P.114 SUNFISH parts 1 and 2: 3-year efficacy and safety of risdiplam in types 2 and 3 spinal muscular atrophy (SMA).

Spinal muscular atrophy (SMA) affects individuals with a broad age range and spectrum of disease severity. Risdiplam (EVRYSDI®) is a centrally and peripherally distributed, oral survival of motor neuron 2 (SMN2) pre-mRNA splicing modifier that has been approved in more than 70 countries worldwide. SUNFISH (NCT02908685) is a multicenter, two-part, randomized, placebo-controlled, double-blind study in patients with Types 2 and 3 SMA (inclusion criteria: 2–25 years at enrollment). Part 1 (N=51) assessed the safety, tolerability and pharmacokinetics/pharmacodynamics of different risdiplam dose levels in patients with Types 2 and 3 SMA (ambulant and non-ambulant). Part 2 (N=180) assessed the efficacy and safety of the Part 1-selected dose of risdiplam versus placebo in Type 2 and non-ambulant type 3 SMA. In part 2, participants were treated with risdiplam or placebo for 12 months; all participants then received risdiplam until month 24. At month 24, patients were offered the opportunity to enter the open-label extension phase. The primary outcome of Part 2 was met, showing a statistically significant difference in the change from baseline in 32-item motor function measure total score at month 12 in patients treated with risdiplam (n=120) versus placebo (n=60). The gains observed with risdiplam treatment at month 12 were maintained between months 12 and 36. At month 36, there were no treatment-related safety findings leading to withdrawal. Here we present 36-month efficacy and safety data from SUNFISH. SUNFISH is ongoing and will provide further long-term efficacy and safety data of risdiplam in a broad population of children, teenagers and adults with SMA. [ABSTRACT FROM AUTHOR]