FDA Approval Was Granted For a Duchenne Muscular Dystrophy Drug Amid Internal Disagreements


The accelerated approval granted by the FDA for the Duchenne muscular dystrophy drug eteplirsen, developed by Sarepta Therapeutics, was granted only after internal disagreements and protests had been resolved.

According to a recent article published in Biospace, the FDA panel that was convened to decide whether to approve the drug was attended by many parents who expressed their belief, often emotionally, that the drug benefited their children.

In April of this year, an FDA advisory committee expressed their view that the agency did not have sufficient data to grant approval. This objection was accompanied by a second objection that the decision would be made based on one small study involving only twelve patients. Agency staffers and doctors who opposed approval (and still do) made it clear that they considered the evidence severely limited.

Nonetheless, Dr. Janet Woodcock, who is the director of the FDA Center for Drug Evaluation and Research, approved eteplirsen. A protest objecting to Dr. Woodcock’s decision reached the desk of the Commissioner who later deferred to Dr. Woodcock and the drug was approved.

The approval did not sit well with the chief scientist and chairman of one of the FDA committees charged with resolving internal disputes. This scientist said that the data and available information does not support the approval of eteplirsen.

The other opposition came from the director of the Public Citizen Health Research Group who noted the objections voiced by FDA experts after reviewing the drug. He stated that the approval creates a disturbing lack of regard for the legal standards set by the FDA for approving new drugs.

The director stated that the FDA has a long-standing rule that before a drug can be marketed, the drug must show substantial proof of its efficacy. This applies even to drugs for rare diseases.

On The Other Hand . . .

The president of the Muscular Dystrophy Association said that this is what they had dreamed of twenty-five year ago when it first began investing in the research that led to the development of the drug.

About DMD

DMD is a crippling, progressive illness affecting male children. The estimated number of cases worldwide is about 1 in 3500 boys, who may survive to their thirties. Its severe complications are generally respiratory and heart-related. It is a muscle-wasting disorder that is the result of mutations in the dystrophin gene.

The DMD gene is the largest human gene. It provides the instructions for creating dystrophin protein. Dystrophin is found in proteins that strengthen and protect muscle fibers as they contract and relax. A sufficient amount is not produced in DMD patients.

It is the enormous size of the DMD gene that has hampered researchers for years. The DMD gene simply cannot fit into the tools (called viral vectors) that biologists use to transport a genetic substance into the cells, making gene therapies extremely difficult to develop.

Sarepta uses RNA splicing to force cells to “skip” the faulty part of the genetic code. The protein is truncated (shortened) as a result, but is still functional.

If CRISPR is Successful, The Objections to Eteplirsen Would be Mute

CRISPR gene editing has recently been used by researchers at the University of Missouri-Columbia in mouse models. The CRISPR approach edits the gene mutation and transplants muscle that is treated with AAV9 into the mice. The muscle cells that were transplanted will produce the missing supply of dystrophin.

It is noteworthy that an AAV9 style gene therapy was recently FDA approved for the treatment of spinal muscular atrophy.

Research has now shown that CRISPR can edit out the mutation in the animal models that cause the death of muscle cells.

As in all new research, there are issues. In this case, the concern is one of relapse, as the gene-edited muscle cells are known to eventually wear out. The goal then is to correct the muscle stem cell mutation.

If scientists are able to make those corrections, then the regenerated cells taken from the edited stem cells will not harbor the mutation.

Treating the muscle stem cells only one time with CRISPR translates into an increase of dystrophin in regenerated muscle cells. The muscle stem cells were tested to see if CRISPR could edit the DMD mice and the answer was a resounding “yes.”

The scientists believe that CRISPR gene editing will end the search for the treatment of DMD and will produce gene-editing cells throughout the patient’s lifetime.

 Do you know of any children suffering from DMD?


Rose Duesterwald

Rose Duesterwald

Rose became acquainted with Patient Worthy after her husband was diagnosed with Acute Myeloid Leukemia four years ago. He was treated with a methylating agent While he was being treated with a hypomethylating agent, Rose researched investigational drugs being developed to treat relapsed/refractory AML.

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