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 gene, SMN2, produces only low levels of functional SMN protein. 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). Part 1 assesses the safety, tolerability and pharmacokinetics/pharmacodynamics of risdiplam dose levels (low-dose cohort, n=4; high-dose cohort, n=17). The pivotal Part 2 (N=41) assesses the efficacy and safety of risdiplam at the dose selected from Part 1.
To determine the efficacy and safety of risdiplam in infants with Type 1 SMA treated for 24 months during Parts 1 and 2 of the FIREFISH study.
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 risdiplam treatment for ?12 months (data-cut: 14 November 2019). At Month 12, 88% (51/58) of infants were alive and did not require permanent ventilation and 57% (33/58) scored ?40 on the Children’s Hospital of Philadelphia Infant Test of Neuromuscular Disorders, showing improvements in motor function. Infants also achieved motor milestones, including sitting without support, standing with support and bouncing (assessed by the Hammersmith Infant Neurological Examination, Module 2), that are not observed in the natural history of Type 1 SMA. There were no treatment-related adverse events leading to withdrawal after 12 months of treatment.
Pooled FIREFISH safety and efficacy data will be presented for 58 infants who received risdiplam for ?24 months.
The safety and efficacy of risdiplam are consistent between FIREFISH Parts 1 and 2. Both Parts 1 and 2 are ongoing globally and will provide further data on the long-term efficacy and safety of risdiplam in infants with Type 1 SMA.