More than half of abortions in the U.S. are medication abortions, done early in pregnancies. But less than a year after the Supreme Court overturned Roe v. Wade, federal court rulings have raised questions about the future availability of mifepristone, the first of the two-drug combination used in those abortions.
On April 7, a District Court judge suspended the Food and Drug Administration’s approval of mifepristone, which occurred 23 years ago, while another judge ruled in a separate case that the FDA couldn’t change the current availability of the drug. Less than a week later, an appeals court gave both sides part of what they wanted: The court said the FDA’s approval would remain valid, but the agency’s later changes to increase access to the drug would still be suspended while the case proceeds.
The federal government and the drugmaker have appealed that decision to the Supreme Court. The restrictions on mifepristone, as ordered by the appeals court, would take effect on April 15, unless the Supreme Court intervenes.
Here we answer questions about the court rulings, mifepristone and what may happen next.
What is mifepristone?
Mifepristone, sold under the brand name Mifeprex and also known as RU-486, is a drug approved by the FDA to terminate pregnancies through 10 weeks (70 days) of gestation. It’s the first of two medicines that are taken together as part of medication or medical abortion in the U.S.
In the FDA-approved regimen for medication abortion, one mifepristone pill is taken by mouth on the first day. Between 24 and 48 hours later, the patient places two tablets of another medicine called misoprostol in each cheek pouch, and lets them dissolve. Patients typically begin to expel pregnancy tissue two to 24 hours after taking the second drug. Patients then follow-up with their health care provider a week or two after taking mifepristone to ensure that the pregnancy has been successfully terminated.
Mifepristone ends pregnancies by blocking the hormone progesterone, which is required to maintain a pregnancy. Without the progesterone signal, the uterine lining with the implanted embryo or fetus is shed. Mifepristone also makes the uterine muscle more sensitive to prostaglandins, including misoprostol, which triggers contractions and helps open the cervix.
In some countries, misoprostol is used alone in medication abortions, but research shows the drug combo is more effective and may have fewer side effects. While FDA’s approved mifepristone regimen requires misoprostol, misoprostol is not FDA-approved for abortion, so technically it is used off-label for that purpose. Off-label prescribing, which is common, is when a doctor prescribes a drug in a different way or for a different condition than the one for which it was approved.
Outside of medication abortion, mifepristone is used off-label to help patients experiencing miscarriages or stillbirths expel pregnancy tissue and avoid procedures. The pill is also FDA-approved to treat high blood sugar in certain Cushing’s syndrome patients.
When was mifepristone approved, and how has it been regulated?
This included four phase 3 clinical trials: two in the U.S., and another two in France, where the drug was developed and was approved in 1988. It also included post-marketing safety data from numerous other countries, including France, Sweden and the U.K., all places where the drug had been in use since at least the early 1990s. An FDA document shows that at the time of approval, mifepristone was approved in 21 other countries (see page 9).
In 2000, the mifepristone approval pertained to pregnancies seven weeks along or less. Due to some safety concerns — particularly the fact that mifepristone sometimes fails, should not be given to people whose pregnancies are located outside of the uterus, and rare excessive bleeding can occur — the agency imposed several restrictions, later known as a risk evaluation and mitigation strategy, or REMS, on mifepristone.
Under the regulations at the time, the drug could not be sold in pharmacies or online, and instead was supplied directly to doctors meeting certain qualifications, including being able to accurately date pregnancies, diagnose ectopic pregnancies, and having the ability to perform or arrange for any necessary surgery. Certified doctors, who gave mifepristone to patients in person, also had to provide a “medication guide” to patients and agree to report any adverse events to the drugmaker.
Over the years, the FDA continued to monitor the safety and efficacy of mifepristone and made slight modifications to the required restrictions. Most notably, in 2016, the agency extended approval to pregnancies up through 10 weeks of gestation, allowed health care providers other than physicians to become certified to provide mifepristone, and reduced the required office visits for patients from three to one. Given 15 years of safety data showing “the known serious risks occur rarely” — and no sign of new safety concerns — the agency also dropped the requirement that providers report all adverse events, requiring only deaths to be reported.
