FDA bats back Sarepta’s counterattack as a final showdown looms over Duchenne drug

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Sarepta’s regulatory team came out swinging after the FDA issued a harsh review of its Duchenne muscular dystrophy drug last January. But in a blow-by-blow account of the exchange that occurred between the drug developer and regulators, the agency continued to insist that Sarepta’s application failed to provide convincing evidence that the drug worked as billed.

These new FDA documents arrived just days ahead of Monday’s rescheduled panel review of eteplirsen. And while the agency carefully outlined the biotech’s defense of its data and its drug, the FDA signaled that it has no intention of retreating. “(W)e do not agree with the applicant’s characterization of inaccuracies in the initial FDA briefing document.”

Sarepta’s shares plunged more than 40% as the agency’s continued negative tone sunk in.

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In recounting the biotech’s case on using immunofluorescence results to demonstrate dystrophin distribution, a key part of its case that their drug provides a real benefit to patients, the agency concluded that Sarepta never was able to estimate dystrophin content in a meaningful way; “we believe the results reported by the applicant on this measure do not establish that a significant increase in dystrophin occurred in response to eteplirsen treatment.”

Once again the agency picked apart Sarepta’s chosen historical data that was used to illustrate an improved physical performance by a handful of boys taking eteplirsen. And the FDA questioned the way Sarepta presented some of its results, noting that “it is concerning that images used to provide evidence of an effect of eteplirsen greatly exaggerate the immunofluorescence signal from the muscle samples.”

Regulators raised the issue that results of the company’s 6 minute walking test could have been influenced by the investigators administering the tests, just as atypical results from the historical data used raised questions about accurately making comparisons.

The agency highlighted a lack of objective clinical data that could be used to qualify for an accelerated approval, highlighting several exchanges where the FDA had urged the company to undertake a larger, randomized study that could provide clear evidence of success. The FDA said it remains flexible, but “flexibility does not mean approving drugs for which substantial evidence of effectiveness has not been established.” 

The FDA did sound a note of open mindedness, though, specifically stating that no “final conclusions” had been made yet. But that may prove small consolation to the company’s many supporters.

The last few months have proven to be excruciating for patients and families, who currently have nothing to turn to to slow or stop a disease that first cripples and then kills boys. BioMarin tried and failed with drisapersen, with an FDA rejection landing in January. PTC Therapeutics never made it through the door with their therapy, as regulators refused to even file an application they found too weak to warrant careful consideration.

Eteplirsen is the only near-term prospect for an approval now, and hundreds of advocates are expected to descend on the FDA panel review on Monday to offer their support.

With data lacking, lobbying may be Sarepta’s last, best hope of turning things around. But as of now, that’s a very tall order.

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