FDA denies ultra-rare drug but offers path to ‘yes'

Politico

30-05-2025

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With help from Chelsea Cirruzzo
Driving The Day
ANOTHER BLOW TO BARTH'S TREATMENT — The FDA rejected Stealth BioTherapeutics' latest bid to market its proposed treatment for an ultra-rare genetic condition, though regulators have suggested a 'path' toward accelerated approval, the company said Thursday.
Stealth said the agency's complete response letter, which came four months after the FDA was initially scheduled to make a decision, didn't raise concerns with clinical safety data for the drug, known as elamipretide, to treat Barth syndrome by targeting underlying dysfunction in mitochondria, which are small energy-producing structures in cells.
CEO Reenie McCarthy told Prescription Pulse that agency requests for additional data in late 2024 led the biotech to expect approval, and the biotech believes they should have gotten accelerated approval based on what the FDA conveyed in the letter. 'They have all the information they need to make that decision,' she said.
HHS didn't respond to a request for comment.
Background: Barth syndrome — which can cause an enlarged and weakened heart, muscle weakness, recurrent infections and delayed growth — typically affects males and shortens their life expectancy by decades. About 150 Americans have the condition.
Stealth had suggested two ways the FDA could consider approving elamipretide — granting full approval based on the company's natural history study of disease progression absent medical intervention or endorsing accelerated approval based on a trial suggesting long-term improvements in muscle function. The FDA has agreed to consider muscle strength around the knees as a potential intermediate marker by which it could support accelerated approval and has asked Stealth to resubmit its application based on that endpoint, McCarthy said.
External FDA advisers voted last year to recommend approval for elamipretide despite persistent questions about its effectiveness. Stealth, rare disease advocates and patients with Barth syndrome and their caregivers have advocated for years for FDA approval, highlighting the difficulties in conducting trials for potential rare disease treatments that can't be studied in large populations.
Thursday's rejection seems 'inconsistent' with FDA Commissioner Marty Makary's recent comments about approving rare disease therapies based on plausible mechanisms and patient demand, McCarthy said. 'There's a bit of a disconnect' between those statements and the FDA's feedback, she said.
What's next: Stealth expects to meet with the FDA next month to discuss a postmarketing study it proposed in 2022 and 'gauge how serious they are,' McCarthy said. The company laid off 30 percent of its staff to save money for a potential FDA resubmission and to maintain elamipretide access for critically ill patients under the agency's compassionate use pathway.
McCarthy also raised concern about the FDA's stance that an accelerated approval would make the drug inappropriate to administer to newborns in acute cardiac distress, a population she said makes up two-thirds of Stealth's expanded access program. Half of early Barth syndrome deaths occur by age 1, per the company.
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Eye on the FDA
REPLACING COLOR ADDITIVES IN MEDS — The FDA quietly released draft recommendations for drugmakers that want to replace color additives in their approved drugs — potentially hinting at where the Trump administration will next focus HHS Secretary Robert F. Kennedy Jr.'s Make America Healthy Again energies.
The agency acknowledged that changing the formulation of a drug — including its inactive ingredients — is generally considered a major change. But the agency said replacing a color additive with another already listed in the FDA's color-additive regulations in many cases 'is unlikely to have an adverse effect on the identity, strength, quality, purity, or potency of the drug product.'
Replacing a color additive can 'generally be considered a moderate change' that can be requested via a 30-day supplement known as a CBE-30, according to the draft guidance published Thursday.
'If a manufacturer or an applicant intends to use a color additive that is not already listed in FDA's color additive regulations for the particular use, a petition must be sent to the Human Foods Program,' the draft guidance says. 'If FDA finds the color additive safe and suitable for such use, the additive will be listed in the color additive regulations.'
What's next: The FDA is taking comments on the draft guidance for 60 days.
AROUND THE AGENCIES
LAYOFFS ON HOLD — CDC layoffs planned for early June are being paused in the wake of a preliminary injunction, two employees at the agency, granted anonymity for fear of retribution, confirmed to POLITICO's Sophie Gardner.
CDC employees who were sent termination notices in April received an email from the agency's Office of Human Resources on Thursday, informing them that, because of a preliminary injunction, HHS 'is staying further action on any existing Reduction in Force (RIF) notices, including final separation of employees, at this time.'
The laid-off employees will remain on paid administrative leave 'or in their current employment status' until further notice, the email said.
An HHS spokesperson did not immediately respond to a request for comment.
Background: On April 1, amid a massive restructuring of HHS, around 18 percent of the CDC's workforce received termination notices. But legal challenges have complicated the reduction in force and the HHS reorganization, meaning the vast majority of those employees are still technically employed at the CDC, with most remaining on administrative leave.
Key context: On May 22, Judge Susan Illston of the federal district court in San Francisco issued a preliminary injunction that bars the administration from carrying out the reduction in force across 22 agencies — including HHS — that are defendants in the case. Federal employee unions, nonprofits and local governments are the plaintiffs.
The email sent to CDC employees cites Illston's injunction as the reason for the decision.
PROOFREADER WANTED — The White House blamed 'formatting issues' for errors in the citations of the recently released Make America Healthy Again report after a media report found studies in it that do not exist.
'We have complete confidence in [Secretary Robert F. Kennedy Jr.] and his team at HHS. I understand there were some formatting issues with the MAHA report,' White House press secretary Karoline Leavitt said Thursday.
Her remarks came after NOTUS reported that seven of the sources cited in the report, which said children's health is in crisis and blamed chemicals, lack of exercise and ultraprocessed foods, don't exist.
The report now lists five of its citations as 'corrected' or 'updated,' though that doesn't include the citations NOTUS reported as false.
'Some of the hundreds of citations in the report were formatted incorrectly or mistakenly referenced something other than what was actually intended,' a White House spokesperson told Pulse. 'That said, the content of the report is fully substantiated, and there is nothing in there that cannot be backed up; we did not conjure up any facts. Report has been corrected now.'
Pharma Moves
Laura Akowuah has joined Cooley as special counsel. She previously worked at the FDA for more than a decade in enforcement roles.
Document Drawer
The FDA approved Eton Pharmaceuticals' hydrocortisone oral solution Wednesday as a replacement therapy in patients ages 5 and older with adrenocortical insufficiency.
WHAT WE'RE READING
POLITICO's Erin Schumaker spoke with Dr. Wafik El-Deiry, a Brown University cancer researcher, about his campaign to lead the National Cancer Institute amid NIH funding cuts.
Two pharmacy benefit managers filed lawsuits Thursday challenging a recently passed Arkansas law they say would force pharmacies across the state to close, Modern Healthcare's Hayley DeSilva writes.
Texas lawmakers have sent legislation to Republican Gov. Greg Abbott's desk that would make it easier for parents to start the process of exempting their children from school vaccine mandates, The Associated Press' Jim Vertuno reports.
Several House Republicans are raising concerns about broad pharmaceutical tariffs potentially being placed on the industry, POLITICO's Ari Hawkins reports.