Pooled Safety Data from the Risdiplam Clinical Trial Development Program

Risdiplam is a centrally and peripherally distributed oral survival of motor neuron 2 (SMN2) pre mRNA splicing modifier that increases the levels of functional SMN protein. Risdiplam (EVRYSDI™) has been approved by the US Food and Drug Administration for the treatment of patients with spinal muscular atrophy (SMA), aged 2 months and older. The risdiplam clinical development programme consists of four studies in a broad population of individuals with SMA. FIREFISH ( NCT02913482 ) and SUNFISH ( NCT02908685 ) are two-part studies assessing safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD) and efficacy in infants with Type 1 SMA and patients with Type 2/3 SMA, respectively. JEWELFISH (NCT0302172) assesses safety, tolerability, PK and PD in patients with SMA who previously received RG7800 (R06885247), nusinersen (SPINRAZA®), olesoxime or onasemno- gene abeparvovec-xioi (ZOLGENSMA®). RAINBOWFISH ( NCT03779334 ) assesses efficacy, safety, PK and PD in infants with genetically diagnosed and presymptomatic SMA. Pooled analyses of FIREFISH and SUNFISH Parts 1 and 2 and JEWELFISH were conducted to determine the long-term safety profile of risdiplam. At the data-cut (15th January 2020) no treatment-related safety findings led to withdrawal from up to 39 months’ risdiplam treatment in 465 patients. Here we will present updated pooled safety analyses for the risdiplam studies. g.baranello@ucl.ac.uk