In April 2019, the FDA approved a generic of Mifeprex.
During the COVID-19 pandemic, the FDA did not enforce the in-person dispensing requirement, allowing mifepristone to be mailed to patients. In 2023, after reviewing the evidence, the agency dropped the in-person requirement from the REMS program altogether and added a requirement that any pharmacies that offer the drug be certified.
Current REMS regulations therefore require that a certified health care provider prescribe mifepristone, but that person does not need to be a physician, nor does the pill need to be given to the patient by that provider. Instead, mifepristone can be mailed to patients by certified pharmacies. Patients still must be given a medication guide and health care providers must inform patients of the risks of using mifepristone.
On its website, the FDA notes that the agency has never “removed a drug with a REMS from the market due to new or serious issues that could not be mitigated by the REMS.”
Today, mifepristone is approved in about 80 other countries, according to the FDA.
Where did this lawsuit challenging the FDA approval begin?
A group of four anti-abortion organizations and four physicians filed a lawsuit — Alliance for Hippocratic Medicine v. U.S. Food and Drug Administration — in November 2022 in the U.S. District Court for the Northern District of Texas. That was five months after the Supreme Court overturned Roe in a 5-4 ruling that said the “Constitution does not confer a right to abortion … and the authority to regulate abortion is returned to the people and their elected representatives.” The plaintiffs challenged the FDA’s approval in 2000 of mifepristone and subsequent REMS modifications to how the drug can be prescribed and dispensed.
On April 7, Judge Matthew J. Kacsmaryk, an appointee of former President Donald Trump, sided with the plaintiffs’ arguments, ordering a “stay,” or suspension, of the approval and subsequent actions related to it.
Legal experts have said this is the first time a judge has gone against FDA objections and overruled a drug it has approved. “Plaintiffs have pointed to no case, and the government has been unable to locate any example, where a court has second-guessed FDA’s safety and efficacy determination,” the federal government said in a January 2023 brief.
The federal court’s order is a preliminary injunction, which is issued before a trial and final judgment in the case if the plaintiffs show they are likely to succeed in the lawsuit on its merits and there’s a threat of “irreparable harm” without the injunction, among other factors.
Kacsmaryk delayed his order for seven days to allow time for an appeal to the 5th U.S. Circuit Court of Appeals, which the federal government and Danco Laboratories, a manufacturer of mifepristone and also a defendant in the case, promptly filed.
What about the other, conflicting District Court ruling?
In February, Democratic attorneys general filed suit, also against the FDA, saying the agency should remove restrictions on who can prescribe and dispense mifepristone. On the same day as the Texas court ruling, District Court Judge Thomas O. Rice in the Eastern District of Washington granted a preliminary injunction barring the FDA from “altering the status quo and rights as it relates to the availability of Mifepristone” in the 17 states, plus the District of Columbia, of the plaintiffs.
The ruling by Rice, an appointee of former President Barack Obama, doesn’t change the FDA’s restrictions under REMS. The plaintiffs argue these “burdensome restrictions” on a drug that has been administered for more than 20 years “with only ‘exceedingly rare’ adverse events” have “no basis in science. It only serves to make mifepristone harder for doctors to prescribe, harder for pharmacies to fill, harder for patients to access, and more burdensome for the Plaintiff States and their health care providers to dispense.”
In addition to D.C., the states are: Washington, Oregon, Arizona, Colorado, Connecticut, Delaware, Illinois, Michigan, Nevada, New Mexico, Rhode Island, Vermont, Hawaii, Maine, Maryland, Minnesota and Pennsylvania. Abortion is legal in all of those states.
Rice later confirmed that the rulings in the Texas case, including from the appeals court, had no bearing on his order pertaining to those states.
What did the appeals court say?
