The ‘abortion pill’ may treat dozens of diseases, but Roe reversal might upend research

Mifepristone, the FDA-approved abortion drug, might also treat conditions like cancer and PTSD. Proving it works in a post-Roe landscape could be a challenge.

The abortion drug mifepristone in an abortion clinic in Auckland, New Zealand in 2006.Phil Walter / Getty Images file

Dr. Nancy Klimas has spent the better part of her three-decade research career trying to find a cure for Gulf War illness. Military veterans with the unusual, unexplained illness  — which affects some 300,000 U.S. service members who fought in the 1991 Operation Desert Storm — suffer from a range of symptoms, including constant aches and pains, trouble concentrating, fatigue, respiratory issues and irritable bowel syndrome, all understood to stem from exposure to neurotoxic chemicals during combat.

Apart from symptom management — which she says is really just “chasing the tail of the dog” — there’s no treatment for Gulf War illness. And the clock is ticking: According to Klimas, director of the Institute for Neuro-Immune Medicine at Nova Southeastern University in Florida, the condition could turn into severe neurodegenerative disease if left untreated.

“I’m anxious to get in there and help these veterans as soon as we possibly can,” said Klimas, who is also the director of the Environmental Medical Research Program at the Miami Veterans Affairs Medical Center. “It’s already been 30 years.” 

Now, with a clinical trial for male veterans she’s launching at the Miami Veterans Affairs Hospital, she hopes this help will finally come. The study is testing out a combination of two drugs, both already approved by the Food and Drug Administration for different uses.

Dr. Nancy Klimas.Courtesy Dr. Nancy Klimas

One is etanercept, or Enbrel, a drug for arthritis. The other is mifepristone — better known as the abortion pill.

If the clinical trial is successful, it could be the first step toward bringing these veterans some relief, Klimas hopes. But now that the Supreme Court has overturned the legal right to abortion established in Roe v. Wade, researchers studying mifepristone for uses outside abortion could face their own set of challenges.

A versatile drug 

Since its approval by the FDA in 2000, the pills mifepristone, together with misoprostol, have been a safe and effective option for women seeking abortion during the first 10 weeks of pregnancy. Mifepristone is now used in more than half of the abortions in the United States, according to the Guttmacher Institute, a research group that supports abortion rights. The drug blocks progesterone, a hormone needed for the pregnancy to grow. Misoprostol causes cramping and bleeding to empty the uterus.

A combination pack of mifepristone and misoprostol tablets, two medicines used together for a medication abortion.Elisa Wells / Plan C/AFP via Getty Images file

While mifepristone is most well-known for its use in medication abortion, its potential uses go beyond ending early pregnancies. 

That’s because it has multiple biological effects, which explains why it could work for conditions as unrelated as veterans with brain injuries and pregnant women seeking abortions. In addition to blocking progesterone, it also blocks the hormone cortisol

Cortisol is often called the stress hormone, since it’s released in response to stress. But cortisol also plays a key role in regulating blood pressure, blood sugar, metabolism, inflammation and sleep cycles, meaning that too much cortisol can contribute to a host of illnesses. Having a safe, effective way to block the receptors cortisol needs in order to act on these systems has been valuable for doctors who treat all sorts of conditions.

At a slightly higher dosage than the one approved for abortion, mifepristone is also FDA-approved to treat Cushing’s syndrome, a rare disease marked by excess cortisol.

“It’s a very good drug, and a very potent drug,” said Dr. Atil Kargi, an endocrinologist at the University of Miami who has been using mifepristone to treat his patients with Cushing’s syndrome since it was first approved for that use in 2012. “And there’s no long-term toxicity that we’re aware of.” 

“This chemical … yes, it causes abortion, but it also does a lot of other amazing things,” said Leslie Edwin, a patient and president of the Cushing’s Support and Research Foundation, who was diagnosed with the disease in 2012. Edwin said she relied on mifepristone for 18 months to help manage the effects of excess cortisol in her body, including severe weight gain and type 2 diabetes.. “I was grateful that I had an option for a cortisol controller, and that it worked for me,” she said.

