It is unclear if the first gene therapy for Duchenne muscular dystrophy will be approved by the Food and Drug Administration (FDA), as scientists examining the treatment remain skeptical of its effectiveness days before a major regulatory conference.
The FDA is holding a panel discussion to determine whether or not Duchenne patients who are still able to walk should be allowed to take the therapy, which was created by biotechnology company Sarepta Therapeutics. Experts will be asked to decide if the therapy’s capacity to boost production of a potentially beneficial protein called microdystrophin warrants an accelerated approval.
The agency will additionally request that the panel talk about the effect the authorization would have on a Phase 3 trial of the treatment, but they will not be voting on it. Results from that research, which will provide a more comprehensive test of the treatment’s impact and could influence the FDA’s decision, are expected from Sarepta in roughly six months.
Although the FDA usually takes the recommendations of its advisory committees into consideration, this is not always the case. The deadline for the agency’s decision is May 29.
Wednesday’s documents highlight the FDA scientists’ viewpoint and provide a glimpse into their perspective on the information Sarepta has gathered thus far. They demonstrate that the agency’s employees do not think Sarepta has produced “unambiguous evidence” that its treatment can benefit people with Duchenne.
“It is challenging to conclude with reasonable certainty from the data provided by the applicant either that [the therapy] is likely effective for younger patients, or that it is likely ineffective for older patients or those with somewhat poorer functional status,” FDA staff stated.
They were worried about greenlighting an ineffective gene treatment. Patients are often only given one shot at receiving a therapy like Sarepta’s since the medicine causes an immune response to the modified virus that administers it.
While the virus used by Sarepta is not believed to be harmful, it has been linked to major side effects in clinical trials of gene treatments. In examinations using Sarepta, the most commonly reported adverse events were sickness, vomiting, and liver damage. Five cases of severe acute liver damage, one incidence of muscular weakness, and a form of cardiac inflammation were also noted by FDA reviewers during clinical testing. Sarepta ruled out individuals with certain genetic variants from testing because of the risk of myositis, a kind of muscular weakness that is known to be a common side effect of microdystrophin gene treatments.
Duchenne is a rare, expanding, and deadly disorder caused by a genetic defect that prevents the body from making dystrophin, a protein that normally protects muscles. Muscle weakness and atrophy characterize this condition, which affects boys almost exclusively. Patients often lose their mobility in their teens and pass away from cardiovascular or respiratory failure by the time they are 30.
Several medications, including three from Sarepta, known as “exon skippers,” are suspected – but have not been shown – to moderately delay the progression of the disease by producing a shorter version of dystrophin. Steroids are used by most patients; however, they have negative side effects and can hinder a child’s growth.
The goal of Sarepta’s gene therapy is to provide long-term, perhaps permanent, recovery after a single treatment. It stimulates the production of microdystrophin, a smaller form of the protein that is deficient in people with Duchenne muscular dystrophy.