On April 12, the 5th Circuit overruled part of Kacsmaryk’s injunction. The three-judge panel — two appointed by Trump and one by former president George W. Bush — said the anti-abortion groups had waited too long to file suit against the FDA’s 2000 approval of mifepristone, so that couldn’t be suspended. The challenge was beyond the statute of limitations. But the appeals court ruled that the agency’s subsequent actions on the drug could still be challenged and would be suspended under Kacsmaryk’s order while the case proceeded.
As we explained, those subsequent actions include allowing distribution to patients via mail and the FDA’s 2016 REMS that allowed mifepristone to be prescribed up to 10 weeks of gestation rather than seven weeks and permitted health care providers who aren’t doctors, such as nurse practitioners, to prescribe it.
The 5th Circuit ruling is temporary as the appeal proceeds. The court set oral arguments for May 17.
What are some of the legal arguments in the case against mifepristone?
There are many legal claims in this case, but David S. Cohen, a professor of law at Drexel University and an expert in legal issues concerning abortion, explained to us that there were three main claims in Kacsmaryk’s April 7 ruling in the District Court: that mifepristone isn’t safe, that the FDA incorrectly used a regulation in approving it, and that the FDA violated an 1873 law that would ban the mailing of the drug. On all three, the judge sided with the plaintiffs over the FDA.
The FDA approval process requires drugmakers to demonstrate safety and effectiveness through clinical trials, and after a drug is approved, the agency continues to monitor its use. In its brief, the FDA said its 2000 approval “rested on a comprehensive evaluation of the scientific data,” that subsequent evidence “confirms that mifepristone has been demonstrably safe and effective in practice, when considered based on clinicians’ real-world experience prescribing the medication,” and that serious adverse events “are rare,” according to the agency’s review of the scientific literature.
We’ll have more about mifepristone’s safety below.
Kacsmaryk, though, wrote that “[c]ompelling evidence suggests” the FDA’s statistics on adverse events “understate the negative impact the chemical abortion regimen has on women and girls,” using terminology for the two-drug regimen preferred by anti-abortion advocates. (The judge also repeatedly referred to a fetus or embryo as an “unborn human.”)
Among the evidence offered by the plaintiffs on mifepristone’s safety is a 2021 study that we’ve written about before on emergency room visits by Medicaid patients authored by Charlotte Lozier Institute, an anti-abortion group. Kacsmaryk cited it in his ruling, saying that medication abortions “are over fifty percent more likely than surgical abortion to result in an emergency room visit within thirty days.” But as we’ve explained, the higher rate of visits doesn’t equate to a higher safety risk. Other research shows most ER visits by women with Medicaid, who may not have a primary care doctor, after a medication abortion weren’t for serious complications.
Kacsmaryk also argued that medication abortion is harmful to women’s mental health. He cited a study, co-authored by a researcher with Charlotte Lozier Institute, that analyzed 98 anonymous blog posts from women who had medication abortions and visited a website called “Abortion Changes You.” Many of the women who submitted a post regretted their abortions.
But submissions to such a website are unlikely to be representative of the experience of most people. Moreover, other research, including the most rigorous work, has not found that abortion causes mental health problems such as depression, anxiety or suicidal thoughts, or leads to drug use, as some have proposed. The best studies compare outcomes in people who had abortions with those who were denied an abortion. One such study, known as the Turnaway Study, not only found no increase in mental health issues in those who had abortions, but found that those who were denied an abortion were more likely to suffer anxiety and have low self-esteem in the short term, experience poor physical health, and to fall below the federal poverty level, among other negative outcomes.
On the FDA regulation point, the judge said the FDA erred in using a regulation called Subpart H in approving mifepristone. Subpart H allows for approval of new drugs that “have been studied for their safety and effectiveness in treating serious or life-threatening illnesses and that provide meaningful therapeutic benefit to patients over existing treatments.” It also allows the FDA to impose restricted distribution requirements, as a Government Accountability Office report on mifepristone’s approval explains.
It took more than four years for the FDA to approve the drug after the drug sponsor submitted its application.
Kacsmaryk agreed with the plaintiffs that this regulation shouldn’t apply in this case because pregnancy isn’t an “illness” but rather “a normal physiological state most women experience.”