“This is the only drug like it on the market,” Klimas said. “If you took this one away, it would be taking away a great big tool.”

“This is the only drug like it on the market,” Klimas said. “If you took this one away, it would be taking away a great big tool.” 

Drug companies, including Corcept Therapeutics, which markets mifepristone for Cushing’s under the name Korlym, are working on new drugs that block cortisol but not progesterone, but those still have a long way to go before they’re available.

Apart from its two FDA-approved uses, mifepristone is also being investigated in clinical trials for breast cancer, brain cancer, prostate cancer, alcoholism, post-traumatic stress disorder and depression, among other conditions. 

Dr. Rita Nanda, the director of breast oncology at the University of Chicago, is running several breast cancer clinical trials looking at the effects of mifepristone and combined with chemotherapy. Previous research has shown chemotherapy doesn’t work as well for patients with active glucocorticoid receptors in their breast cancer tumors, Nanda said.

“By blocking the glucocorticoid receptor with mifepristone, we hope to enhance the effectiveness of chemotherapy,” she said. She’s also in the early stages of trying to determine whether this strategy works for ovarian cancer and prostate cancer.

Klimas said she chose to try mifepristone in the Gulf War illness trial because it was the safest already-approved drug that would do what she wanted it to: block the receptors to which stress hormones bind. By blocking these receptors temporarily, she said she is trying to reset the brain’s stress signals in these sick veterans. 

“We’re trying to repurpose drugs so that we can get them through to these guys fast,” she said. 

What Roe’s reversal could mean for trials

For the sake of Klimas’ research, the drug’s physical abortion effect isn’t a big concern. The Gulf War illness trial is limited to 45- to 70-year-old men. “I don’t think I’ve ever heard a patient do more than laugh about it,” she said. “Pregnancy is not one of the things male veterans worry about.” 

Medical officers run from medical transport helicopter in the Saudi Arabian Desert on Feb. 8, 1991 during during Operation Desert Storm.AP file

Even before Roe was overturned, the fraught landscape for abortion policy in the U.S. painted a more complicated picture for research like Klimas’ study.

“You can’t believe the logistical nightmares we’ve faced with this study,” she said. 

Originally, Klimas designed the trial for an outpatient clinic associated with her university hospital. But she struggled to find a research pharmacy that would work with her, a challenge she attributes to the changing policies around mifepristone. 

“We called every pharmacy in two counties and could not find one that could work with mifepristone outside a hospital setting,” she said. Ultimately, she moved the study to the Miami VA, which has an inpatient hospital research pharmacy. The red tape involved in moving the trial delayed its start by a year, after what had already been a yearlong delay due to pandemic lockdowns. 

Klimas faced these logistical challenges despite the fact that mifepristone’s makers say abortion restrictions shouldn’t impact research for other conditions. Both Danco Laboratories, which markets mifepristone for abortion under the name Mifeprex, and Corcept Therapeutics said that trial-specific protocols, which the FDA must clear, take precedence. 

Trial protocols could, in theory, differ from the rules surrounding the approved drugs, said Abigail Long, director of marketing and public affairs at Danco Laboratories. 

In other words, clinical trials investigating mifepristone for nonabortion uses aren’t subject to the FDA’s restrictions surrounding the drug when it’s used for abortion. Until recently,  that included a rule that patients seeking abortions receive mifepristone in-person from a prescriber with a special certification. During the pandemic, the FDA stopped enforcing the in-person dispensing rule, enabling patients to get the pill by mail. Then, in December 2021, the agency announced it would permanently allow the mail option. Doctors still need special certification to prescribe mifepristone, as do pharmacies dispensing it. 

Many individual states have written their own sets of laws restricting how patients can get mifepristone for abortion, though, and legal challenges loom over whether these unlawfully infringe on the FDA’s federal approval.

