October 20, 2016
By Mark Terry, BioSpace.com Breaking News Staff
Perhaps it should be no surprise that the U.S. Food and Drug Administration (FDA)’s controversial approval of Sarepta Therapeutics ’s eteplirsen for Duchenne Muscular Dystrophy (DMD) continues to send out ripples throughout the industry. On October 18, John Jenkins, director of the FDA’s Office of New Drugs, Center for Drug Evaluation and Research, gave a talk at the NORD Summit Meeting that directly focused on the decision.
On September 19, after a year-long battle filled with controversy and public outcry, the FDA approved Sarepta’s eteplirsen for DMD. DMD is a muscle wasting disease caused by mutations in the dystrophin gene. It is a progressive disease that usually causes death in early adulthood, with serious complications that include heart or respiratory-related problems. It mostly affects boys, about 1 in every 3,500 to 5,000 male children.
Beginning in January 2015, the approval process included postponements, public hearings that included 52 public commentators, including families and DMD children, and letters from members of Congress urging a DMD drug be approved, and a public letter from 36 DMD experts urging that eteplirsen be approved.
One of the key concerns over the drug is whether it can actually produce higher levels of dystrophin. The application for approval was essentially based on a 12-patient clinical trial with no placebo control group.
When an outside panel was split 7 for, 6 against approval, Janet Woodcock, Director of the FDA’s Center for Drug Evaluation and Research (CDER), pushed approval through. That was despite strong opposition from others on her staff, including Ronald Farkas, who left the agency to join Parexel International , the agency’s acting chief scientist, Luciana Borio, and Ellis Unger, director of the office of drug evaluation.
In his recent talk, Jenkins said, “The path taken by Sarepta is NOT a good model for other development programs.”
At a higher level, the controversy of this approval revolves around how flexible, and in what ways, the FDA should be in drug approvals for life-threatening diseases with no other treatments. Many scientists and individuals at the FDA believe that the FDA should set a fairly rigid bar of scientific proof that needs to be met. Period.
Others push for flexibility. Woodcock has said the FDA must be “prepared to be flexible with respect to a devastating illness with no treatment options.”
That thinking appears to be along the lines of: The company hasn’t proved that it works, but it’s the only one we’ve got, so approve it.
In his talk, Jenkins said, “In many cases, randomized controlled clinical trials represent the fastest way to determine if a drug is effective.” He added that biopharma companies should “randomize as early as possible in development to avoid potentially misleading and uninterpretable findings from open-label trials.”
And directly responding to Woodcock, he said, “Flexibility in FDA regulations does not mean marketing approval prior to demonstration of substantial evidence of effectiveness. NOT as a ‘rescue’ for a failed program.”
The Sarepta approval may or may not have set a bad precedent. BioMarin Pharmaceutical ’s Kyndrisa (drisapersen) to treat DMD was rejected in January. But after the Sarepta approval, there are indications that BioMarin is considering appealing that decision. Which seems like a longshot. BioMarin ran three clinical trials and two didn’t meet their primary endpoint, which involved getting patients taking the drug to walk further in six minutes. It also had potentially deadly side effects that included low platelet levels, kidney toxicity, and ulceration, scarring and atrophy at the injection sites.
Yet, Sarepta, for its part, is taking eterplirsen, with the trade name Exondys51, to market with a price tag of $300,000. Sarepta’s was running $28.15 on September 16, then jumped after its approval to a high of $62.35 on October 5. It’s dropped off since then, currently trading for $47.82.
