How the FDA could boost gender-affirming care

• A small nonprofit formed this year with the goal of obtaining FDA approval of the drugs for gender-affirming care believes the agency's formal OK could strengthen legal protections for the treatments and boost insurance coverage.

Catch up quick: Estrogen and testosterone therapies have been approved by the FDA for other purposes. For instance, estrogen is approved as a hormone replacement therapy for patients going through menopause.

• The off-label use of hormone therapies for gender-affirming care is safe and supported by leading medical groups, including the American Medical Association and the American Academy of Pediatrics.
• Research has shown that receiving gender-affirming care is associated with better mental health, including lower risk of depression and self-harm or suicidal thoughts, among transgender youth.
• In recent years, Republican lawmakers in at least 22 states have passed laws banning or limiting gender-affirming care for minors, some of which include restrictions on hormone therapy.
• Groups fighting against gender-affirming care have criticized the prescription of hormone therapies and puberty blockers for kids and petitioned the FDA to review off-label use.

Driving the news: The Research Institute for Gender Therapeutics (RIGT) has proposed a late-stage clinical trial of estradiol, a common form of estrogen, as a treatment for gender incongruence. The FDA last month provided initial feedback on the trial design.

• "We're excited that now we have really good visibility on how to go about pursuing" full FDA approval, said RIGT co-founder Brad Sippy.
• The company originally planned to make the trial double-blind, in which the researchers and participants during the study period don't know who's received the treatment or a placebo.
• After receiving FDA input, the nonprofit's trial will not use placebo controls and will include participants age 13 and older, Sippy said.
• The feedback "actually kind of simplifies the study design, and makes it perhaps ease more easy to recruit because people don't have that concern about potentially being assigned to placebo," he said.

Before starting a trial, the group would still need the FDA's formal OK on trial design and the approval of a board that reviews safety and ethical concerns, Stat noted.

• The nonprofit still needs to raise money to conduct the trial and hopes to start it in 2025. RIGT expects it could take three years before the FDA could approve estradiol.
• RIGT also plans to eventually pursue FDA approval of testosterone for gender-affirming care.

Having clinical trial evidence and FDA approval could strengthen the case against state bans, Sippy said.

• "We're not the ACLU, you know, so we're not going to go arguing with the state of Montana on behalf of trans people necessarily, but the studies that we do could be very useful to [advocates] when they do have those arguments," Sippy said. "We kind of have a baton that we can pass to them."

What they're saying: An FDA spokesperson said the agency is limited in what it can say about a drug sponsor's development program, while noting that the FDA's advice "should not be interpreted as FDA necessarily proposing or recommending a different approach."

FDA approval of hormone therapies for gender-affirming care wouldn't change the way doctors prescribe them or patients use them, but it would bring additional legitimacy to the treatment and could make insurance companies more willing to cover the drugs, said Madeline Deutsch, director of the University of California, San Francisco's Gender Affirming Health Program.

• Coverage policies for gender-affirming hormone therapies vary widely, though nearly half of states prohibit employers from refusing coverage of transgender-related health care benefits.

Between the lines: FDA approval could set off a new round of legal challenges over access to the treatments.

• "Courts are the new battleground for political influence over drugs that are highly politicized," said Delia Ann Deschaine, a lawyer at Epstein Becker Green who advises clients on FDA policies.
• She pointed to the ongoing legal battle over access to the abortion pill mifepristone, which the Supreme Court on Wednesday agreed to review. The justices will hear a lawsuit challenging FDA moves that expanded access to mifepristone in recent years.
• That case has factored into how RIGT is approaching clinical trial design.
• "We want to have something that's robust enough that, if some critic comes back later on, we can say we did everything in the normal course of business," Sippy said.