185 JEWELFISH: Safety, pharmacodynamic and exploratory efficacy data in non-naïve patients with SMA receiving risdiplam

Risdiplam (EVRYSDI®) is an oral survival of motor neuron 2 (SMN2) pre-mRNA splicing modifier approved by the EMA and MHRA for the treatment of patients aged ≥2 months, with a clinical diagnosis of Type 1, 2 or 3 spinal muscular atrophy (SMA) or 1–4 SMN2 copies.JEWELFISH (NCT03032172) is an open-label study of risdiplam in patients with SMA who previously received RG7800 (RO6885247), nusinersen (SPINRAZA®), olesoxime or onasemnogene abeparvovec (ZOLGENSMA®).JEWELFISH assesses the safety, tolerability and pharmacokinetic/pharmacodynamic (PD) relationship of risdiplam in a broad range of ages (1–60 years), SMA types (1–3), SMN2 copy numbers (1–4) and motor function (nonsitters, sitters and walkers). We previously presented safety data from 173 patients (data cut-off: 31 July 2020): 13 previously received RG7800, 76 received nusinersen, 70 received olesoxime and 14 received onasemnogene abeparvovec. Risdiplam led to a rapid and sustained >2-fold increase in SMN protein (data cut-off: 1 June 2020), consistent with data from treatment-naïve patients with Types 2/3 SMA (SUNFISH;NCT02908685).No drug-related safety findings leading to withdrawal were reported for any patients in JEWELFISH. The safety profile of risdiplam was consistent with observations in treatment-naïve patients. Here we present 12-month safety, PD and exploratory efficacy data.