Sma - treatment

Type 1 SMA is a rare, severe neuromuscular disease in which untreated infants fail to achieve major motor milestones and typically die or require permanent ventilation before 2 years of age. Risdiplam (EVRYSDI™) is a centrally and peripherally distributed, oral SMN2 pre-mRNA splicing modifier that has been approved by the FDA for the treatment of patients with SMA, aged 2 months and older. FIREFISH (NCT02913482) is a multicenter, open-label, two-part study of risdiplam in infants with Type 1 SMA and two SMN2 gene copies (inclusion criteria 1–7 months old at enrollment). FIREFISH Part 1 assesses safety, tolerability and pharmacokinetics/ pharmacodynamics of different risdiplam doses (low-dose cohort, n=4; high-dose cohort, n=17). Pivotal Part 2 (N=41) assesses efficacy and safety of risdiplam at the dose selected from Part 1. The primary endpoint of Part 2 at Month 12 was met: 29% (12/41) of infants were able to sit without support for ≥5 seconds, as measured by the gross motor scale of the Bayley scales of infant and toddler development, third edition (item 22; P<0.0001, performance criterion=5%). Previously we presented pooled safety and efficacy data from 58 infants in FIREFISH Part 1 (high-dose cohort, n=17) and Part 2 (N=41) who had received treatment with risdiplam for ≥12 months. At Month 12, there were no treatment-related adverse events leading to withdrawal and 88% (51/58) of infants were alive and did not require permanent ventilation. Infants showed improvement in motor function and achieved motor milestones that are not observed in the natural history of Type 1 SMA. Here, we present pooled safety and efficacy data from 58 infants in FIREFISH Part 1 (high-dose cohort, n=17) and Part 2 (N=41) who received risdiplam treatment for ≥24 months. The safety and efficacy of risdiplam are consistent between FIREFISH Parts 1 and 2. Both are ongoing globally and will provide further data on the long-term efficacy and safety of risdiplam in infants with Type 1 SMA.