SMA severity types (e.g., Type 2 vs. Type 1). All doses explored so far have been well tolerated. FIREFISH is currently recruiting globally.

Authors/Disclosures
Giovanni Baranello	No disclosure on file
Heidemarie Kletzl	Heidemarie Kletzl has received personal compensation for serving as an employee of Hoffmann-La Roche.
	No disclosure on file
	No disclosure on file
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.
	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.
Nicholas Deconinck	Nicholas Deconinck has received personal compensation in the range of $500-$4,999 for serving as a Consultant for novartis. 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.
	No disclosure on file
	No disclosure on file
Christian Czech, PhD	No disclosure on file
Abdulsalam Alsuliman, MD, PhD	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
Ksenija Gorni	Dr. Gorni has received personal compensation for serving as an employee of Hoffman La Roche.
Omar Khwaja, MD	No disclosure on file

��ɫ��

��ɫ��