FDA Accelerated Approval for Duchenne Gene Therapy

FDA has granted Sarepta Therapeutics accelerated approval for its BLA for Elevidys, the first gene therapy to treat pediatric patients aged four through five years of age with Duchenne muscular dystrophy (DMD) with a confirmed mutation in the DMD gene who do not have a pre-existing medical reason preventing treatment with this therapy.

The recombinant gene therapy is designed to “deliver into the body a gene that leads to production of Elevidys micro-dystrophin, a shortened protein (138 kDa, compared to the 427 kDa dystrophin protein of normal muscle cells) that contains selected domains of the dystrophin protein present in normal muscle cells,” an FDA release says.

Approval was based on data from a randomized clinical trial that established that Elevidys increased the expression of the Elevidys micro-dystrophin protein in treated patients, FDA says. This effect “is reasonably likely to predict clinical benefit in individuals four to five years of age with DMD who do not have significant pre-existing antibody titers against the AAV rh74 vector or have other contraindications based on the inclusion criteria of the clinical trials.”

As part of the approval, the agency is requiring Sarepta to complete a clinical study to confirm the biologic’s clinical benefit. “The required study is designed to assess whether Elevidys improves physical function and mobility in ambulatory DMD patients with a confirmed mutation in the DMD gene,” it says.

On the safety side, FDA says the most commonly reported side effects were vomiting, nausea, acute liver injury, pyrexia and thrombocytopenia. “Patients’ liver function should be monitored before treatment with Elevidys, and weekly for the first three months after treatment” it says.

Last week, Public Citizen’s Health Research Group urged FDA to not grant the product an accelerated approval because it says the data do not justify it (see earlier story). In a 6/15 letter to the agency, the advocacy group said the data failed to demonstrate significant muscle-function sparing in the only randomized clinical trial so far. “Moreover, the treatment has safety concerns — most notably that the viral vector needed to deliver this gene therapy cannot be used repeatedly, even for another treatment that might later prove to be safe and effective,” it said.

The group’s letter also said it was concerned about the anecdotal video evidence of patients’ improvements presented in last month’s advisory committee meeting (see earlier story). FDA’s Cellular, Tissue, and Gene Therapies Advisory Committee 5/12 voted 8 to 6 to recommend approval. A briefing document issued in advance of the meeting said agency medical reviewers found that “the clinical studies conducted to date do not provide unambiguous evidence that SRP-9001 is likely beneficial for ambulatory patients with DMD.”