To determine the efficacy and safety of risdiplam in infants with Type 1 SMA after 36 months of treatment.

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 90 countries worldwide.

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 assessed the safety, tolerability and pharmacokinetics/pharmacodynamics of different risdiplam doses. Pivotal Part 2 assessed the safety and efficacy of risdiplam over 24 months at the dose selected from Part 1. Thereafter, infants entered a 3-year open-label extension phase and continue to receive risdiplam at the pivotal dose.

Pooled safety and efficacy data were available from 58 enrolled infants who received risdiplam treatment (Part 1 high-dose cohort, n=17; and Part 2, N=41). As of the cut-off date (23 November 2021), there were no treatment-related adverse events leading to withdrawal, no additional deaths since the clinical cut-off date of the primary analysis (14 November 2019), and no additional infants meeting the definition of permanent ventilation since Month 24. At Month 36, 84% of infants were alive and did not require permanent ventilation. In FIREFISH, infants have achieved motor milestones not observed in the natural history of Type 1 SMA. Overall, infants have maintained or improved their motor skills in terms of developmental milestones and motor function between Month 24 and Month 36.

FIREFISH Parts 1 and 2 are ongoing globally and will provide further safety and efficacy data of risdiplam in Type 1 SMA.