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 (SMN2) pre?mRNA splicing modifier that has been approved by the FDA for the treatment of patients with SMA aged 2 months and older.
JEWELFISH (NCT03032172) is a multicenter, open-label study of daily risdiplam in non-naïve patients with SMA (inclusion criteria aged 6 months to 60 years at enrollment) who had previously received RG7800 (RO6885247), nusinersen (SPINRAZA®), olesoxime or onasemnogene abeparvovec (ZOLGENSMA®).
JEWELFISH (N=174) assesses the safety, tolerability and pharmacokinetic/pharmacodynamic (PD) relationship of risdiplam in non-naïve patients.
The enrolled population included a broad range of ages (1–60 years), SMA types (1–3), SMN2 copy numbers (1–4) and motor functions (non-sitters, sitters and walkers). We previously presented safety data from 173 patients (data-cut: 31 July 2020) who received risdiplam for up to 41 months. One patient withdrew from the study at baseline; of the remaining patients, 13 had previously received RG7800, 76 had received nusinersen, 70 had received olesoxime and 14 had received onasemnogene abeparvovec. Risdiplam treatment led to a rapid and sustained >2-fold increase in SMN protein levels compared with baseline levels (data-cut: 1 June 2020), which was consistent with PD data from the SUNFISH study of treatment-naïve patients with Types 2/3 SMA. No drug-related safety findings leading to withdrawal were reported for any patient exposed to risdiplam in JEWELFISH. The safety profile of risdiplam was consistent with the safety profile observed in treatment-naïve patients.
Here we will present 12-month safety, PD and exploratory efficacy data from JEWELFISH (data-cut: 29 January 2021).
The JEWELFISH study is ongoing at sites across Europe and the US and will provide important data on the safety, PD and exploratory efficacy of risdiplam in a broad population of non-naïve patients with SMA.