Spinal muscular atrophy (SMA) is a severe, progressive neuromuscular disease that 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 pre?mRNA splicing modifier that has been approved by the FDA for the treatment of patients with SMA aged 2 months and older.
SUNFISH (NCT02908685) is a multicenter, two-part, randomized (2:1, risdiplam: placebo), placebo-controlled, double-blind study in a broad population of 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 Types 2 and 3 SMA (ambulant and non-ambulant). Part 2 (N=180) assesses 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.
SUNFISH aims to determine the efficacy and safety of risdiplam in patients with Types 2 and 3 SMA who have received this treatment for 3 years (36 months).
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 or improved upon at Month 24. At Month 24, there were no treatment-related safety findings leading to withdrawal. We will present SUNFISH efficacy and safety data after 3 years of risdiplam treatment.
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.