P.113 Safety update: Risdiplam clinical trial development program

Abstract

Risdiplam (EVRYSDI®) is a centrally and peripherally distributed, oral survival of motor neuron 2 (SMN2) pre-mRNA splicing modifier that has been approved in more than 70 countries worldwide. Safety data were analyzed from four studies within the risdiplam clinical development trial program: FIREFISH (NCT02913482) assesses efficacy, safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of risdiplam in infants with type 1 SMA (aged 1–7 months at enrollment). SUNFISH (NCT02908685) assesses efficacy, safety, tolerability, PK and PD of risdiplam in patients with types 2/3 SMA (aged 2–25 years at enrollment). JEWELFISH (NCT03032172) assesses safety, tolerability, PK and PD of risdiplam in patients with SMA (aged 6 months–60 years at enrollment) who previously received RG7800 (RO6885247), nusinersen (SPINRAZA®), olesoxime or onasemnogene abeparvovec (ZOLGENSMA®). RAINBOWFISH (NCT03779334) assesses efficacy, safety, PK and PD of risdiplam in infants (from birth–6 weeks of age at first dose) with genetically diagnosed and presymptomatic SMA. We have previously reported pooled safety analyses from FIREFISH, SUNFISH and JEWELFISH showing no treatment-related safety findings leading to withdrawal in 465 patients treated with risdiplam for up to 46.9 months (data-cuts: 12 November 2020, 30 September 2020 and 29 January 2021, respectively). The rate of adverse events (AEs) per 100 patient years was comparable across the type 1 and type 2/3 SMA populations. The overall rate of serious AEs was higher in the type 1 SMA population compared with the types 2/3 SMA population. With continued risdiplam treatment, there was a marked decline in SAE rates over time in type 1 SMA. Here we will present updated safety analyses from the risdiplam studies, including safety data from the RAINBOWFISH study. Safety data from across the risdiplam studies will add to the understanding of the long-term safety profile of risdiplam.