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 (EVRYSDI®) is a centrally and peripherally distributed, oral SMN2 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, placebo-controlled, double-blind study in a broad population of patients with Type 2/3 SMA aged 2–25 years at enrollment. Part 1 (N=51) assessed the safety, tolerability and pharmacokinetics/pharmacodynamics of different risdiplam dose levels in Type 2/3 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, when patients were offered the opportunity to enter the open-label extension phase.
To compare 24-month efficacy results from SUNFISH Part 2 with data from an external control.
The primary outcome of Part 2 – change from baseline to Month 12 in the 32-item Motor Function Measure total score in patients treated with risdiplam (n=120) versus placebo (n=60) – was met. Here, we report the results of an analysis that compares data from patients in SUNFISH Part 2 who have been treated with risdiplam for 24 months with an external comparator dataset. The external comparator comprises data from the NatHis-SMA study (NCT02391831), a prospective, longitudinal natural history study of patients with Type 2/3 SMA, and from participants in the placebo arm of a Phase 2 study of olesoxime in patients with SMA (NCT01302600).
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.