In a statement shortly after the Supreme Court ruling on Friday, Attorney General Merrick Garland said that states may not ban mifepristone based on disagreement with the FDA’s judgment about its safety and efficacy. 

“The Justice Department strongly disagrees with the Court’s decision,” Garland said, calling the ruling’s impact on the lives of people across the country “immediate and irreversible.”

This sets the stage for fraught legal battles in states like Kentucky and Louisiana, which enacted total bans on abortion — including medication abortion — the moment the court issued its ruling

According to Patricia Zettler, a law professor at Ohio State University who focuses on food and drug regulation, those legal challenges could now intensify with new abortion restrictions across many states. 

“There will be a lot of battles around what states can and can’t do,” she said. “The impacts that we could see in the clinical trial space will depend on how narrow or broad states attempt to restrict access to mifepristone.” Even if legal restrictions on mifepristone for abortion don’t apply to clinical trials for other uses, she said a Roe reversal could still complicate research.

“Beyond the actual legal environment, the impact on clinical trials will depend on how health care professionals and health care institutions interpret what the states are doing and how comfortable physicians and pharmacists feel in prescribing or dispensing it, even if it’s legally permissible,”  Zettler said.

Impact on multistate trials 

Klimas’ Gulf War illness study is a small, Phase 1 trial designed for just a few dozen patients at the VA location in Florida. But if the drug works, she’ll need to expand her study into Phase 2 and 3 trials, requiring many more patients enrolled across sites in multiple states. 

In a post-Roe America, where differences in abortion policies from state to state could grow even more stark than they are today, researchers could have a tough time juggling multistate trials.

“It’s bad enough with this single-site study in one state with one set of laws,” Klimas said. “But if I have to figure out all the laws in all the states that we would be using as sites, it could get more complicated.” 

Michelle Oberman, a law professor at Santa Clara University whose work centers on the effects of criminalizing abortion, sees the burden of navigating abortion landscapes across state lines as one of the more concerning ways Roe’s reversal could impact mifepristone trials.

“So does the science academy shift into red state/blue state?” she asked hypothetically. “If you want to be a serious researcher, are you going to be working in California or New York to develop new treatments?” 

A researcher with a choice of trial location would likely stick to states with the least possible abortion restrictions, she predicted. And in that scenario, patients in more restrictive states, especially those who can’t afford travel, could miss out on clinical trials. For years, travel costs have excluded marginalized populations from clinical research, making the prospect all the more troubling.

On paper, Oberman suspects mifepristone clinical trials for nonabortion use will remain legal and feasible. But in states where abortion is poised to become a crime post-Roe, she figures the downstream effects of the reversal won’t be limited to what’s technically legal. 

“It doesn’t take a prosecution to shift the way that the population feels about these meds, or the way those who would prescribe or investigate these meds think about their research,” she said. “The impulse to not get involved with the law is about to come into view. If you’re a doctor who’s both really risk-averse and incredibly driven to help your patients, you may find yourself needing to practice medicine elsewhere. Because the risks won’t be zero.”

With Roe overturned Klimas wonders if having moved the Gulf War illness trial to the VA hospital might ironically work in her favor. “This is Florida,” she said. “If it’s possible to do things to restrict abortion, it will happen here. But I’m hoping the VA move could save me.” The Department of Veterans Affairs is a federal agency, and in his statement on the ruling, Garland underscored the Department of Justice position that federal agencies and their employees answer to federal, rather than state, laws. Klimas said she’s seeking legal advice on what, if anything, Florida-specific mifepristone laws could mean for the VA hospital. 

In the meantime, she’s anxious about what this Supreme Court decision will mean, both for the many thousand already-disadvantaged women it could hurt, and for the fate of the veterans in her mifepristone trial. 

“Wouldn’t it be sad to finally find something curative for a disease you got because you served your country — that sucked out 30 years of your life — and then it got stopped because of an abortion fight?”

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