To assess the safety, tolerability and pharmacokinetic/pharmacodynamic (PK/PD) relationship of risdiplam (RG7916) in non-naïve patients with spinal muscular atrophy (SMA) who have been treated with risdiplam in the ongoing JEWELFISH study.

SMA is a severe, progressive neuromuscular disease caused by reduced levels of survival of motor neuron (SMN) protein due to deletions and/or mutations of the SMN1 gene. A second SMN gene, SMN2, produces only low levels of functional SMN protein. Risdiplam is an orally administered, centrally and peripherally distributed SMN2 pre-mRNA splicing modifier that increases the levels of functional SMN protein.

JEWELFISH (NCT03032172) is an ongoing, multicenter, open-label study evaluating the safety, tolerability and PK/PD relationship of daily oral risdiplam in non-naïve patients with SMA, aged 6 months to 60 years. JEWELFISH participants previously received RG7800 (RO6885247), nusinersen (SPINRAZA®), olesoxime or onasemnogene abeparvovec-xioi (ZOLGENSMA®).

We present safety data from 45 patients with SMA (data-cut: 28^th June 2019) who received risdiplam for up to 28.9 months (nine patients previously received RG7800, 24 patients received nusinersen and 12 patients received olesoxime). No drug-related safety findings leading to withdrawal were reported. In an earlier analysis of SMN protein in whole blood, while patient numbers were limited (n=18), the magnitude of SMN protein increase (>2-fold) was comparable to that in SUNFISH Part 1 (NCT02908685) in patients with Type 2 and 3 SMA who had not previously received an SMN2-targeting therapy.