Cambridge biotech Sarepta wins fast-track approval for the first muscular dystrophy gene therapy

Jonathan Saltzman and Robert Weisman, The Boston Globe, June 22, 2023

The Food and Drug Administration on Thursday approved the first gene therapy for Duchenne muscular dystrophy, a $3.2 million one-time treatment from a Cambridge biotech for a deadly inherited neuromuscular disorder that afflicts more than 10,000 boys and young men in the United States.

But amid skepticism from some scientists inside and outside the agency on its effectiveness and safety based on clinical trial data, the FDA limited the approval of Sarepta Therapeutics’ treatment to patients ages 4 to 5 years old who still have the ability to walk.

The closely watched decision came six weeks after a panel of outside scientific advisors voted, 8-6, that the benefits outweigh the risks. The agency didn’t have to follow the advice of the panel but usually does. The FDA had delayed its decision about a month while considering narrowing the scope of who would be eligible for the treatment.

The FDA’s ruling marked the first time that a gene therapy — a groundbreaking class of medicines that typically cost $1 million or more per patient — has won “accelerated approval.” That pathway greenlights a drug that treats a serious condition and fills an unmet medical need before large clinical trials have been completed, based on scientific evidence that the medicine will likely work.

At $3.2 million per patient, it’s one of the most expensive drugs ever approved by the FDA. Last November, the firm CSL Behring priced a gene therapy for hemophilia B at $3.5 million per treatment, making it the world’s costliest drug.

The company originally sought fast-track approval for all Duchenne patients who could still walk, which would have included most under 10 and even some teenagers.

Debra Miller, founder of CureDuchenne, a national nonprofit, said she was delighted with the news.


But critics said they were disappointed in the ruling, arguing that the clinical data presented to FDA reviewers failed to show Sarepta’s drug provided significant benefits and pointing to potential safety risks.

“We think this [approval] is premature for a therapy we think at present is not effective,” said Michael Abrams, a senior researcher at Public Citizen’s Health Research Group. He said viruses used to deliver the gene therapy could form immune reactions in patients that would prevent them from taking more effective drugs that could later emerge. “You really are limiting opportunities potentially for these young kids,” Abrams said.

Agency staffers found “no statistically significant difference” between the gene therapy and a placebo for all but the youngest patients in the data from a trial, Mike Singer, a clinical reviewer for the FDA Center for Biologics Evaluation and Research, told the advisory panel on May 12.

Nonetheless, the FDA said Thursday that the therapy, which will be marketed as Elevidys, was a landmark in the fight against Duchenne.

“Today’s approval addresses an urgent unmet medical need and is an important advancement in the treatment of Duchenne muscular dystrophy, a devastating condition with limited treatment options, that leads to a progressive deterioration of an individual’s health over time,” said Dr. Peter Marks, director of the FDA’s Center for Biologics Evaluation and Research.

Sarepta said continued approval of the gene therapy may hinge on evidence from a confirmatory clinical trial. The firm has pledged to complete a late-stage trial, with some results expected late this year.


Dr. Anthony Amato, a Harvard professor of neurology who has treated Duchenne for decades and voted in favor of the gene therapy as a member of the advisory committee, called the videos part of the “compelling evidence this was effective” for some patients.

Six advisers concluded that the benefits didn’t outweigh the risks, however, including the possibility of liver damage, and some critics said the approval could raise false hopes. The data “doesn’t rise to the threshold of substantial evidence,” said Dr. G. Caleb Alexander, who teaches epidemiology and medicine at the Johns Hopkins Bloomberg School of Public Health

Sarepta’s gene therapy has rekindled a debate on the agency’s accelerated approval program. That initiative has hastened hundreds of drugs to market in the past 31 years. But it drew criticism in 2021 after the FDA cleared Biogen’s controversial Alzheimer’s drug Aduhelm, a costly medicine that some experts skewered as risky and ineffective.

As in the case of Sarepta’s gene therapy, families of patients with Alzheimer’s disease had implored regulators to approve Aduhelm. But doctors and hospitals balked at prescribing Aduhelm — and public and private insurers declined to cover it for most patients — making it a major commercial flop.

Diana Zuckerman, president of the National Center for Health Research, a nonprofit that analyzes clinical studies, called Thursday’s decision a compromise that she said failed to meet the FDA’s own approval standards.

“FDA scientists were clearly concerned that the treatment may not work, so the FDA compromised by approving the drug for 4- to 5-year-olds but not for older children,” she said. “I don’t think FDA should be making political compromises that undermine FDA standards and put patients at risk.”


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