To determine the efficacy and safety of risdiplam (EVRYSDI®) in patients with Types 2 and 3 SMA after 48 months of treatment.

SMA affects individuals with a broad age range and spectrum of disease severity. Risdiplam is a centrally and peripherally distributed, oral survival of motor neuron 2 (SMN2) pre-mRNA splicing modifier that has been approved in over 90 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: aged 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; participants then received risdiplam in a blinded manner until Month 24. At Month 24, patients were offered the opportunity to enter the open-label extension phase.

The primary endpoint (Part 2) of change from baseline in the 32-item Motor Function Measure (MFM32) total score in risdiplam (n=120) versus placebo (n=60) was met at Month 12. These increases in motor function were sustained in the second and third year after risdiplam treatment, as measured by changes in MFM32, Hammersmith Functional Motor Scale – Expanded, and Revised Upper Limb Module. At Month 36 (data-cut: 6 September 2021), there were no treatment-related safety findings leading to withdrawal from either SUNFISH Part 1 or 2. Here we present 48-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.