SMA is a progressive neuromuscular disease that often presents in infancy or childhood and causes muscle weakness and atrophy. Not only is this disease potentially devastating to the patient, but the condition can also come with substantial economic costs, as well as a hefty burden on patient and caregiver quality of life. With this new approval, risdiplam is now the first oral drug approved for SMA, joining an arsenal that includes a pair of injectable drugs— the first, nusinersen, was originally approved in 2016; the second, onasemnogene abeparvovec (Zolgensma), was approved in 2019.
“The efficacy of [risdiplam] for the treatment of patients with infantile-onset and later-onset SMA was evaluated in two clinical studies,” the FDA explained. “The infantile-onset SMA study included 21 patients who had an average age of 6.7 months when the study began. In that open-label study, efficacy was established based on the ability to sit without support for at least five seconds and survival without permanent ventilation. After 12 months of treatment, 41% of patients were able to sit independently for more than five seconds, a meaningful difference from the natural progression of the disease because almost all untreated infants with infantile-onset SMA cannot sit independently. After 23 or more months of treatment, 81% of patients were alive without permanent ventilation, which is a noticeable improvement from typical disease progression without treatment.
“Patients with later-onset SMA were evaluated in a second randomized, placebo-controlled study,” they continued. “The study included 180 patients with SMA aged two to 25 years. The primary endpoint was the change from baseline in MFM32 (a test of motor function) total score at the one-year mark. Patients on [risdiplam] saw an average 1.36 increase in their score at the one-year mark, compared to a 0.19 decrease in patients on placebo.”
Side effects associated with oral risdiplam included fever, diarrhea, rash, mouth ulcers, arthralgia, and urinary tract infections. The FDA added that, while patients with infantile-onset SMA experienced similar side effects as patients with later-onset SMA, the infantile onset population faced additional side effects, including upper respiratory tract infections, pneumonia, constipation, and vomiting. “Patients should avoid taking [risdiplam] together with drugs that are multidrug and toxin extrusion substrates because [risdiplam] may increase plasma concentrations of these drugs,” the agency warned.
Oral risdiplam is manufactured by Genentech, Inc.
John McKenna, Associate Editor, BreakingMED™
Cat ID: 130
Topic ID: 82,130,730,130,192,725