Abstract Details

Title Update from SUNFISH Part 1: Safety, Tolerability and PK/PD from the Dose-Finding Study, Including Exploratory Efficacy Data in Patients with Type 2 or 3 Spinal Muscular Atrophy (SMA) Treated with Risdiplam (RG7916)

Topic Child Neurology and Developmental Neurology

Presentation(s) S25 - Child Neurology: Spinal Muscular Atrophy: Treatments and Outcomes (2:06 PM-2:17 PM)

Poster/Presentation
Number 007

Background

SMA is caused by reduced levels of survival of motor neuron (SMN) protein from deletions and/or mutations of the SMN1 gene. While SMN1 produces full-length SMN protein, a second gene, SMN2, produces low levels of functional SMN protein. Risdiplam (RG7916/RO7034067) is an investigational, orally administered, centrally and peripherally distributed small molecule that modulates SMN2 pre-mRNA splicing towards the production of full-length SMN2 mRNA to increase SMN protein levels.

Objective

To determine safety, tolerability and PK/PD in patients with Type 2 or 3 SMA who received risdiplam for the duration of the SUNFISH Part 1 dose-finding study, and exploratory efficacy data in patients treated for at least 1 year in Part 1.

Design/Methods

SUNFISH (NCT02908685) is an ongoing multicenter, double-blind, placebo-controlled, operationally seamless study (randomized 2:1, risdiplam:placebo) in patients aged 2–25 years, with Type 2 or 3 SMA. Part 1 (n=51) assesses safety, tolerability and PK/PD of different risdiplam dose levels. Pivotal Part 2 (n=180) is assessing the safety and efficacy of the risdiplam dose level that was selected based on results from Part 1.

Results SUNFISH Part 1 included patients of broad age ranges and clinical characteristics (functional level, scoliosis and contractures). To date, a sustained, >2-fold increase in median SMN protein versus baseline was seen after 1 year of risdiplam. Adverse events have been mostly mild, resolved despite ongoing treatment and reflect the underlying disease. No drug-related safety findings have led to withdrawal. Safety, tolerability and PK/PD will be presented from all patients in Part 1. Exploratory efficacy will be presented in patients treated for ≥1 year.

Conclusions To date, risdiplam has been shown to be well tolerated and leads to sustained increases in SMN protein. Despite not being designed and powered to detect efficacy, patients on risdiplam experienced improvement over 12 months on the Motor Function Measure versus natural history.

Authors/Disclosures
Ksenija Gorni PRESENTER	Dr. Gorni has received personal compensation for serving as an employee of Hoffman La Roche.
	No disclosure on file
Giovanni Baranello	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.
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.
	No disclosure on file
Jeppe Buchbjerg, PhD	No disclosure on file
	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
Christian Czech, PhD	No disclosure on file
	No disclosure on file
Omar Khwaja, MD	No disclosure on file

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