In the 2-year pivotal FIREFISH study (NCT02913482) of risdiplam (Evrysdi; Genentech, San Francisco, CA), infants with symptomatic type 1 spinal muscular atrophy (SMA) who were treated with risdiplam at age 2 to 7 months continued to improve and achieve motor milestones.
Of the 21 participants who were enrolled in the trial initially, 88% had a therapeutic dose and required no permanent ventilation at 2 years. At the 2-year timepoint, 59% of infants were able to sit without support for at least 5 seconds. Comparing progress at 2 years vs 1 year, an additional 2 children had head control (11/17 at 2 years vs 9/17 at 1 year), 3 more could turn themselves over (5/17 at 2 years vs 2/17 at 1 year), and 4 more were able to stand with support(5/17 at 2 years vs 1/17 at 1 year), some of whom stood independently. After 2 years of treatment with risdiplam, 2 more children attained a CHOP-INTEND score of 40 points or more (12/17 at 2 years vs 10/17 at 1 year). All participants had increased scores from the end of the first year to the end of the second year. Of the 14 children alive after 2 years, 100% maintained the ability to swallow and 93% were able to eat.
Of the 17 infants treated with the therapeutic dose, 2 experienced fatal complications of SMA at 8 months and 13 months of treatment and 1 infant was withdrawn from the study and died 3.5 months later. However, these experiences were not related to the risdiplam treatment.
The FIREFISH study is an open-label 2-part pivotal clinical trial in infants with type 1 SMA. The first part was a dose-escalation study in 21 infants, assessing the safety profile of risdiplam. The second part is a pivotal, single-arm study of risdiplam in 41 infants with type 1 SMA treated for 2 years. The second part assessed efficacy as measured by the proportion of infants sitting without support after 12 months of treatment, as assessed in the BSID-3.
The most common adverse events (n=21) included fever (71%), upper respiratory tract infection (52%), cough (33%), vomiting (33%), diarrhea (29%), and respiratory tract infection (29%). The most serious adverse event that occurred in 24% of infants was pneumonia.
Chen Zhao, MD; Jonathan G. Hakun, PhD; Krishnankutty Sathian, MBBS, PhD; and Nikolaos Scarmeas, MD, MS, PhD
Tzu-Ying Chuang, MD, PhD, and Dhanashri Miskin, MD