Today, the U.S. Food and Drug Administration granted approval for Amondys 45 (casimersen) injection for the treatment of Duchenne muscular dystrophy (DMD) in patients who have a confirmed mutation of the DMD gene that is amenable to exon 45 skipping (Exons are pieces of DNA that provide information for making proteins in a person’s genome). The agency approved Amondys 45 based on an increase in dystrophin (a protein that helps keep muscle cells intact) production in skeletal muscle observed in patients treated with the therapy. This is the first FDA-approved targeted treatment for patients with this type of mutation. Approximately 8% of patients with DMD have a mutation that is amenable to exon 45 skipping.

“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 the 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.”

DMD is a rare genetic disorder characterized by progressive muscle deterioration and weakness. It is the most common type of muscular dystrophy. DMD is caused by mutations in the DMD gene that results in an absence of dystrophin, a protein found in muscle fiber. The first symptoms are usually seen between three and five years of age and worsen over time. DMD occurs in approximately one out of every 3,600 male infants worldwide; in rare cases, it can affect females.

Amondys 45 was evaluated in a double-blind, placebo-controlled study in which 43 patients were randomized 2:1 to receive either intravenous Amondys 45 (30 mg/kg) or placebo. All patients were male, between 7 and 20 years of age, and had a genetically confirmed mutation of the DMD gene that is amenable to exon 45 skipping.

In the study, patients who received Amondys 45 showed a significantly greater increase in dystrophin protein levels from baseline to week 48 of treatment compared to those who received placebo.

The FDA 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 side effects observed in DMD patients treated with Amondys 45 were upper respiratory tract infections, cough, fever, headache, joint pain and throat pain.

Although kidney toxicity was not observed in the Amondys 45 clinical studies, kidney toxicity was observed in the nonclinical studies. Kidney toxicity, including potentially fatal glomerulonephritis, has been observed after administration of some antisense oligonucleotides. Kidney function should be monitored in patients taking Amondys 45.

Amondys 45 was approved using the Accelerated Approval pathway, under which the FDA may approve drugs for serious conditions where there is unmet medical need and a drug is shown to have certain effects that are reasonably likely to predict a clinical benefit to patients. Further study is required to verify and describe anticipated clinical benefits of Amondys 45, and the sponsor is currently conducting an ongoing, double-blind, placebo-controlled, multicenter study designed to evaluate the safety and efficacy of Amondys 45 in ambulatory DMD patients.

The FDA granted this application Fast Track and Priority Review designations. Amondys 45 also received Orphan Drug designation, which provides incentives to assist and encourage the development of drugs for rare diseases.

The FDA is granting the approval to Sarepta Therapeutics, Inc.

The FDA, an agency within the U.S. Department of Health and Human Services, protects the public health by assuring the safety, effectiveness, and security of human and veterinary drugs, vaccines and other biological products for human use, and medical devices. The agency also is responsible for the safety and security of our nation’s food supply, cosmetics, dietary supplements, products that give off electronic radiation, and for regulating tobacco products.