FDA Approves Polarizing First Drug for Duchenne Muscular Dystrophy

On Monday morning the Food and Drug Administration approved a controversial drug, eteplirsen, manufactured by Sarepta that is meant to help mainly young boys (X-linked disorder so females are rarely affected) fight Duchenne muscular dystrophy (DMD), a disease that causes muscle degeneration and premature death.

Boys with DMD made statements a few months ago about the benefits they experienced from using eteplirsen.

The controversy over the drug stems from the lack of clinical trials by Sarepta Therapeutics proving the efficacy and safety of the drug, eteplirsen. The study supporting approval was a small trial with just 12 boys who carry a gene mutation that occurs in 13% of the 9,000 to 12,000 boys in the U.S. with DMD. The FDA granted the drug an accelerated approval, taking into account the emotional and passionate testimonies from the patients’ parents that the drug was truly helping their sons. As a condition of the approval, Sarepta will have to conduct a 2 year, randomized controlled trial to verify the “clinical benefit” of the drug. The purpose is to determine whether the drug actually improves motor functions. If the trial fails, the FDA could move to withdraw approval.

Rare diseases are difficult cases for the FDA. Rare diseases inherently means that there are few people with the disease, which means a smaller sample size to test the efficacy of a drug. Even if the drug was shown to improve the lives of patients, there are side effects that only become known after several years of using the drug which could, in some cases, be more detrimental than the disease itself. Additionally, the small population of people with the disease also results in scientists knowing less about how the disease affects the body.

DMD is a debilitating disease that affects 1 in 3,600 boys. The disease is caused by a mutation in the gene dystrophin resulting in faulty dystrophin proteins. This ultimately causes muscle fibers to degenerate, making voluntary movements almost impossible as the disease progresses. The average life expectancy for individuals afflicted with DMD is around 25, when the disease ultimately causes difficulty in breathing and additional heart problems.

So how does this drug work? Eteplirsen is an “exon-skipping” drug. As stated earlier, Duchenne muscular dystrophy is caused when a mutation in the DMD gene changes the DMD RNA so that it no longer codes for functional dystrophin protein. This is usually due to a mutation that alters the reading frame of the RNA downstream of the mutation. Eteplirsen triggers excision of exon 51 during pre-mRNA splicing of the dystrophin RNA transcript. Skipping exon 51 changes the downstream reading frame of dystrophin; giving eteplirsen to a healthy person would result in production of dystrophin mRNA which would not code for functional dystrophin protein but, for DMD patients with particular frameshifting mutations, giving eteplirsen can restore the reading frame of the dystrophin mRNA and result in production of functional dystrophin.

Proponents of the drug say that it has immensely helped their sons partially regain their ability to walk. The families affected by Duchenne muscular dystrophy are one of the most vocal and involved patient communities since the days when HIV patients pushed the agency to approve more drugs.

This unexpected approval by the FDA gives hope to other other patients suffering from a variety of rare diseases. These patients are often stuck in a limbo where drugs that may help them are caught up in clinical trials.

An outspoken advocate of eteplirsen, Terri Ellsworth has a 15 year old son with DMD who was one of the dozen boys in the trial.

Stay tuned for more news about this controversial approval, and how it may affect future drug approvals!


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