The maker of America’s only drug designed to prevent premature births is making a last-ditch effort this week to keep its drug on the market despite health regulators insisting it doesn’t work.
A Food and Drug Administration meeting that began Monday comes more than two years after the agency declared the drug ineffective and called for it to be phased out. Drugmaker Covis Pharma contested the agency’s conclusion, holding the highly unusual three-day public hearing.
The meeting underscored the limits of the FDA’s authority and the long, arduous process of delisting a drug in the rare cases when a company does not want to do so voluntarily at the agency’s request.
The hearing will resemble a courtroom trial, with FDA staff and company scientists presenting arguments for and against the Makena drug, followed by a vote Wednesday by a panel of outside experts. FDA leaders will ultimately make the final decision on whether to order a recall.
About 10 percent of births in the U.S. come too early — before 37 weeks, raising the risk of serious health problems and even death in babies. The debate over Makena is complicated by support from America’s leading obstetrics group to keep the decades-old drug until more research is done.
“The need for effective treatment of preterm birth is great,” says the American College of Obstetricians and Gynecologists. “Makena and related generics represent the only treatment currently available to OB-GYNs to help prevent this condition.”
But the FDA says existing data show that weekly injections of the drug do not help prevent recurrent preterm birth.
“Based on the evidence shown today, Makena has not been shown to be effective,” the FDA’s chief drug officer, Dr. Patrizia Cavazzoni, said in opening remarks Monday. “Its benefit-risk profile is unfavorable and should be withdrawn from the market.”
The dispute is likely to increase scrutiny of the agency’s so-called accelerated approval program, which allows drugs like Makena to go on the market based on promising early results while additional, usually larger, studies are conducted.
“Makena is being used as an example of the many different criticisms of this program,” said Rachel Sachs, a food and drug law specialist 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 it presents.”
At best, the accelerated approval program is credited with speeding the availability of breakthrough HIV and cancer therapies. But over the past decade, the FDA has been increasingly criticized for failing to fast-track drugs with incomplete or inconclusive supporting data, including a large number of expensive cancer drugs on the market.
In recent years, the FDA’s oncology division has begun pushing 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 that suggested it reduced the rate of preterm birth in women with a history of early birth. Makena consists of a synthetic version of the hormone progesterone, which helps the uterus grow and maintain a pregnancy. Women can start the vaccines 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 resulted in lower rates of birth defects and death among newborns.
But results from an international study of 1,700 women published in 2019 showed that the drug neither reduced premature births — as originally thought — nor led to healthier outcomes for babies, while increasing the risk of blood clots, depression and other side effects in mothers.
In information documents released this month, the FDA said leaving Makena on the market “raises false hopes, the risks associated with the treatment and other burdens” such as excessive medical costs. According to a recent federal report, the US has spent $700 million on Makena since 2018 through various government programs, such as Medicaid and Veterans Affairs.
The FDA’s opinion also applies to several generic versions of the shot.
Drugmaker Covis claims that Makena is effective and that flaws in the 2019 study cloud its benefit. The Luxembourg-based company said black women were at higher risk of preterm birth, but made up only 7% of women in the international study, compared with 59% in the original US study used for approval. He wants time to do another study in higher-risk patients, especially black Americans.
A patient group created with funding from Covis, the Alliance to Prevent Preterm Birth, made similar arguments in letters to the FDA.
“We believe there is no good public health reason to deny” patients and doctors access to Makena, the company said in an emailed statement.