FDA Orders Immediate Withdrawal of Unproven Premature Birth Drug Makena

The Food and Drug Administration on Thursday ordered the immediate market withdrawal of a drug intended to prevent premature births, which has remained available for years despite data showing it doesn’t help pregnant women.

The decision follows repeated efforts by Swiss drugmaker Covis Pharma to keep Makena on the U.S. market while it conducted additional studies. The medication was the only drug approved in the U.S. to help reduce the risk of early births in women with a history of preterm deliveries.

In recent months, Covis finally bowed to FDA pressure, proposing a “winding down” period of several months so that women taking the drug could complete their treatment. The FDA rejected that and said Thursday that the action against Makena and several generic versions should take effect immediately.

“Makena and its generics are no longer approved and cannot lawfully be distributed in interstate commerce,” the agency said in a statement.

The injectable drug is a synthetic version of the hormone progesterone, which helps the uterus sustain pregnancy. It can cause side effects, including blood clots, depression and allergic reactions. Given those risks, FDA staffers previously concluded there was no upside to keeping the drug available, given its lack of confirmed benefit.

The final decision by FDA Commissioner Robert Califf and the agency’s chief scientist marks the first time the agency formally forced the removal of a drug that it initially approved based on promising early data. In all prior cases, drugmakers voluntarily pulled medications after the FDA made clear it intended to order removal.

The FDA expedited Makena’s approval in 2011 based on a small study suggesting it reduced rates of premature birth in women who had previously had trouble bringing a pregnancy to term. But results from a 1,700-participant study completed in late 2018 showed the drug neither reduced premature births — as originally thought — nor resulted in healthier outcomes for babies.

The FDA has been working to get the drug off the market since then, though Covis repeatedly appealed for more time to conduct further research.

In October, the company failed to convince a panel of outside FDA advisers that the drug should stay on the market for women who face higher risks of early deliveries, including Black women.

About 10% of U.S. births come too early — before 37 weeks, raising the risk of serious health problems and even death in infants.

“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,” Califf said in a statement Thursday. Women who have a current prescription for the drug should direct any questions to their doctor, the agency said.

The FDA has faced pressure to crack down on unproven drugs cleared under its accelerated approval program, which since the early 1990s has allowed dozens of drugs to launch based on early results.

The flipside of the program means removing drugs if their initial promise isn’t confirmed by later studies. Researchers and government watchdogs have chronicled problems with FDA’s oversight, including delays in quickly removing drugs with failed or missing confirmatory studies. In the last two years the FDA has stepped up efforts to remove unproven approvals, mainly from cancer therapies.

​The Food and Drug Administration on Thursday ordered the immediate market withdrawal of a drug intended to prevent premature births, which has remained available for years despite data showing it doesn’t help pregnant women.

The decision follows repeated efforts by Swiss drugmaker Covis Pharma to keep Makena on the U.S. market while it conducted additional studies. The medication was the only drug approved in the U.S. to help reduce the risk of early births in women with a history of preterm deliveries.

In recent months, Covis finally bowed to FDA pressure, proposing a “winding down” period of several months so that women taking the drug could complete their treatment. The FDA rejected that and said Thursday that the action against Makena and several generic versions should take effect immediately.

“Makena and its generics are no longer approved and cannot lawfully be distributed in interstate commerce,” the agency said in a statement.

The injectable drug is a synthetic version of the hormone progesterone, which helps the uterus sustain pregnancy. It can cause side effects, including blood clots, depression and allergic reactions. Given those risks, FDA staffers previously concluded there was no upside to keeping the drug available, given its lack of confirmed benefit.

The final decision by FDA Commissioner Robert Califf and the agency’s chief scientist marks the first time the agency formally forced the removal of a drug that it initially approved based on promising early data. In all prior cases, drugmakers voluntarily pulled medications after the FDA made clear it intended to order removal.

The FDA expedited Makena’s approval in 2011 based on a small study suggesting it reduced rates of premature birth in women who had previously had trouble bringing a pregnancy to term. But results from a 1,700-participant study completed in late 2018 showed the drug neither reduced premature births — as originally thought — nor resulted in healthier outcomes for babies.

The FDA has been working to get the drug off the market since then, though Covis repeatedly appealed for more time to conduct further research.

In October, the company failed to convince a panel of outside FDA advisers that the drug should stay on the market for women who face higher risks of early deliveries, including Black women.

About 10% of U.S. births come too early — before 37 weeks, raising the risk of serious health problems and even death in infants.

“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,” Califf said in a statement Thursday. Women who have a current prescription for the drug should direct any questions to their doctor, the agency said.

The FDA has faced pressure to crack down on unproven drugs cleared under its accelerated approval program, which since the early 1990s has allowed dozens of drugs to launch based on early results.

The flipside of the program means removing drugs if their initial promise isn’t confirmed by later studies. Researchers and government watchdogs have chronicled problems with FDA’s oversight, including delays in quickly removing drugs with failed or missing confirmatory studies. In the last two years the FDA has stepped up efforts to remove unproven approvals, mainly from cancer therapies.