FDA Pulls Drug Intended to Prevent Preterm Births From the Market

The Food and Drug Administration (FDA) is pulling a drug aimed at preventing preterm births from the market. The move comes after a key advisory committee found the drug to be ineffective. But this decision does not come without some controversy.

In October 2022, the FDA held a hearing about a drug produced by Swiss pharmaceutical company Covis, called Makena. The FDA's Obstetrics, Reproductive, and Urologic Drugs Advisory Committee heard testimony surrounding the medication. Ultimately, the members recommended withdrawing Makena from the market.

By early April 2023, the FDA's commissioner and chief scientist issued their final decision to withdraw Makena's approval under the accelerated approval pathway.

“It is tragic that the scientific research and medical communities have not yet found a treatment shown to be effective in preventing preterm birth and improving neonatal outcomes—particularly in light of the fact that this serious condition has a disparate impact on communities of color, especially Black women,” FDA Commissioner Robert M. Califf, M.D. says in a news release. “Fundamentally, however, the touchstone of FDA drug approval is a favorable benefit-risk assessment; without that favorable assessment, the drug should not have the status of being FDA-approved.”

Critics argue Makena's removal from the marketplace will negatively impact high-risk populations and deepen health inequalities. This has the potential to change the landscape ofobstetric medicine.

What is the Drug Makena Used For?

Makena is an injectable drug meant to preventpreterm laborof singleton babies in a second pregnancy. It was initially fast-tracked through approval in 2011 by the Center for Drug Evaluation and Research (CDER), an arm of the FDA. The FDA accelerated its approval in order to get it to the market quicker. Officials noted that Makena was being used to treat a serious condition, and at the time, it provided an advantage over other treatments.

Why was Makena Removed From the Market?

In a nutshell, the FDA says Makena is not effective and the benefits don't outweigh the risks. Makena's initial approval hinged on a study conducted in 2011. That trial suggested the drug reduced preterm labor in people who had a previous unexplained preterm birth. As a condition of the fast-tracked approval, Covis Pharma had to move forward with clinical trials to confirm that finding. The company also had to show it also improved the health of babies born to people who had a previous preterm birth.

In their last international trial, the FDA found that Makena's effectiveness was lower than expected. It did not show improvement in the health of those children born to parents who were treated with the drug.Further, the trial did not demonstrate Makena's effectiveness to reduce preterm birth at all.

"The committee found that the body of current evidence did not support continuing the accelerated approval of Makena for the prevention of recurrent preterm birth in anyone with a history of a prior spontaneous preterm birth between 20 and 37 weeks," saysAnjali Kaimal, MD, a maternal-fetal specialist who was invited by the FDA committee to testify hearing.

Because of conflicting information over the effectiveness of the drug, the FDA panel proposed to withdraw Makena from the market, as well as its generic equivalents.The FDA adopted that recommendation a few months later.

"Obstetric literature suggests that spontaneous preterm birth likely has many causes, so it may be that some people could benefit from Makena, but the evidence to this point does not clearly indicate who that population is. The consensus was that additional research was needed," Dr. Kaimal says.

How Does Removing Makena Affect Pregnant People?

With Makena's removal, there now is no medication on the market to treat preterm births.

"There are very few FDA-approved medications for any pregnancy complications. This reflects the fact that pregnant people are an understudied population," Dr. Kaimal says. "Not having products on the market does not mean that there are no evidence-based interventions for the treatment of pregnant people. Our professional societies provide guidance regarding evidence-based practices."

Dr. Kaimal cited groups like theAmerican College of Obstetricians and Gynecologistsand theSociety for Maternal-Fetal Medicineto help guide the treatment of pregnant people.

Covis Pharma fought for its product initially. "As presented during the hearing, we believe that Makena is effective in a higher-risk patient population," Raghav Chari, PhD, chief innovation officer at Covis Pharma says in a statement.

In the initial accelerated study to gain Makena's market approval in the United States, the majority of responders were people of color withhigh-risk pregnancies. However, the committee's subsequent trial did not indicate a higher efficacy for people of color over any other targeted demographic.With the removal of Makena from the market,BIPOC familiesmay find themselves without support, especially if no other medication is developed.

“我们承认the outset the serious problems of preterm birth with respect to both maternal and neonatal health and the contribution of institutional forces that have led to health disparities, including preterm birth, among Black women,” says FDA chief scientist Namandjé Bumpus, Ph.D. in the news release. “Nothing in this opinion is intended to minimize these concerns – to the contrary, our hope is that this decision will help galvanize further research.”

Covis Pharma's stance on the medication as beneficial for high-risk patient populations while pointing to their initial study is controversial. Critics are pushing back on the company using its own study in an effort to keep the medication on the market.

"Black birthing people experience a high rate of spontaneous preterm birth in addition to other maternal and neonatal morbidity and mortality, but offering a medication not shown to be effective is not going to help to solve that concern," Dr. Kaimal explains. "[It] may be a barrier to investigating other potentially effective interventions."

What's Next for Makena?

With the FDA deciding to withdraw Makena from the market, the drug and its generics are not allowed to be sold. But officials say they recognize there is a supply of the medication already distributed. If you have any questions about the medication or if you have it in your possession, please contact your healthcare provider.

About a month before the FDA's final decision, Covis Pharma announced it "respects" the recommendation of the FDA panel. The drugmaker announced a plan to voluntarily pull Makena and begin a "wind-down period" for those patients who were currently in the process of treatment. The FDA rejected that plan, saying the withdrawal needed to happen immediately.