Abstract Details

Risdiplam is a centrally and peripherally distributed, oral survival of motor neuron 2 (SMN2) pre-mRNA splicing modifier that has been approved by the FDA for the treatment of patients with SMA, aged ≥2 months.

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.

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. Here we will present efficacy and safety data from patients who have received risdiplam treatment for 36 months.

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.