The US 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.

The agency approved Amondys 45 based on an increase in dystrophin production in skeletal muscle observed in patients treated with the therapy. This is reportedly 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, according to the FDA in a news release.

The FDA is granting the approval to Sarepta Therapeutics Inc.

“We celebrate the approval of Amondys 45, which represents the third exon-skipping drug from Sarepta, and the fifth drug approved for Duchenne muscular dystrophy. MDA funded the development of this technology in the laboratory of Dr. Steve Wilton in the 1990’s and it’s very gratifying to see that technology being extended by Sarepta to benefit more and more Duchenne families.”

— Muscular Dystrophy Association Executive Vice President and Chief Research Officer Sharon Hesterlee, PhD, in a separate news release

Study Results

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, the release explains.

Accelerated Approval Pathway

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, per the FDA release.

[Source(s): US Food and Drug Administration, Muscular Dystrophy Association, PR Newswire]

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