SMA – THERAPY: P.263 SUNFISH Part 1: 24-month safety and exploratory outcomes of risdiplam (RG7916) treatment in patients with Type 2 or 3 spinal muscular atrophy (SMA)

Abstract

Spinal muscular atrophy (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 gene, SMN2, produces only low levels of functional SMN protein. Risdiplam (RG7916) is a centrally and peripherally distributed oral SMN2 pre-mRNA splicing modifier that increases the levels of functional SMN protein. SUNFISH (NCT02908685) is a multicenter, two-part, randomized, placebo-controlled, double-blind study (randomized 2:1, risdiplam:placebo) in a broad population of patients with Type 2 or 3 SMA, aged 2–25 years. Part 1 (n=51) assesses the safety, tolerability and pharmacokinetics/pharmacodynamics (PK/PD) of different risdiplam dose levels in patients with Type 2/3 SMA (ambulant and non-ambulant); confirmatory Part 2 (n=180) assesses the safety and efficacy of the Part 1-selected dose of risdiplam in patients with Type 2/non-ambulant Type 3 SMA. There have been no treatment-related safety findings leading to withdrawal in any risdiplam trial (data-cut: 28th June 2019). In SUNFISH Part 1 (data-cut: 9th Jan 2019) risdiplam treatment led to a median >2-fold increase in blood SMN protein levels after 4 weeks, which was sustained for ≥12 months. Treatment with the pivotal dose of risdiplam for ≥12 months also led to improvements in motor function versus natural history (data-cut: 9th Jan 2019). Safety, tolerability and PK/PD data will be reported from patients in Part 1 who have received risdiplam treatment for ≥24 months (data-cut: 15th Jan 2020). Updated Part 1 exploratory efficacy data, including motor outcome measures, will also be presented. The clinical benefit of risdiplam is being assessed in Part 2, which met its primary endpoint of change from baseline in the 32-item Motor Function Measure after 1 year of risdiplam treatment, compared to placebo (data-cut: 6th Sept 2019). SUNFISH Parts 1 and 2 are ongoing globally.