Sarepta finally crosses the finish line with controversial DMD med Exondys

FDA

Sarepta Therapeutics has been waiting, hoping--and lobbying--for approval of its Duchenne muscular dystophy (DMD) drug eteplirsen for years. And now, it’s ready to launch.

Now called Exondys 51, the drug is approved for a small fraction of patients with DMD, and it’s not likely to need much marketing. The drug has been a regular in TV coverage and newspaper headlines, and patient groups are well aware of the med; in fact, they were instrumental in lobbying the FDA to approve it.

The approval comes after considerable controversy, as patient groups enlisted lawmakers in pushing the FDA to bless the drug despite its considerable doubts. Hundreds of advocates showed up at an FDA advisory panel meeting where Sarepta’s data were reviewed, arguing on behalf of the boys whose conditions had improved while taking the drug. And when the panel itself voted against approval, the pressure only intensified.

An intra-agency argument followed at the FDA, and the agency delayed its decision--once again--in May. Now, the agency has erected one hurdle for Exondys 51 as it enters the market: It’s requiring Sarepta to quickly start work on a follow-up trial to confirm the drug’s clinical benefit, the agency said in a statement.

“If the trial fails to verify clinical benefit, the FDA may initiate proceedings to withdraw approval of the drug,” the statement said.

Of course, as the debate over data shows, confirmation of clinical benefit has been elusive, at least in the trials Sarepta has conducted thus far. As a small sub-population of a rare disease--Exondys 51 is cleared for patients with a particular genetic mutation that makes them amenable to exon 51 skipping, hence the name--trial-eligible patients have been hard to come by. Meanwhile, the FDA has repeatedly taken issue with Sarepta’s study designs.

“A clinical benefit of Exondys 51, including improved motor function, has not been established,” the FDA said.

The approval is based on a surrogate marker instead: The FDA decided that Sarepta’s data “demonstrated an increase in dystrophin production” that is “reasonably likely to predict clinical benefit in some patients.”

Patient advocacy groups cheered the approval, and Sarepta’s launch runway is clear. As Endpoints reminds us, Exondys 51’s advent follows rejections for two potential rivals. BioMarin sidelined its candidate, Kyndrisa, after the agency refused to approve it, and PTC failed to win a hearing at the agency at all.

As Exondys 51 rolls out, the FDA and the biopharma community will be rehashing the drug’s path to approval--particularly the intense lobbying that marked its final steps to market. Even before Exondys 51 won its nod, pharma-watchers were debating--and warning--that an FDA approval could have unintended consequences down the line as patients increasingly demand a bigger voice in the agency’s decisions.

In this sense, Exondys 51’s approval is reminiscent of Addyi’s FDA experience. The female libido drug won an approval despite some serious questions about side effects, amid vociferous lobbying from its developer, Sprout, and women’s groups. Now owned by Valeant, Sprout has struggled to get Addyi off the ground.

Addyi is very different from Exondys 51, of course; DMD is a debilitating, life-threatening disease with no treatment options. But the two decisions, taken together, may end up encouraging more public pressure for the FDA.

For its follow-up study, Sarepta is required to submit a draft protocol by next month, and to finalize that protocol by April 2017. Final data would be due by May 2021, the agency says.

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