Risdiplam Treatment Results in 90% Survival Rate for Infants with Spinal Muscular Atrophy

Data from the pivotal FIREFISH study (NCT02913482) of risdiplam (Evrysdi; Genentech, San Francisco, CA) showed 90% of infants with symptomatic type 1 spinal muscular atrophy (SMA1) survived without permanent ventilation. . Of the participants treated with risdiplam at 12 months, 33% (7/21) were able to sit without support for at least 5 seconds. The study also found that treatment with risdiplam increased the levels of survival of motor neuron (SMN) protein. 

“Since Evrysdi was approved by the Food and Drug Administration (FDA) in August, we have been inspired by the stories and sense of hope that we have heard from people living with SMA and their families about the impact Evrysdi has had in their lives,” said Levi Garraway, MD, PhD, chief medical officer and head of Global Product Development. “The publication of the data in the New England Journal of Medicine reinforces the value of Evrysdi as an important treatment option for SMA.” 

The exploratory efficacy analysis found after 12 months of treatment, 7 of the 21 (33%) infant participants were able to sit without support for at least 5 seconds. Motor milestones were assessed by the Gross Motor Scale of the Bayley Scales of Infant and Toddler Development, All 7 participants who sat up independently had received the high dose, 7 out of 17 (41%), received the lower dose selected for the confirmatory part 2 of the study. Of the participants in the high-dose cohort, 53%, 9 out of 17, had upright head control after 12 months of treatment, and 1 infant (6%; 1/17) was able to stand.

The FIREFISH study is an open-label, 2-part pivotal study, designed to assess risdiplam safety, tolerability, efficacy, pharmacokinetics (PK), and pharmacodynamics (PD) in participants aged 1 to 7 months with SMA1. Part 1 of the study evaluated several doses of risdiplam and determined the therapeutic dose of 0.2 mg/kg for part 2. Among the 21 infants enrolled in part 1 of the FIREFISH study, the median duration of treatment was 14.8 months at the time of analysis. The median age at enrollment was 6.7 months and symptom onset between the ages of 28 days to 3 months.

The most common adverse events were fever (pyrexia; 52%), upper respiratory tract infections (43%), diarrhea (29%), cough (24%), vomiting (24%), constipation (19%) and pneumonia (19%).