The FDA said that neither the agency nor Congress had adhered to that narrow interpretation. The FDA said the regulation applies to drugs used for serious “conditions,” as explained in its final rule. Congress later “ratified FDA’s understanding of its regulation” by using the language “disease or condition” in a law pertaining to the REMS framework.
Finally, Kacsmaryk said the plaintiffs are likely to succeed in an argument that the FDA violated the 1873 Comstock Act by allowing the distribution of mifepristone via the mail, as it first did during the coronavirus pandemic in 2021. The judge wrote that the law prohibits mailing anything that would produce an abortion. The FDA argued that misconstrues the law — which was known as a “chastity” law and originally prohibited mailing birth control as well as any “obscene, lewd or lascivious” publications.
“As the Department of Justice’s Office of Legal Counsel has explained, however, since the early 20th century the Comstock Act has been understood ‘not to prohibit all mailing or other conveyance of items that can be used to prevent or terminate pregnancy,’” the FDA said in its brief.
The FDA sought to have the suit tossed out, arguing that the plaintiffs didn’t have standing. In order to sue in federal court, a plaintiff must show “standing,” meaning that they have been harmed, the defendant caused that harm and a ruling by the court could remedy the harm. Both the circuit court panel and district judge have ruled that the plaintiffs do have legal standing, although a number of legal scholars have questioned this.
What more did the appeals court say about these arguments?
On the Comstock Act, the appeals court said it couldn’t fully explore how and whether the law should apply given the speed of the District Court’s ruling. But the judges wrote that the “uncertainty” over the law’s applicability “favors the plaintiffs” because the defendants had the burden of proving their arguments to get the court to overturn the lower court’s injunction.
“Our decision to grant partial relief does not reflect our view on any merits question,” the judges wrote. But they did say the plaintiffs were “unlikely” to fail in claiming the FDA, in its 2016 and subsequent REMS changes, violated an “arbitrary-and-capricious standard” it must meet under the Administrative Procedure Act. The APA lays out how federal agencies can make rules and how the courts can review them. Under the arbitrary-and-capricious standard, agencies “must examine the relevant data and articulate a satisfactory explanation for its action including a rational connection between the facts found and the choice made,” the judges wrote, citing prior court rulings.
The appeals court did not delve into the meaning of “illnesses” in Subpart H.
As for the court’s decision not to also overturn the District Court’s stay on the FDA’s 2016 and later changes, the judges wrote that the government and Danco didn’t show how there would be “irreparable harm” from leaving that suspension in place.
How safe and effective is mifepristone?
Numerous studies have demonstrated that mifepristone is safe and effective for terminating early pregnancies.
According to mifepristone’s prescribing information, 22 clinical trials, including seven in the U.S., have evaluated mifepristone when used with misoprostol at 10 weeks or less of gestation. The results show patients on average have a complete medical abortion at least 96.2% of the time, meaning the drug fails in less than 4% of cases.
The failure rate is even lower — below 2% — for pregnancies terminated at seven weeks or less, although it increases to less than 7% during the 10th week of gestation.
Medication abortion with mifepristone is also safe. While most patients experience side effects, including nausea, weakness and fever, serious ones are rare. Ten clinical trials, according to the prescribing information, found that a serious adverse reaction, such as a blood transfusion or serious infection, affects fewer than 0.5% of people.
Many other studies have borne this out, finding serious adverse events are typically below 1%, and often well below. As we’ve written before, a 2015 paper published in Obstetrics & Gynecology reviewed 20 other studies that collectively included more than 30,000 patients, and found that “[s]evere adverse events like blood transfusion (0.03–0.6%) and hospitalization (0.04–0.9%) are uncommon” (one co-author of that paper reported being a consultant for Danco).
Cramping and bleeding — heavier than a normal period — are expected with medication abortion. The main concern is excessive bleeding, which can be dangerous and could indicate that the medications failed and the individual needs to complete the abortion with a procedure. Another concern is infection, which could lead in rare cases to sepsis.
