- In documents released on Thursday, the FDA criticized Sarepta’s Duchenne muscular dystrophy (DMD) drug eteplirsen, expressing concern about the small trial size and the drug’s effect on dystrophin – the main therapeutic target of the treatment.
- The FDA posted the documents ahead of an advisory committee meeting on the drug next Monday, April 25. The panel had been rescheduled from an original date of January 21 due to bad weather.
- After the meeting was rescheduled, Sarepta submitted new data on eteplirsen and responded to the FDA’s initial staff review in January. However, these new documents suggest the FDA’s position remains critical.
- The level of political pressure the FDA faces on this particular drug has intensified, as patient groups continue to push for accelerated approval of eteplirsen. Within the last two months a group of 109 lawmakers from Congress and a group of roughly three dozen medical experts each sent a letter to the FDA advocating for the drug’s approval.
DMD is a rare genetic disease, which mainly affects young men. In those affected by the disease with the disease, the body does not produce dystrophin, which is necessary for the integrity of muscle fibers. Without it, muscles degenerate and patients gradually lose mobility. Most patients die before age 30.
Roughly 13,000 boys have DMD, though there are a small number of girls who also have this disease.
Eteplirsen is intended to treat boys with a specific type of DMD affecting about 13% of the total patient population. In this cohort, eteplirsen has been shown to increase the level of the target protein dystrophin.
The FDA's primary problem with eteplirsen is the size of the drug’s trial. Only 12 boys are in the trial and all are being treated with active drug. In addition, the agency has also expressed concerns about whether the main endpoints—a 6-minute walk distance (6MWD) test and biomarker outcomes—are sufficient and clinically appropriate.
Political pressure has grown, with highly influential lawmakers and medical experts leaning heavily on the FDA to approve eteplirsen now, and allow Sarepta to continue conducting confirmatory trials post-approval.
But the FDA has encouraged the use of a placebo-controlled, blinded trial for the drug, and appears skeptical of the historical control used by Sarepta, reports The Street.
However, for those affected by DMD, including parents of children with DMD, the idea of conducting such a trial is fraught with ethical challenges.
Monday’s panel meeting will highlight the challenging intersections between patient advocacy and rigorous standards for drug trials and approval. A negative review by the advisory committee would lengthen the odds of the FDA approving eteplirsen.