By Patrick Wingrove
NEW YORK (Reuters) -The U.S. FDA approved a pricey rare disease drug in September despite findings by its data reviewers that the treatment, while safe, was no more effective than a placebo,
a Reuters review of agency documents found.
The urgent need among patients, along with some signs of improved motor skills, helped drive the agency's decision, the documents show.
The Food and Drug Administration on September 19 gave its backing to Stealth Biotherapeutics' elamipretide, which will be sold as Forzinity and priced at up to nearly $800,000 a year. It will be the first treatment for Barth syndrome, although FDA documents show nearly a dozen reviewers recommended against approval.
The Massachusetts-based company had for years been seeking approval for elamipretide to treat the life-threatening mitochondrial disorder that affects about 150 people in the U.S., mostly males. The disease typically presents as severe heart failure in infancy and often leads to premature death.
The FDA declined to consider elamipretide for full approval in 2021 and rejected the company's application in May of 2025 before suggesting Stealth apply for an expedited process. It approved the drug just over a month after Stealth refiled its application.
Stealth CEO Reenie McCarthy said the FDA made an informed, science-based decision to approve Forzinity, recognizing both the strength of the data and the urgent unmet need in Barth syndrome.
The Trump administration has made rare disease drug approvals a priority, and had just introduced a new policy that allows applications to move forward based on one strong study and other confirmatory evidence.
FDA drug approvals are not typically contentious among evaluation teams, according to experts and a Reuters review of approval documents from 2024, although agency chiefs have used their authority in the past to push through approvals.
DOCUMENTS REVEAL SHORTCOMINGS
Documents show that FDA office chief Hylton Joffe signed off on the accelerated approval, citing a 10-person, 192-week study in which the drug boosted knee strength by more than 45%, as well as the disease's rarity and severity.
Reviewers listed various concerns, including that the drug failed to beat a placebo in a 28-week, late-stage study, and that the non-placebo study Joffe cited failed to show a direct link between the treatment and improvements.
Placebo patients improved almost as much as those on Forzinity in a six-minute walk test - the study’s main measure. It also failed to show significant gains on secondary goals like sit-to-stand tests, reviewers said.
FDA clinical team leader Charu Gandotra recommended against approval to Joffe, arguing Stealth's data did not "provide substantial evidence of effectiveness to support traditional or accelerated approval."
The U.S. Department of Health and Human Services, which oversees the FDA, did not respond to a request for comment. Joffe and Gandotra did not immediately respond to similar requests.
PRESSURE TO APPROVE
Lawmakers, physicians and patient advocates pressured the FDA to approve the drug. More than 80 doctors signed an August letter to Commissioner Martin Makary urging immediate approval or a fast-tracked, two-month review.
At the heart of their appeals were families like those of Josanne Archibald, a 40-year-old patient navigator from New Jersey, who learned about the experimental new treatment for the genetic disease affecting her two sons and pushed to get her third unborn son treated soon after he was delivered.
At the time, Stealth hoped the drug could get approval for children ages two and older, based on data from treating critically ill infants on an emergency basis, but the approval was limited to adults and children who weigh at least 30 kg (66 pounds).
Archibald said her youngest son Josiah, now almost two, was in critical condition when he was born, even worse than his brother Mason, who required a heart transplant at six weeks old. After starting treatment, Josiah's heart function normalized and within five months he was strong enough to leave the hospital, she said.
"We're just blown by that... even the (therapists) are amazed at how well he's doing and how strong he's getting day by day,” Archibald said.
Dr. Hilary Vernon, who led Stealth's trial and runs the Barth syndrome clinic at Kennedy Krieger Institute in Baltimore, told Reuters Forzinity was linked to real gains in muscle strength, endurance, and quality of life. These outcomes, she said, would be unlikely without the treatment, given the nature of the disease.
She was among the doctors who signed the letter urging approval.
Lawmakers from Colorado, Florida, Georgia and elsewhere also sent Makary letters pressing for fast approval.
The FDA has bowed to pressure from patient advocates for rare disease treatments before despite internal scientific disagreement, including when it tried to remove Sarepta Therapeutics' gene therapy for Duchenne muscular dystrophy from the market earlier this year.
"FDA's internal disagreement over the adequacy of scientific evidence for ultra-rare diseases often cannot win out over patient demand for access when there are no other treatment options available for a devastating illness," said FDA lawyer Rachel Turow.
Stealth CEO McCarthy told Reuters the company expects to seek traditional approval based on results of a four-year follow-up study required by the FDA as part of the accelerated approval. Stealth plans to launch Forzinity in December.
The drug, which will be Stealth’s first marketed product, is listed at over $15,000 per 280 mg vial, enough for one to two weeks of therapy depending on individual needs.
Like many treatments for ultra-rare diseases, Forzinity's high price is aimed at helping the company recover its research and development costs. Stealth said it is in early discussions with health insurers over coverage and will have a program to reduce out-of-pocket costs for patients.
(Reporting by Patrick Wingrove in New York; Editing by Caroline Humer and Bill Berkrot)
