A widely used abortion medicine is in legal jeopardy, despite decades of data supporting its use.
The medicine, called mifepristone, is part of two-drug regimen that can end a pregnancy, and was used in more than half of abortions in the United States in 2020. Late last year, a group of antiabortion doctors and others sued the U.S. Food and Drug Administration, challenging mifepristone’s initial approval in 2000 and the changes the agency later made to broaden access to the drug.
In the lawsuit, they claim that the drug isn’t safe, that the FDA improperly approved it and failed to follow the science, and that mifepristone is illegal to send in the mail. The U.S. District Court judge that first heard the case sided with the group. Now, the case is being reviewed by the U.S. Fifth Circuit Court of Appeals in New Orleans; on May 17, the Fifth Circuit heard oral arguments related to the judge’s ruling. The matter may ultimately be resolved by the Supreme Court.
But the original scientific evidence used in the FDA’s approval process offered a clear answer to the drug’s safety, says Thomas Kosasa, an obstetrician gynecologist at the University of Hawaii in Honolulu who served on a 1996 committee that advised the FDA. “We made sure that it was a safe medication,” he says. “It was also effective.”
In the 23 years since the agency approved mifepristone, the drug has amassed a long track record of safety data — in the United States and around the world, says Lauren Owens, an obstetrician gynecologist at the University of Washington Medical Center in Seattle. In 2020 in the United States alone, there were nearly 500,000 medication-induced abortions, which relied on mifepristone and a second drug, misoprostol, to terminate a pregnancy. The drugs are also used to manage miscarriages. And during the coronavirus pandemic, an influx of new safety data supported what earlier studies had found.
“Millions of people have used this medication,” Owens says. She and other doctors and scientists say decades of data demonstrate mifepristone’s safety and note that the court’s decision could affect access to the drug — even in states where abortion is legal. The case comes nearly a year after the Supreme Court overturned Roe v. Wade (SN: 6/24/22).
Owens says she’s concerned that a court’s decision could potentially override medical experts. “If the FDA doesn’t get to say what medications are safe,” she says, “where does that stop?”
The FDA approved mifepristone 2000. What data did it use to decide?
On a hot day in July 1996, a group of doctors and scientists who were part of the FDA’s Reproductive Health Drugs Advisory Committee gathered in Gaithersburg, Md., to evaluate mifepristone, also known as RU-486 as well as Mifeprex. The drug had already been approved in France, England, Sweden and China. The committee’s job was to review data on the drug’s safety and efficacy for ending an early pregnancy and vote on whether to recommend its use in the United States.
Such committee meetings were typically held at the FDA’s offices in Rockville, but this time was different. This time, the committee members traveled with armed guards. Concern for their safety may have stemmed, in part, from recent violence at abortion clinics in Florida and Massachusetts, Kosasa recalls. The agency held the meeting in a small building north of Rockville; the eight committee members rode in bulletproof vehicles, police escorts leading and trailing the group.
The meeting was open to the public, but security was tight. Visitors went through metal detectors and had their bags scanned. People packed in to hear the proceedings, says committee member Diana Petitti, a physician and epidemiologist who retired from the University of Arizona College of Medicine in Phoenix in 2017. “It was totally full,” she recalls. The FDA set up an overflow room nearby for a crowd to watch the meeting on video.
FDA’s then-commissioner David Kessler opened the meeting with clear instructions for the committee: “What you need to do today is to focus on the science,” he said, according to a transcript. “Examine the clinical data carefully. Ask the tough questions and then give the FDA your best scientific advice based on the data.”
The data came from two clinical trials in France and an ongoing trial in the United States. The French trials enrolled 2,480 women, most of whom were seven weeks pregnant or less, and doctors used a dose of mifepristone followed by misoprostol two days later, if needed, to end the pregnancy. Mifepristone blocks the hormone progesterone, causing the lining of the uterus to break down. Misoprostol triggers contractions that help expel that broken-down tissue.
