FDA approves targeted treatment for rare DMD mutation

FDA approved on Thursday casimersen (Amondys 45—Sarepta Therapeutics) injection for the treatment of Duchenne muscular dystrophy (DMD) in individuals with a confirmed mutation of the DMD that is amenable to exon 45 skipping. The drug was approved based on an increase in dystrophin production in skeletal muscle. “Developing drugs designed for patients with specific mutations is a critical part of personalized medicine,” said Eric Bastings, MD, deputy director of the Office of Neuroscience in FDA’s Center for Drug Evaluation and Research. “Today’s approval of Amondys 45 provides a targeted treatment option for Duchenne muscular dystrophy patients with this confirmed mutation.” Casimersen was evaluated in a double-blind, placebo-controlled study involving 43 patients who were randomized to receive either I.V. casimersen (30 mg/kg) or placebo. Study participants who received the drug showed a significantly higher increase in dystrophin protein levels from baseline to week 48 of treatment, compared with placebo recipients. FDA said it “has concluded that the data submitted by the applicant demonstrated an increase in dystrophin production that is reasonably likely to predict clinical benefit in patients with DMD who have a confirmed mutation of the dystrophin gene amenable to exon 45 skipping. A clinical benefit of the drug, including improved motor function, has not been established. In making this decision, the FDA considered the potential risks associated with the drug, the life-threatening and debilitating nature of the disease, and the lack of available therapy.” The most common adverse effects in DMD patients who received casimersen were upper respiratory tract infections, cough, fever, headache, joint pain and throat pain. Kidney toxicity was not seen in the clinical studies, but it was noted in the nonclinical studies. Casimersen was approved under the Accelerated Approval pathway.