FDA Faces Sensitive Challenge With Review of DMD Drug

The blanketing of snow on the East Coast this past weekend prompted the postponement of a high-profile US Food and Drug Administration (FDA) advisory committee hearing for a Duchene Muscular Dystrophy (DMD) drug that is stirring up public controversy and will eventually lead to an up or down decision testing FDA’s resilience to public pressure.

The advisory committee meeting, which the Jett Foundation, a DMD advocacy group, said Tuesday will likely be rescheduled within the month, will deal with a treatment for DMD, a rare and fatal genetic disorder afflicting about 15,000 young boys in the US, with no approved drugs to treat it.

Briefing Documents 

That postponement of the Peripheral and Central Nervous System Drugs Advisory Committee Meeting came almost a week after FDA released briefing documents (as it always does before such a hearing) outlining some serious concerns about the trial run by the developer, Sarepta Therapeutics, of the drug known as eteplirsen.

In the statistical review section of the documents, FDA officials said at the outset that the data on just 12 subjects “overall, did not provide statistical evidence to support the efficacy of eteplirsen.” Agency reviewers go on to highlight study design and statistical analysis issues from the only randomized controlled study, noting that it "can only be considered as exploratory."

The release of the documents, viewed by nearly every onlooker to be extremely negative, caused Sarepta’s stock to be cut in half, resulted in at least one investor lawsuit and pushed the company to file additional clarifications of “key inaccuracies in the FDA briefing document.”

Emotions Run High

Parents of some of the young boys involved in the Sarepta study, who have been vocal supporters of the drug’s approval, also took to the Web to refute FDA’s briefing documents, claiming they were “inaccurate, misleading, & deceptive” and harmful to “patients-not just any patients-but innocent children who are now considering and dreaming of driving, entering college, and choosing a career path.”

Other parents of boys with DMD have lobbied FDA to approve the drug via petitions, noting that most of those with DMD don’t make it to the age of 30.

The emotions of these parents have even spurred some journalists covering Sarepta to turn into activists for the company and the drug’s approval, though others are calling on FDA to wait for more data.

Some commentators also point to FDA’s approval of the previously rejected female sexual desire disorder drug Addyi (filbanserin) as proof that the agency can cave to public pressure and may do so with Sarepta.

Still, the overall perception going into the Sarepta advisory committee meeting, which is expected to draw not only a crowd of patient advocates but congressmen and FDA’s CDER Director Janet Woodcock, is that the drug will not be recommended for approval and will not be approved. That rejection would come on the heels of FDA’s rejection of BioMarin Pharmaceutical’s DMD drug, after the agency said the drug’s trial data failed to show a clinical benefit.

FDA's deadline for issuing a decision on eteplirsen is 22 February, though the delayed advisory panel could extend that timeline.