At the 1-year point of the Firefish part 2 (NCT02913482), a pivotal global study evaluating risdiplam (Genentech, San Francisco, CA), 29% (12/41; P<.0001) of infants with spinal muscular atrophy type 1 (SMA1) who were treated at age 1 to 7 months sat independently. This milestone is never achieved in infants with SMA1 who are not treated. In addition, 18 (43.9%) infants were able to hold their head upright, 13 (31.7%) were able to roll to the side and 2 (4.9%) infants were able to stand with support, as measured by the Hammersmith Infant Neurological Examination 2 (HINE-2).
“These results confirm the clinically meaningful efficacy of risdiplam in infants with an advanced and difficult-to-treat disease,” said Levi Garraway, MD, PhD, chief medical officer and head of Global Product Development. “We thank the SMA community for their partnership and especially the 62 families from around the world who participated in parts 1 and 2 of the Firefish study.”
At the time of analysis, the median duration of treatment was 15.2 months and the median age was 20.7 months. Of those treated, 93% (38/41) were alive and 85.4% (35/41) were event-free; without treatment, infants with SMA1 typically are not alive or are on permanent ventilation at this age. In the study, 3 infants experienced fatal complications of their disease within the first 3 months of treatment. None of theose complications were considered treatment related. Of those treated, 90% (37/41) had a Children’s Hospital of Philadelphia infant test of neuromuscular disorders (CHOP-INTEND) score increase of at least 4 points, with 56% (23/41) achieving a score above 40; the median increase was 20 points.
In an exploratory endpoint, 95% of infants who were alive at 12 months (36/38) maintained the ability to swallow and 89% (34/38) were able to feed orally. In contrast, in a natural history cohort, all infants with type 1 SMA older than 12 months required feeding support.
“These results are particularly encouraging given the median age at enrollment was 5.3 months, so these infants already had progressed disease,” said professor Laurent Servais, FIREFISH investigator and professor of Paediatric Neuromuscular Diseases at the MDUK Oxford Neuromuscular Centre. “Maintaining the ability to swallow is particularly important as it helps infants to feed and suggests risdiplam has a major effect on bulbar function.”
Safety for risdiplam in the Firefish study was consistent with its previously reported safety profile and no new safety signals were identified. The most common adverse events (AE) were upper respiratory tract infection (46.3%), pneumonia (39%), pyrexia (39%), constipation (19.5%), nasopharyngitis (12.2%), rhinitis (12.2%) and diarrhea (9.8%). The most common serious adverse events were pneumonia (31.7%), bronchiolitis (4.9%), respiratory failure (4.9%), and hypotonia (4.9%).
Erin Furr Stimming, MD, and Jorge Patiño, MD
Stefan Nicolau, MD, and Elie Naddaf, MD
Rachana Gandhi Mehta, MD; Vanessa Baute Penry, MD; and Herbert Lloyd Bonkovsky, MD