It’s important to note that not all people are good candidates for medication abortion, as the drugs should not be used in people with ectopic pregnancies, those using an IUD, or in people with certain health conditions or those taking certain medications.
Death is exceedingly rare. Through June 2022, the FDA received 28 reports of deaths out of the approximately 5.6 million people who took mifepristone since its approval. Reported deaths do not necessarily mean the death was caused by medication abortion; a number of the deaths were from causes that do not have any link to the medication, including suicide, homicide or suspected homicide, and drug abuse. Two deaths were due to ectopic pregnancies, while nine were for sepsis. Eight of the nine sepsis cases involved vaginal use of misoprostol, which is not part of the FDA-approved regimen for medication abortion.
Death after medication abortion is so rare that it’s difficult to determine an accurate death rate, but one U.S. study suggests it is around 1 per 100,000 people. This is similar to the overall abortion death rate and significantly lower than the risk of dying from childbirth.
Compared with an abortion procedure, medication abortion is less effective, but the difference is small (procedural abortion is commonly referred to as surgical abortion, even though no there is no incision).
Some studies suggest that compared with an abortion procedure, medication abortion is associated with a higher rate of adverse events, although the differences are usually small or primarily apply to side effects that are not serious.
One 2015 paper, analyzing outcomes from more than 50,000 Medicaid patients in California, found that major complications occurred in 0.31% of medication abortions versus 0.16% in procedural abortions.
A study from Finland, cited in Kacsmaryk’s ruling, found that total adverse events were nearly four times higher in medication abortions compared with abortion procedures. But that was just one finding from the study, which concluded by saying, “termination of pregnancy by means of either medical or surgical methods is associated with a low level of serious complications.”
Dr. Oskari Heikinheimo, a professor of obstetrics and gynecology at the University of Helsinki who was the senior author of the paper, told us that “[s]erious complications or serious adverse events were rare and similar after medical or surgical abortion.”
The higher rate of total adverse events, he said, was driven by concerns women had about uterine bleeding. Because a procedural abortion removes the pregnancy tissue, while a medication abortion does not, people experience more bleeding with mifepristone, even if it’s not harmful.
Another contributing factor, Heikinheimo said, is that abortion is a public health service in Finland, so “women had a low threshold of attending medical care, without significant expenses to them and no need to travel long distances.” He also noted that the study was performed when medication abortion was new to Finland. As with the U.S., medication abortion was introduced there in 2000, and the study covered 2000 to 2006.
Far from thinking his study means medication abortion is unsafe, Heikinheimo said medication abortion has an “impressive safety” record, “even if provided via telemedicine.” He cited a U.K. study that found no safety or effectiveness concerns with providing medication abortions without an in-person visit or ultrasound.
Thus, while there are differences between mediation abortion and an abortion procedure that patients should consider, the medical consensus is that both options are safe and effective.
Indeed, a 2018 review from the National Academies of Sciences, Engineering, and Medicine found that “clinical evidence clearly shows” that all methods of legal abortion in the U.S., including medication abortions, “are safe and effective” and that “[s]erious complications are rare.”
What happens next legally?
The circuit court had set a date of May 17 to hear oral arguments in its review of the District Court’s injunction, but whether that happens is subject to what the Supreme Court does.
Eventually, the case would be heard on its merits in the District Court in Texas. And that court’s final judgment would likely be appealed to the circuit court and ultimately to the Supreme Court. That process could take a couple of years.
What can the FDA do as the cases move forward?
Cohen, the law professor at Drexel, told us the FDA could — and should — use its enforcement discretion, meaning it can say it isn’t going to enforce particular violations. Cohen equated the concept to law enforcement not having the resources to pull over everyone who drives 65 miles per hour in a 55 speed-limit zone, so they have to prioritize their resources.
“Law enforcement agencies are always using enforcement discretion … to say we’re going to go after the offenses that really matter,” he said in a phone interview. Similarly with unapproved drugs, the FDA focuses its efforts on drugs that aren’t effective or safe.
With mifepristone, the FDA could issue a notice saying it is using its enforcement discretion to not enforce the old requirements.
