Spinal muscular atrophy (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 a centrally and peripherally distributed oral SMN2 pre mRNA splicing modifier that increases the levels of functional SMN protein. Risdiplam (EVRYSDI™) has been approved by the FDA for the treatment of patients with SMA, aged 2 months and older.
The risdiplam clinical development program consists of four studies in a broad population of individuals with SMA:
•FIREFISH (NCT02913482) is a two-part study assessing the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD) and efficacy in infants with Type 1 SMA (inclusion criteria 1–7 months at enrollment)
•SUNFISH (NCT02908685) is a two-part study assessing the safety, tolerability, PK, PD and efficacy in patients with Type 2 or 3 SMA (inclusion criteria 2–25 years at enrollment)
•JEWELFISH (NCT0302172) assesses the safety, tolerability, PK and PD in patients with SMA (inclusion criteria 6 months–60 years at enrollment) who previously received RG7800 (RO6885247), nusinersen (SPINRAZA®), olesoxime or onasemnogene abeparvovec-xioi (ZOLGENSMA®).
•RAINBOWFISH (NCT03779334) assesses the efficacy, safety, PK and PD in infants (inclusion criteria birth-6 weeks at first dose) with genetically diagnosed and presymptomatic SMA.
To determine the long-term safety profile of risdiplam in individuals with SMA who have participated in the risdiplam clinical development program.
Pooled analyses from FIREFISH Parts 1 and 2, SUNFISH Part 1 and JEWELFISH showed no treatment-related safety findings leading to withdrawal from risdiplam treatment for up to 39 months in 465 patients (data-cut: 15th January 2020). Here we will present updated pooled safety analyses for the risdiplam studies.
This analysis will add to the understanding of the long-term safety profile of risdiplam.