Although Sarepta Therapeutics managed to defuse a brief stalemate with the FDA earlier this week, the U.S. drug regulator is reportedly going to put the company to work in order to affirm the safety of its Duchenne muscular dystrophy (DMD) gene therapy Elevidys.
Sarepta would need to conduct new analyses to validate the safety of Elevidys—which has had U.S. shipments paused by the company over a mounting string of controversies—to the FDA, Endpoints News and Bloomberg separately reported Thursday, citing an unnamed senior FDA official.
As for what those studies might look like, Sarepta could alter its dosing or manufacturing process for Elevidys and test it on the next dozen or so patients in an effort to produce more favorable liver function test results, the official said in an update to Endpoints’ original report. That would be a much more manageable requirement than needing to run a new clinical trial, which would also run against established regulatory precedent for a fully approved drug.
That said, no one at the FDA thinks the treatment should return to market based on current data, an anonymous FDA official told Bloomberg.
A Department of Health and Human Services spokesperson did not explicitly confirm the report when reached by Fierce Pharma for comment, instead stating that the FDA is “looking at all the tools we have" when it comes to evaluating Elevidys' market position.
Sarepta, for its part, had not responded to Fierce Pharma’s request for comment by the time of publication.
A company spokesperson told Endpoints that Sarepta’s “focus is on serving patients” and that it will “work within the ordinary and well-established FDA channels and procedures, and look[s] forward to completing the label supplement process.”
The report follows a brief back-and-forth between Sarepta and the FDA over a voluntary pause on U.S. shipments of Elevidys in all indications.
After reports surfaced last week that a third patient had died after receiving a Sarepta gene therapy—in this case an investigational treatment distinct from but related to Elevidys being assessed in a different form of muscular dystrophy—the FDA on Friday asked the company to voluntarily stop sending out commercial doses.
Sarepta initially pushed back, stating that it would continue to ship Elevidys to ambulatory DMD patients based on its own “comprehensive scientific interpretation of the data,” before ultimately relenting and initiating a shipment pause earlier this week.
Sarepta said the pause will provide it with “the necessary time to respond to any requests for information” and to finish updating Elevidys’ safety labeling under an agreement with the FDA to add a black box warning for acute liver injury. The company is also looking to add an updated risk management scheme to the gene therapy’s label.
Although an FDA spokesperson last week confirmed with Fierce Pharma that an unnamed federal official is “taking a hard look at pulling [Elevidys] from the market,” it is important to note that Sarepta’s gene therapy hasn’t been withdrawn and that a shipment pause is not equivalent to the drug having its approval pulled.
Crucially, it remains unclear whether the FDA has the authority to revoke Elevidys’ approval or demand a full market withdrawal, given that such actions are typically reserved for drugs that have won green lights through the agency’s accelerated pathway, Jefferies analysts wrote in a Sunday note to clients. Elevidys converted its accelerated approval into a full one in ambulatory DMD patients—or those who can walk independently—last June.
It would be “unprecedented” for the FDA to require Sarepta to conduct another Elevidys clinical trial in ambulatory DMD patients given the drug’s approval status, analysts at William Blair wrote Thursday following Endpoints’ report. The two Elevidys deaths occurred in non-ambulatory patients, for whom Sarepta had already stopped shipments earlier this year.
Further, “it could set a dangerous precedent for the gene therapy space broadly, given an Elevidys-related death wasn’t observed until approximately 800 patients bad been treated, including 100 non-ambulatory patients,” the William Blair team wrote.
It is possible that Sarepta could lift its Elevidys shipment pause before the end of the year, though that outcome is far from certain, the analysts added.
Sarepta’s Elevidys imbroglio began in March when the company reported that a patient had died of acute liver failure following treatment with the approved gene therapy. A second Elevidys death by the same cause was reported in June, prompting the company to suspend use of the treatment in DMD patients who can’t walk independently.
At that time, Sarepta also started working on a new mitigation strategy leveraging the immunosuppressant sirolimus to help Elevidys patients manage liver toxicity.
Unlike the first two fatalities, which occurred in teenage boys with DMD, the most recent death—also due to acute liver failure—was reported in a 51-year-old man with limb-girdle muscular dystrophy type 2D/R3. The patient had received an investigational gene therapy called SRP-9004, which uses the same viral vector as the approved Elevidys.
Sarepta last Wednesday shelved the bulk of its gene therapy pipeline, including SRP-9004, but did not disclose the death, which has helped fuel a sustained assault on the company’s share price in the ensuing days.
The company’s stock was down nearly 21% in Thursday afternoon trading.
Editor's note: This story was updated at 3:37 p.m. ET on July 24 with additional information from Endpoints' report.