Sarepta Duchenne gene therapy wins broader use from FDA

The Food and Drug Administration has substantially loosened limits on the first gene therapy for Duchenne muscular dystrophy in a decision that could greatly expand its use even as questions remain about its effectiveness.

The agency on Thursday made the therapy, called Elevidys and sold by biotechnology company Sarepta Therapeutics, available to people with Duchenne who are at least four years of age and have mutations in a specific gene, regardless of whether they can still walk.

For those who are still ambulatory the agency also converted Elevidys’ conditional approval to full, meaning its market availability in that setting is no longer contingent on additional tests. The clearance for Duchenne patients who are non-ambulatory is conditioned on the results of a Phase 3 study called Envision that’s currently underway.

“Today’s approval broadens the spectrum of patients with Duchenne muscular dystrophy eligible for this therapy, helping to address the ongoing, urgent treatment need for patients with this devastating and life-threatening disease,” said Peter Marks, head of the FDA’s Center for Biologics Evaluation and Research, in a statement.

Marks was a pivotal voice in Thursday’s decision. Documents published by the FDA show he overruled agency reviewers as well as high-ranking officials within his center who had advocated for a rejection of Sarepta’s application. Their skepticism stemmed from negative data Sarepta reported from testing of Elevidys, and their uncertainty that the treatment’s principal biological effect actually would translate to benefits.

In a memo, Marks wrote that he came to a “different conclusion” than his staff on interpretation of Sarepta’s data, and found the balance between risk and benefit to be favorable for Elevidys.

The FDA last June approved Elevidys only for certain boys between 4 and 5 years of age, a group Sarepta estimates to total about 400 in the U.S. each year. The new approval covers about 80% of Duchenne patients, a company spokesperson said.

That expansion could accelerate sales, which have totaled a cumulative $334 million, but recently have appeared to flatten. With a $3.2 million list price, Elevidys is one of the world’s most expensive medicines.

Duchenne is a progressive and fatal muscle-wasting condition that primarily affects boys. People with the disease gradually lose their ability to walk, typically during their teenage years, and can die from heart or lung complications in their 30s.

There is no cure. The steroids many people rely on to slow Duchenne come with side effects like weight gain and hormonal changes. So-called exon-skipping drugs, including three from Sarepta, are thought to only modestly alter the disease’s progression. The FDA also recently cleared a non-steroidal pill that can delay muscle loss and curb inflammation.

Patient advocates and drug developers have hoped gene therapy can do better, such as by halting or even reversing Duchenne’s inexorable assault on muscle function. Decades of research led to the development of several therapies, including Elevidys, that help the body produce a miniature form of the protein, dystrophin, that is lacking in people with Duchenne.

In testing, Sarepta’s therapy produced levels of that protein, called “microdystrophin,” well beyond what experts think could be beneficial. Advocates and researchers have also pointed to the favorable results some study participants have had on functional tests compared to historical data, arguing those findings prove the therapy works.

“What we’re seeing is stabilization of a disease that we’ve never been able to stabilize before,” said John Brandsema, a pediatric neurologist at the Children’s Hospital of Philadelphia, in an interview last year. “That is a tremendous achievement.”

But Elevidys hasn’t succeeded in a placebo-controlled trial, the gold standard for clinical research. In a Phase 2 study completed before it won approval, the therapy didn’t lead to a meaningful difference, versus a placebo, on a standard measure of motor function after one year.

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