Is Sarepta special? Or has the FDA set a new precedent for how it approaches treatments for devastating diseases with few options?
On Thursday, the FDA announced it was expanding the allowed use of Sarepta’s gene therapy for Duchenne muscular dystrophy to a far wider group of patients. The treatment, Elevidys, will now be available to those ages 4 and older, an expansion that’s expected to make it available to 80% of patients with the disease, according to the company.
But the move by the FDA, in which CBER Director Peter Marks overruled his own staff, is prompting new questions about just how the agency will approach similar drugs in the future.
On Monday, ahead of the decision on Sarepta’s gene therapy, Endpoints News asked Marks about disagreement within the FDA. He said there’s a “spectrum” of views within the agency, but “our job as leaders is to help people feel like we’re going to lead them in a place where we get more products across the finish line.”
“I’d like to move it from the baseline further towards a little bit of willingness to take risks or a moderate amount more toward taking more risks and hopefully people will come along,” Marks said. “That’s where we’re hoping to head in the coming months to years.”
Staff overruled
Memos accompanying Thursday’s action showed how Marks overruled two top FDA officials, including his deputy Nicole Verdun — the director of the Office of Therapeutic Products which the agency established last year under Marks to deal with a flood of new cell and gene therapies.
Verdun’s lieutenant Lola Fashoyin-Aje recommended rejecting the therapy and running a new clinical trial. Fashoyin-Aje said there wasn’t enough evidence to show benefit in the patient populations for which Sarepta asked for approval, including the initial accelerated approval population of boys ages 4 and 5. Verdun, who like Marks has spoken about working more closely with patient groups, agreed with Fashoyin-Aje’s recommendation.
Elevidys failed to meet the primary endpoint last year in a confirmatory study, but Sarepta cited key secondary endpoints suggesting the therapy may improve boys’ ability to stand and walk.
In his memo, Marks called the secondary and exploratory data points “compelling,” and called the benefit-to-risk ratio “favorable, taking into consideration the severe unmet need and existing uncertainties.”
“I’m just stunned that one person can override the decision of multiple career staff at the FDA with varied expertise,” said Reshma Ramachandran, an assistant professor of medicine at Yale University. “That is troubling to see that sort of power can be wielded this way.”
But for patient advocates, Marks’ action shows he understands their plight. “Time matters to every single patient with a rare disease,” said Pat Furlong, who founded and leads the nonprofit Parent Project Muscular Dystrophy. “And Dr. Marks’ flexibility indicates that he gets that.”
“Older boys and men, like my son Hawken, have an urgent need for treatments that can delay the progression of the disease. They don’t have the luxury of time to wait for a treatment that is perfect,” wrote Debra Miller, founder and CEO of the group CureDuchenne, in an email to Endpoints, adding that it’s an individual discussion for each patient to have with their providers.
Physicians who treat Duchenne patients and other rare disease drug developers likewise applauded the expanded label. “I was absolutely elated,” said Jamie Eskuri, a pediatric neurologist at Gillette Children’s Hospital in Minnesota.
Aravindhan Veerapandiyan of the University of Arkansas for Medical Sciences echoed the excitement, but also noted that more data are needed in older, non-ambulatory boys, pointing to potential heart risks with the therapy.
Veerapandiyan worked on Sarepta’s clinical trials, while Eskuri served on a one-time advisory board for Elevidys in 2022.
“It’s a really positive sign for Duchenne, but also a positive sign for some of the other diseases,” said Emil Kakkis, CEO of the rare disease company Ultragenyx. “It just allows the whole ecosystem of development for rare diseases to accelerate.”
A vast expansion
What’s certain is Marks’ single-handed decision has irrevocably changed the landscape for Duchenne muscular dystrophy treatment, as well as the prospects of Sarepta as a company.
“At the risk of sounding immodest, Sarepta knows how to work on behalf of Duchenne patients,” Sarepta CEO Doug Ingram said on an analyst call Friday morning.
The label expansion sent Sarepta’s shares up 30% Friday, giving it a market value of around $15 billion. Sarepta said Friday that it was not changing the therapy’s $3.2 million list price in the US.
Wall Street analysts projected that the expanded label could mean $1 billion in sales from Elevidys for Sarepta this year, and several billion in annual sales in future years.
Physicians, meanwhile, are expecting many more patients. Eskuri said that at her practice at Gillette Children’s Hospital, they treated three Duchenne boys with Elevidys in the past year under the initial approval for boys ages 4 and 5.
With the expanded label, Eskuri estimated that around 100 patients from her practice are now eligible, barring a handful who may have neutralizing antibodies to the therapy or certain mutations. Whether insurance companies will cover as broadly as the FDA’s expanded approval will also play a factor.
Editor’s note: This story was updated with Aravindhan Veerapandiyan and Jamie Eskuri’s relationships to Sarepta.