Abstract Details

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.

To determine the safety, tolerability and pharmacokinetic/pharmacodynamic (PD) relationship of risdiplam in non-naïve patients with spinal muscular atrophy (SMA).

JEWELFISH (NCT03032172) is a multicenter, open-label study of daily risdiplam in non-naïve patients with SMA (inclusion criteria aged 6 months–60 years at enrollment) who previously received RG7800 (RO6885247), nusinersen (SPINRAZA^®), olesoxime or onasemnogene abeparvovec-xioi (ZOLGENSMA^®).

The enrolled population (N=174) included a broad range of ages (1–60 years), SMA types (1–3), SMN2 copy numbers (1–4) and motor functions (non-sitters/sitters/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 previously received RG7800, 76 received nusinersen, 70 received olesoxime and 14 received onasemnogene abeparvovec. Risdiplam treatment led to a rapid and sustained, >2-fold increase in SMN protein levels compared with baseline (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 in JEWELFISH. The safety profile of risdiplam was consistent with the safety profile observed in treatment-naïve patients.

We will present 12-month safety, PD and exploratory efficacy data from JEWELFISH (data-cut: 29 January 2021).