Although Sarepta initially appeared to have avoided the worst possible outcome for Elevidys—a market withdrawal—thanks to the gene therapy’s new black box warning, the FDA is signaling stronger misgivings about the approved drug in the wake of the death of a third patient who received one of the company's gene therapies.
Shortly after the close of Sarepta’s investor call Friday, Bloomberg News published an interview with Martin Makary, M.D., in which the FDA commissioner explained that he’s assessing whether Elevidys should remain on the U.S. market.
An agency spokesperson confirmed with Fierce Pharma that a federal official is “taking a hard look at pulling it from the market.”
Separately, FDA will now ask Sarepta to voluntarily halt all shipments of Elevidys—not just to non-ambulatory patients—an agency source familiar with the matter told Fierce Pharma. Reuters first reported the move.
As of publication, Sarepta has not responded to Fierce Pharma’s request for comment on both matters.
The company’s stock has plummeted more than 35% since market open, resting at $13.9 per share as of 2:30 p.m. ET.
The XBI, a biotech-specific index, has also slipped 1.9% in a manner that resembles Sarepta’s stock drop.
Elevidys scored an accelerated FDA approval in June 2023, quickly ranking as one of the world’s most expensive drugs with a list price of $3.2 million. As a gene therapy, the treatment was designed to be delivered as a one-time dose for the rare genetic disorder Duchenne muscular dystrophy (DMD).
The treatment was initially cleared in a small group of 4- or 5-year-olds who can walk, and the label was expanded last June to include all DMD patients, ambulatory and non-ambulatory, ages 4 and older.
The situation began to take a turn for the worse in March, when Sarepta reported that a patient had died from acute liver failure (ALF) following treatment with Elevidys.
“We are collecting additional information, but based on the current information from the treating physician, including the time since treatment and the clinical course, we cannot rule out the possibility that Elevidys was a contributing factor,” a Sarepta spokesperson said at the time.
In June, a second death was reported in a patient who’d received Elevidys. In both cases, the patients were non-ambulatory teenage boys who died after developing ALF.
The second fatality prompted Sarepta to suspend use of Elevidys in non-ambulatory patients in the U.S. commercial setting. The company was simultaneously seeking FDA approval of an enhanced mitigation measure leveraging the immunosuppressant sirolimus to help patients manage liver toxicity.
A little over a week after Sarepta announced the restriction on non-ambulatory patients, the FDA said it had launched an investigation into the two deaths following treatment with Elevidys.
The third gene therapy patient death—which Sarepta disclosed after multiple news reports Thursday—did not occur in a patient who had received Elevidys for Duchenne, but instead in a patient who received an investigational gene therapy for a subtype of limb-girdle muscular dystrophy. Both assets are engineered using the same adeno-associate virus vector, which has been linked to liver toxicity.
On Wednesday, Sarepta had said it was pausing development of the candidate, coded SRP-9004. The biopharma did not disclose the death at that time. Then, on a Friday investor call, the company’s CEO Douglas Ingram stressed that the decision was unrelated to the patient fatality.
Analysts expressed frustration over the fact that the patient death had not been discussed Wednesday, when Sarepta announced a major restructure that included 500 layoffs and the black box warning for Elevidys.
Elevidys’ approval was controversial from the jump, with former Center for Biologics Evaluation and Research (CBER) director Peter Marks, M.D., Ph.D., overruling negative opinions on the therapy from the FDA’s own review teams.
Meanwhile, Marks’ successor, Vinay Prasad, M.D., hasn’t hesitated to call the approval into question before his FDA appointment.
Marks “[o]verturned 3 reviewers to approve a [Duchenne] gene therapy that seems to be killing children and blowing their livers up,” Prasad wrote on X in March, shortly after Marks’ surprise dismissal from the regulatory agency.