In the French trials, this regimen worked in about 95 percent of women, with few serious side effects, such as severe bleeding. Many women reported painful contractions, and some experienced nausea, vomiting or diarrhea. Those are expected side effects of the drugs, Petitti says. “But nothing popped out as something we really ought to be worried about.” Altogether, she says, “The safety question was pretty straightforward.”
The committee took the day to discuss mifepristone and voted 6 to 0 that the benefits exceeded the risks. Two members abstained from voting.
After multiple rounds of reviews, the FDA ultimately followed the committees’ advice and approved mifepristone in 2000, with some restrictions in place. Notably, people could take the medication up to seven weeks of pregnancy, but only under doctor supervision. And patients had to come to the office three times — once for mifepristone, once for misoprostol and then again for a follow-up visit.
Petitti says she’s surprised that mifepristone’s safety has been called into question. “I just keep waiting for somebody to show me evidence that shows something different than the evidence I saw in 1996.”
Doctors collected data on mifepristone during the coronavirus pandemic. Here’s what they found.
Since mifepristone’s approval, the FDA has eased some of its original restrictions. A 2016 update allowed for the drug’s use up to 10 weeks of pregnancy and required just one clinic visit instead of three. Then, the coronavirus pandemic spurred another change that allowed people to access mifepristone by mail, without coming into a clinic in person at all.
The FDA’s updates gave scientists a new way to investigate the safety of the drug, specifically whether past restrictions kept people safer or not. The clinic visit was one of those lifted restrictions, says Ushma Upadhyay, a public health scientist at the University of California, San Francisco.
Even without the typical pre-abortion ultrasound or pelvic exam, the medicine was about 95 percent effective at terminating a pregnancy and serious complications were rare, show data that Upadhyay and colleagues collected from February 2020 through January 2021 on nearly 4,000 people throughout the United States. The study “confirms that mifepristone is extremely safe and extremely effective,” she says.
The results echo data from other countries, including a massive study from the United Kingdom that analyzed the records of more than 18,000 telemedicine patients who had medication abortions. The drugs were 99 percent effective, and serious outcomes, such as a blood transfusion or major surgery, occurred in just 0.02 percent of people, researchers reported in 2021.
The latest data suggest that doctors can prescribe mifepristone safely, without any special exams, Upadhyay says.
That’s how prescriptions of the medication work in Canada, where mifepristone became widely available in late 2017. Canada’s drug regulators “took a really unprecedented step of treating mifepristone as any other medication,” says Laura Schummers, an epidemiologist at the University of British Columbia in Vancouver. That meant any physician or nurse practitioner can prescribe mifepristone, any pharmacy can dispense it, and patients can take the medication at home “if, when and where they choose,” she says.
Within a few years, the percent of abortions by surgery in Canada dropped from 98 percent to about 69 percent. By early 2020, more than 30 percent of first trimester abortions were provided using medication, Schummers’ team reported in the New England Journal of Medicine in 2022. The scientists also analyzed safety trends. “The take-home message was that there was no change at all to the safety outcomes,” Schummers says.
Her team’s paper adds to the stack of studies validating mifepristone’s safety. And medication abortion, she points out, is safer than childbirth, which can be deadly. As scientists reported this year, U.S. maternal deaths continue to climb (SN: 3/16/23).
In the United States, abortion is already difficult to access, Upadhyay says, especially for people of color and people with low incomes. Any decision to restrict or ban mifepristone, she says, “would be devastating for people who are most in need of care.”
In April, a Supreme Court ruling left the drug available for use while the case proceeds with the Fifth Circuit. But the appeals court decision may not be the final word; the Supreme Court could end up having the final say.
This judicial review of medication concerns not only Owens, of the University of Washington, but also Kosasa. He worries what the outcome of the case will mean for the FDA, and the agency’s ability to evaluate and approve drugs — even ones, like mifepristone, with a well-supported safety record.
If courts can go against “a whole tremendous amount of scientific evidence,” Kosasa says, “that just doesn’t seem right.”