Treatments with risdiplam (Genentech, San Francisco, CA) improved motor function in the Sunfish study (NCT02908685). Change from baseline on the motor function measure 32 scale (MFM-32) was significantly greater in individuals treated with risdiplam compared with placebo (1.55 point mean difference; P=.0156). The revised upper limb module (RULM), a key secondary endpoint, also showed an improvement (1.59 point difference; P=.0028). Safety for risdiplam in the study was consistent with its known safety profile. This data was presented at the 2nd International Scientific and Clinical Congress on spinal muscular atrophy (SMA) from February 5th to the 7th in Evry, France.
Exploratory subgroup analyses showed that the strongest responses in MFM-32 with risdiplam vs placebo were observed in the youngest age group (2-5 years) (78.1% vs 52.9% achieving ≥3 point increase). The stabilization of SMA was observed in the 18 to 25 years age group (57.1% vs 37.5%, with stabilization defined as a ≥0 point increase), which is the goal of treatment for those with more established disease.
The most common adverse events were upper respiratory tract infection (31.7%), nasopharyngitis (25.8%), pyrexia (20.8%), headache (20%), diarrhea (16.7%), vomiting (14.2%), and cough (14.2%). Although the rate of lower respiratory tract infections overall was similar in both treatment arms (risdiplam 19%, placebo 20%), serious lower respiratory tract infections occurred in more individuals in the risdiplam group (risdiplam 10%, placebo 2%) but were reported as unrelated and resolved without change to study treatment. To date, more than 400 individuals have been treated with risdiplam across all studies, with no treatment-related safety findings leading to study withdrawal in any risdiplam trial.
“Risdiplam is the first potential treatment to have pivotal placebo-controlled data in a broad population of patients, including children, teenagers, and adults,” said Sunfish principal investigator Eugenio Mercuri, MD, PhD, Department of Pediatric Neurology, Catholic University, Rome, Italy. “The data suggest that risdiplam can preserve and potentially enable greater independence through improved motor function in people with type 2 or nonambulant type 3 SMA.”
Duriel I. Hardy, MD, and Sona Narula, MD
Lawrence W. Brown, MD