Spinal muscular atrophy (SMA) is a severe, progressive neuromuscular disease caused by reduced levels of the survival of motor neuron (SMN) protein due to deletions and/or mutations of the SMN1 gene. A second SMN gene, SMN2, produces only low levels of functional SMN protein. Risdiplam is a centrally and peripherally distributed oral SMN2 pre-mRNA splicing modifier that increases levels of functional SMN protein. Risdiplam (EVRYSDI™) 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 Type 2/3 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 2/3 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. Individuals were treated with risdiplam or placebo for 12 months; all individuals then received risdiplam until Month 24. At Month 24, patients were offered the opportunity to enter the open-label extension phase.
To determine the efficacy and safety of risdiplam in patients with Type 2 and non-ambulant Type 3 SMA after 24 months of treatment.
In Part 2, the primary outcome of the study was met, showing a statistically significant difference in the change from baseline in 32-item Motor Function Measure total score at Month 12 between patients treated with risdiplam (N=120) and placebo (N=60). No treatment-related safety findings leading to withdrawal were reported. For the first time, we will present SUNFISH Part 2 efficacy and safety data after 24 months of treatment.
SUNFISH Part 2 is ongoing and will provide further long-term efficacy and safety data of risdiplam in a broad population of children, teenagers and adults.