| | | The Sarepta Mugging and Drug Innovation
The Trump FDA tries to kill a therapy that has helped boys with a deadly diagnosis.
American companies are racing to develop gene therapies that treat dreadful maladies, with often spectacular results. But progress isn’t inevitable, and the story of a drug for a rare condition suggests that the Trump Administration is taking a bad turn that will chill investment in new drugs.
The Food and Drug Administration this month asked Sarepta Therapeutics to suspend shipments of its gene therapy Elevidys. The drug treats Duchenne muscular dystrophy, and few ailments are more wrenching: Young boys lose muscle function as the disease progresses and eventually need wheelchairs, often before they’re teenagers. Some die in their 20s.
The putative reason for the pause is safety. Two patients have died from acute liver failure after receiving the drug. Most recently, a 51-year-old man with a different condition died after receiving an experimental gene therapy made by Sarepta. The FDA said Friday it is investigating the death of an 8-year-old boy, which the company says was previously known and ruled unrelated to the gene therapy.
***A tip that something is off here is that the FDA is eliding distinctions about these tragedies. The company says nearly 1,000 patients have been treated with Elevidys, a large sample size for a nascent gene therapy. Both Duchenne patients who died suffered from advanced disease and could no longer walk when treated. Sarepta more than a month ago paused shipments to patients who can no longer walk.
It assembled a panel of experts to understand the risks and look at adding an immunosuppressant regimen to prevent liver overreaction for some patients. The company says it will add a black-box warning to help clinicians and patients make an informed choice. Investors are unhappy that they learned about the clinical trial death belatedly, which was a corporate PR debacle. But the company says it informed the FDA weeks ago when it happened.
Yet the FDA has demanded the company stop shipping the Duchenne drug for all patients. Younger boys who can still walk are in better health and receive a lower weighted dose. They also have more to gain from prompt treatment—potentially more days to throw a ball or climb stairs. Therapies always carry risks, but patients and their families often prefer them to the brutal certainty of decline.
The company initially refused to halt all shipments but later agreed. Yet it isn’t obvious what the company can now do to receive a clean bill of health. A senior FDA official told the press last week that the drug faced an “arduous and treacherous” path back to market and that the company suspended shipments because the agency had “a gun to its head.”
Partial points for honesty that this is a regulatory mugging. What adds to this perception is that a self-professed Bernie Sanders acolyte who dislikes the drug is running FDA’s gene therapy shop. Vinay Prasad, director of the FDA’s Center for Biologics Evaluation and Research, has lambasted his predecessor Peter Marks for twice overruling agency staff to approve the Duchenne therapy.
Dr. Marks made good decisions to prioritize speed and patient choice over certainty on the data. The FDA noted in an approval last year that a large, randomized trial didn’t meet its primary aim.
But boys improved on secondary measures such as “time to rise from the floor, 10-meter walk/run, time to ascend four steps.” There is “nothing ambiguous about these improvements,” as a father of a boy who received the therapy put it at a FDA hearing. Dr. Marks noted in his memo approving the drug that such secondary endpoints had been used to support prior drug approvals as primary endpoints.
This is the risk tolerance the agency is supposed to show, particularly for devastating and rare diseases like Duchenne with few or no treatments. Dr. Prasad has called Dr. Marks a rubber stamp who did “more for Sarepta than the CEO” and complained on his Substack that the Duchenne drug is among “the most costly” in history.
That lays bare the real argument here, which isn’t about whether the safety risks in gene therapies can be managed. It’s a claim that the drug is an expensive false hope for desperate families who Dr. Prasad thinks can’t be trusted to make their own decisions about risks and benefits. That paternalism is familiar from Democratic administrations and the FDA bureaucracy.
President Trump had a different policy in his first term when he made a cause of the 2018 “right to try” law. That measure had practical limits but was important as a policy statement that patients should be the first priority of regulators.
***The stakes here for drug development are enormous if Mr. Trump’s regulators crush a drug that has already won FDA approval. Several early gene therapies aren’t home runs, but drug development is iterative and builds on trial and error. Forget about better drug iterations if the agency kills a company for an emerging safety warning in some patients.
FDA Commissioner Marty Makary has been talking about faster approvals and more flexibility for innovative drugs, but investors in the next cure bet capital based on the agency’s actions. Meanwhile, families facing a terrible diagnosis are left wondering if the only gene therapy on the market will be an option for their sons. If Americans wanted fewer novel treatments, they could have elected Kamala Harris. |
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