FDA pushes to withdraw pregnancy drug, society pushes back

WASHINGTON (AP) — The maker of America’s only drug to prevent preterm birth is making a last-ditch effort this week to keep its drug on the market, even as health regulators insist it doesn’t work.

A Food and Drug Administration meeting that opened on Monday comes more than two years after the agency declared the drug ineffective and called for its withdrawal. Drugmaker Covis Pharma challenged the agency’s finding, holding a highly unusual three-day public hearing.

The meeting points to the limits of the FDA’s authority and the lengthy and onerous process for withdrawing a drug in the rare cases when a company does not voluntarily do so at the agency’s request.

The hearing will resemble a courtroom trial, with FDA staff and company scientists presenting arguments for and against the drug Makena, followed by a vote on Wednesday by a panel of outside experts. FDA officials will ultimately make the final decision on whether or not to order a withdrawal.

About 10% of births in the United States occur too early – before 37 weeks, which increases the risk of serious health problems and even death in infants. Complicating Makena’s debate is the backing of America’s leading obstetrics group to keep the decade-old drug available while more research is done.

“The need for effective treatment for preterm birth is great,” says the American College of Obstetricians and Gynecologists. “Makena and its associated generics represent the only treatment currently available to obstetrician-gynecologists to help prevent this condition.”

But the FDA says existing data shows that weekly injections of the drug do not help prevent repeated preterm birth.

“Based on the evidence presented today, Makena has not been shown to be effective,” FDA chief drug officer Dr. Patrizia Cavazzoni said in her opening remarks Monday. “Its risk and benefit profile is unfavorable and it should be taken off the market.”

The dispute is likely to increase scrutiny of the agency’s so-called fast-track approval program, which allows drugs like Makena to be launched based on promising early results, while additional studies, usually more important, are carried out.

“Makena is used as an example of the many different critiques of this program,” said Rachel Sachs, a food and drug law scholar at Washington University in St. Louis. “It may not be fair to other drugs, other diseases, other patient groups, but we are forced to respond to the situation this presents.”

At best, the Accelerated Approval Program is credited with accelerating the availability of breakthrough therapies for HIV and cancer. But over the past decade, the FDA has come under increasing criticism for failing to track fast-track drugs with incomplete or unconvincing confirmatory data, including a slew of expensive cancer drugs on the market.

In recent years, the FDA’s cancer division has begun urging companies to stop selling their drugs for uses granted under these so-called “pending approvals.”

The FDA approved Makena in 2011 based on a small study suggesting it reduced preterm birth rates in women with a history of early deliveries. Makena is a synthetic version of the hormone progesterone, which helps the uterus grow and sustain a pregnancy. Women can start injections after 16 weeks of pregnancy.

The accelerated approval was granted on the condition that Makena’s original developer, Hologic, conduct a follow-up study confirming that the drug led to lower rates of disability and death in newborns.

But the results of an international study of 1,700 women published in 2019 showed that the drug did not reduce premature births – as originally thought – or lead to better outcomes for babies, while increasing the risk of blood clots, depression and other side effects in mothers.

In briefing papers released this month, the FDA said leaving Makena on the market “results in false hope, risks associated with treatment, and other burdens” like excessive medical expenses. According to a recent federal report, the United States has spent $700 million on Makena since 2018 through various government programs, such as Medicaid and Veterans Affairs.

The FDA advisory also applies to several generic versions of the vaccine.

Drugmaker Covis argues that Makena is effective, and flaws in the 2019 study obscured its benefits. The Luxembourg-based company points out that black women are at a higher risk of preterm delivery, but accounted for just 7% of women in the international study, compared to 59% in the original US study used for endorsement. He wants time to do another study in high-risk patients, especially black Americans.

A patient group created with Covis funding, the Preterm Birth Prevention Alliance, made similar arguments in letters to the FDA.

“We believe there is no valid public health reason to deny” patients and physicians access to Makena, the company said in an emailed statement.


Follow Matthew Perrone on Twitter: @AP_FDAwriter


The Associated Press Health and Science Department is supported by the Howard Hughes Medical Institute Department of Science Education. The AP is solely responsible for all content.