Once-daily Therapy Improves Motor Function in Types 2 and 3 Spinal Muscular Atrophy

In patients with type 2 or nonambulant type 3 spinal muscular atrophy, a year of once-daily risdiplam significantly improved motor function compared with placebo, according to study published in The Lancet Neurology.

“Risdiplam is an oral small molecule approved for the treatment of patients with spinal muscular atrophy, with approval for use in patients with type 2 and type 3 spinal muscular atrophy granted on the basis of unpublished data,” an international team of researchers wrote in the study, which was funded by drugmaker F Hoffmann-La Roche. “The drug modifies pre-mRNA splicing of the SMN2 gene to increase production of functional SMN [survival motor neuron protein].”

The phase 3, double-blind trial randomly assigned patients ages 2 through 25 years with type 2 or nonambulant type 3 spinal muscular atrophy to treatment with either daily oral risdiplam or placebo.

Among 115 patients who received risdiplam and 59 patients who received placebo, the least squares mean change in 32-item Motor Function Measure total score at 12 months was 1.55 higher with risdiplam: 1.36 in the risdiplam group compared with -0.19 in the placebo group.

“Our exploratory subgroup analyses showed that motor function was generally improved in younger individuals and stabilized in older individuals,” researchers wrote, “which requires confirmation in further studies.”

Safety data for 120 patients who received risdiplam and 60 patients who received placebo found pyrexia, diarrhea, rash, mouth and aphthous ulcers, urinary tract infection, and arthralgias occurred more often with risdiplam. Incidence of serious adverse events was similar between the risdiplam and placebo groups with the exception of pneumonia, which occurred in nine patients treated with risdiplam and one patient treated with placebo.

The trial is ongoing, researchers added, to collect additional long-term efficacy and safety evidence in the patient population.

Reference:
Mercuri E, Deconinck N, Mazzone ES, et al. Safety and efficacy of once-daily risdiplam in type 2 and non-ambulant type 3 spinal muscular atrophy (SUNFISH part 2): a phase 3, double-blind, randomised, placebo-controlled trial. Lancet Neurol. 2022;21(1):42-52. doi:10.1016/S1474-4422(21)00367-7