This is how the FDA initially allowed mifepristone to be distributed to patients through the mail during the COVID-19 pandemic, when there was concern about in-person office visits.
We spoke with Cohen before the appeals court ruling, but he said in Twitter posts after that decision that this concept still applies.
Another option would be for the FDA to expedite a new application for mifepristone, he told us, but that’s a lengthy process.
Will mifepristone be available despite the court rulings so far?
Yes, in states where abortion is legal. (Thirteen states have outlawed abortion, according to the New York Times’ tracking of such laws.) The appeals court said the FDA’s 2000 approval could stand, so the drug remains on the market as an FDA-approved medication.
Barring an enforcement discretion notice from the FDA, as Cohen and others advocate, whether some of the pre-2016 restrictions on mifepristone will be followed could depend on the health care provider. Under the appeals court ruling, providers could prescribe mifepristone off-label beyond the seven weeks’ gestation and eliminate extra office visits, Cohen said in a tweet.
“Getting around the in person requirement is trickier,” Cohen said.
Greer Donley, a law professor at the University of Pittsburgh and a signatory of an amicus brief in the Texas case, said on Twitter that some telehealth “would still be allowed,” such as a telehealth appointment between a doctor in a big city and a patient who would pick up the medication from “satellite offices in smaller towns.”
And there are the 17 states, plus D.C., that are still under the Washington District Court order. The 5th Circuit’s ruling “should not impact anything in the 17 states + DC that are protected by the WA order unless SCOTUS says otherwise,” Donley said in another Twitter thread.
But in the other 33 states, “returning to the pre-2016 REMS will be a big deal,” she said. “In-person dispensing would shut down virtual clinics & overwhelm brick-&-mortar clinics. Abortion would be harder to access, less private & more expensive. Only doctors could prescribe.”
And the Comstock Act language in the appeals court ruling raises the possibility of criminal action against those who ship the pills, at least in a future Republican administration.
Even if the FDA doesn’t issue a statement saying it won’t enforcement the pre-2016 requirements, some providers “may decide that practically, the FDA is unlikely to target them under [President Joe] Biden,” Donley said.
Also, as the cases move forward, if patients can’t get mifepristone, medication abortion can continue by using only misoprostol, which is the protocol used in some other countries.
There are no lawsuits against misoprostol, Cohen said, and they would be difficult to pursue. The drug is FDA-approved to reduce stomach ulcers.
In addition, a group called Aid Access operates abroad and ships medication abortion pills from pharmacies in India to patients in the United States.
Are there broader implications if a court ultimately overrules an FDA approval?
The pharmaceutical industry and experts in health law have said that a court overruling the FDA approval of a drug would have repercussions beyond the abortion debate, potentially sparking lawsuits challenging other FDA-approved treatments and vaccines.
“If successful, this case could invite copycat lawsuits to limit other forms of politicized health care,” Donley, of the University of Pittsburgh, and Rachel Sachs, a law professor at Washington University in St. Louis and an expert in food and drug regulation, wrote in the Washington Post in early March. “Potentially at risk would be medications for a much larger range of indications,” they said.
Such a ruling also could affect research and investments in new drugs. “It could chill innovation nationwide,” Donley and Sachs said. “Manufacturers might become wary of investing time and money into products for a wide range of conditions which may — decades down the line — be the subject of nuisance litigation.”
More than 700 pharmaceutical and biotech industry executives and leaders expressed the same concern in a letter condemning Kacsmaryk’s April 7 ruling. “The decision ignores decades of scientific evidence and legal precedent,” they wrote. “Adding regulatory uncertainty to the already inherently risky work of discovering and developing new medicines will likely have the effect of reducing incentives for investment, endangering the innovation that characterizes our industry.”
“If courts can overturn drug approvals without regard for science or evidence, or for the complexity required to fully vet the safety and efficacy of new drugs, any medicine is at risk for the same outcome as mifepristone,” said the letter’s signatories, which included the CEOs of Pfizer and Biogen and leaders of Merck, Bayer and Bristol Myers Squibb.
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