Evrysdi improves, sustains motor function in spinal muscular atrophy

Evrysdi, a survival motor neuron 2-directed RNA splicing modifier, both sustained and improved motor function at 24 months in children and adults with type 2 or type 3 spinal muscular atrophy, according to results from the SUNFISH trial.

Patients and caregivers reported improvements in functional independence and the ability to perform daily tasks, according to a press release on the trial results.

The second part of the SUNFISH trial — a double-blind, placebo-controlled study — examined motor function in 180 participants aged 2 to 25 years with type 2 or type 3 spinal muscular atrophy (SMA). The researchers examined the total score on Motor Function Measure 32 (MFM-32), a scale used to analyze fine and gross motor function in individuals with neurological disorders such as SMA, at 12 months, as well as other markers.

Two-year efficacy and safety data demonstrated “improvement or maintenance of motor function” in the second year of treatment with Evrysdi (risdiplam, Genentech) according to the MFM-32, the Revised Upper Limb Module (RULM) and the Hammersmith Functional Motor Scale Expanded (HFMSE). Study results demonstrated maintenance of improvements in motor function between 12 and 24 months according to the MFM-32; improved motor function as measured by the RULM and HFMSE between 12 and 24 months; and stabilized motor function according to the MFM-32, RULM and HFMSE among patients who started treatment with risdiplam following 12 months on placebo. The researchers also observed an increased total score from baseline on the caregiver-reported SMA Independence Scale (SMAIS) upper limb module and a stabilization of the patient-reported SMAIS score between months 12 and 24.

The researchers reported reductions in serious adverse events, high-grade adverse events and treatment-related adverse events in the second year vs. the first year in both treatment arms, according to the press release. The most frequent adverse events in the risdiplam arm and the placebo/risdiplam arm from 12 to 24 months included upper respiratory tract infection (15.8% and 10%, respectively), nasopharyngitis (21.7% and 16.7%, respectively), pyrexia (13.3% and 10%, respectively), headache (10% and 16.7%, respectively), diarrhea (7.5% and 10%, respectively), vomiting (11.7% and 13.3%, respectively) and cough (10% and 8.3%, respectively). The most frequent serious adverse events included pneumonia (6.7% and 0%, respectively) and influenza (0.8% and 0%, respectively).

Risdiplam treats SMA caused by mutations in chromosome 5q that result in survival motor neuron protein deficiency by increasing and sustaining production of that protein, according to the press release. The drug distributes evenly throughout the body, including the central nervous system, and is given daily in liquid form, either by mouth or feeding tube. The FDA approved risdiplam as the first oral agent for SMA in August 2020.

Roche leads the development of risdiplam in the United States in collaboration with the SMA Foundation and PTC Therapeutics; it is marketed in the United States by Genentech, a member of the Roche Group.

“These data further support the strong U.S. launch and the need for an at home oral treatment option for the SMA community,” Stuart W. Peltz, PhD, chief executive officer of PTC Therapeutics, said in the release.