Why the Mifepristone Case Matters So Much: A Safe and Effective Drug is Being Reviewed by the Federal Courts

Mifepristone is one of a pair of medications commonly used to induce elective abortion. Recently, in response to a lawsuit brought by a group of anti-abortion doctors and medical groups, a federal court judge in Texas decided that the U.S. Food and Drug Administration (FDA) erred in its approval of the drug for medical abortion 20 years ago and ordered it off the market. An appeals court and then the U.S. Supreme Court stayed that order so that mifepristone is now still available. The Supreme Court ordered a lower court to review the original judge’s decision, which, as of this writing, was scheduled to occur last month. We do not know when that court will issue its decision, which  could take at least a year. So, for now, in states where abortion remains legal after the Dobbs decision, doctors can still prescribe mifepristone.

There are at least three reasons why the federal court decision that ruled against mifepristone is troubling. First, a  majority of abortions in the U.S. are now accomplished with medication rather than surgical interventions, so that banning mifepristone would make an important, safe, and effective approach to elective abortion unavailable. Second, mifepristone is also prescribed by doctors for purposes besides medical abortion and banning the drug would make some important therapeutic options disappear. Finally, the court decision has the potential for setting a dangerous precedent for judicial interference with the work of the FDA. Let’s look at each of these potential and troubling issues.

Medical Abortion is Safe and Effective

One of the main biological actions of mifepristone is to block the receptor for the naturally occurring hormone progesterone. This means that progesterone cannot bind to its target receptor on the uterus during pregnancy, causing the lining of the uterus to break down. This makes the pregnancy unable to continue. Mifepristone is approved for use by the FDA up to 70 days after the last menstrual period. Typically, a second drug, misoprostol, is then taken up to 48 hours later. Misoprostol causes the uterus to empty. This method of medical abortion is reported to be between 95% and 99% effective at terminating a pregnancy. It is also very safe: adverse side effects and complications from medical abortions using mifepristone are uncommon.  According to the FDA:

The FDA approved Mifeprex [a brand name for mifepristone] more than 20 years ago based on a thorough and comprehensive review of the scientific evidence presented and determined that it was safe and effective for its indicated use…The FDA’s periodic reviews of the postmarketing data for Mifeprex and its approved generic have not identified any new safety concerns with the use of mifepristone for medical termination of pregnancy through 70 days gestation.

Thus, any attempt to impugn the safety and effectiveness of mifepristone for medical abortion has no scientific basis. Banning mifepristone would remove an important option for pregnant people who decide to terminate a pregnancy during the first 10 weeks. In fact, a  recent Pew survey found that by more than two-to-one, Americans believe that medication abortion should be available in their state.

Mifepristone Has Multiple Uses

Mifepristone has other uses besides elective pregnancy termination. In addition to its effect of blocking progesterone, mifepristone also blocks another hormone receptor called the glucocorticoid receptor. This action is the basis of its FDA-approved use to treat elevated glucose levels in patients with a condition called Cushing’s syndrome, which involves abnormally high levels of the hormone cortisol.

It is important to remember that the FDA regulates drugs and drug companies, not medical practice. When a drug is approved for one purpose (also called an “indication”), studies may show it to be safe and effective for other indications. Even without formal FDA approval, physicians are free to prescribe medications for unapproved indications if scientifically justified. An example is the use of mifepristone to treat a type of  uterine tumor called leiomyoma. Mifepristone is also an important part of the treatment of  miscarriages. About one in five pregnancies end in a miscarriage, usually before 12 weeks. If the miscarriage is retained in the uterus, it is important to expel it to prevent serious complications. Mifepristone softens and dilates the uterine cervix, preparing the way to then administer misoprostol or use surgical procedures to remove the miscarried fetus.

Banning mifepristone would therefore make the drug unavailable to treat all these medical issues. Years of medical research and experience would be instantly negated by such a move.

The FDA Process Would Be Jeopardized

The FDA has honed its methods and procedures for deciding whether to approve a new medication or medical device over decades. That process is sometimes subject to legitimate criticism because it can be slow and cumbersome in some cases or, as in the case of the recently approved Alzheimer’s disease drug Aduhelm, premature. For the most part, however, the FDA has developed a process that is effective at protecting the public from dangerous medications and making safe and beneficial ones available. Mistakes have been fortunately very uncommon. In general, the FDA is considered the global gold-standard for evaluating drug safety and efficacy. 

In the case of mifepristone, it is clear that the FDA followed its usual careful and methodical procedures in reviewing the data submitted from clinical trials by the drug’s original manufacturer. In an editorial in the journal  Science, former FDA commissioner Margaret Hamburg and former FDA principal deputy commissioner Joshua Sharfstein described the process FDA used to review the mifepristone application as follows:

The agency’s review of mifepristone in 2000 was thorough and fair. The drug’s manufacturer submitted a large dataset for the agency’s experts to review. An external advisory panel supported its approval. After a 6-month review, FDA’s scientific staff concluded that mifepristone is safe and effective. Over the past two decades, the medication’s safety record has grown stronger, with major medical professional associations in full support of access. Over time, the FDA, after thorough safety reviews, loosened restrictions on distribution. 

Twenty-three years since mifepristone’s first approval, no new serious adverse events have been observed, reinforcing that the FDA’s original decision to approve mifepristone, based on the drug’s safety and effectiveness, was scientifically and procedurally correct.

The decision to overturn the FDA’s approval of mifepristone stands as a potential challenge to the system we have come to rely on to ensure that new drugs are safe and effective. Legal scholar Christine Coughlin points out that the FDA is the government’s oldest consumer protection agency and  wrote in discussing the judge’s decision that “The FDA needs to be able to use its scientific expertise to make data-driven decisions that balance safety and access, without the ability of a single judge to potentially gut the system.”

Although the judge who issued the ruling ordering mifepristone off the market claimed to be basing the decision on a review of the evidence and of the FDA’s procedures, it is clear that in fact the decision was not scientifically based but rather ideological. That makes it an improper intrusion on the health of pregnant people and on established medical practice and a threat to the orderly process of drug development and approval. The FDA is not in the business of making drug approval decisions based on moral or religious arguments; the data were clear in 2000 and remain clear today that mifepristone is safe and effective as a medication for abortion.

The judge’s decision therefore stands to wreak havoc on the drug approval process if it allows anti-science groups an inroad to using the courts to challenge scientific conclusions. Our fear is that anti-vaccine groups will be emboldened to use the federal judge’s ruling to launch legal challenges against the many safe and effective vaccines we now have. Similarly, anti-psychiatry groups could challenge approvals of psychiatric drugs like antidepressants and wellness groups might even sue the FDA to get any number of medications they believe they have alternatives to banned.

We hope further judicial review will recognize that mifepristone was properly approved in 2000, that other actions the FDA has since taken to lift restrictions it had imposed back then on access to mifepristone were similarly in keeping with appropriate scientific and medical procedures, and that the courts should be extremely careful when second–guessing the careful work the agency performs.