FDA Advisers Recommend Pulling Drug to Prevent Preterm Births From Market

The FDA doesn’t have to follow the recommendations of its advisers, but often does. The agency, which has been trying for years to get Makena withdrawn, is expected to order its removal within months.

“It seems clear to me that efficacy was not demonstrated,” said advisory panel member Susan Ellenberg, a professor emerita of biostatistics, medical ethics and health policy at the University of Pennsylvania who voted for withdrawal. “I think we’re basically back to square zero.”

The company, however, believes in the data behind the drug, according to Francesco Tallarico, general counsel and head of government affairs for Covis. Still, he said that he couldn’t promise the company would pay for another study to prove the treatment’s effectiveness. “At this time I can’t rule anything out, and we’re going to have to explore all of our options available to us.”

The agency approved Makena in 2011 to treat women at risk of giving birth early because they had done so previously. Makena is a weekly injection of a synthetic version of the hormone progesterone. Premature births can mean severe health problems for newborns.

The FDA greenlighted the drug using an accelerated process that required its manufacturer to confirm the drug’s benefit with further study. In 2019, however, Makena failed to work in the follow-up trial, kicking off the FDA’s efforts to pull the drug from the market.

The agency usually relies on companies to pull their accelerated-approval drugs voluntarily if follow-up studies show they don’t work. Only rarely has the FDA itself removed a drug.

How the agency proceeds with Makena could suggest its power and willingness to pull drugs that got accelerated approval.

Obstetricians and other reproductive-health experts serving on the FDA’s Obstetrics, Reproductive and Urologic Advisory Committee first voted against the drug in 2019. Covis appealed the decision based on new analyses of its data, and the FDA granted the company another hearing.

At the latest panel meeting, Covis argued that its drug might be most helpful to Black women, who are at higher risk for preterm birth. Those women weren’t well-represented in the follow-up study that the drug failed, the company said.

Medicaid spent nearly $700 million on Makena between 2018 and 2021, the Department of Health and Human Services’ inspector general said last month. Covis said a Makena injection costs $300 on average for commercial and government payers.

Covis, which is owned by private-equity firm

Apollo Global Management Inc.,

asked that Makena be allowed to remain approved for high-risk patients while it conducts another randomized, controlled study, which it estimated would take four to six years.

The FDA said that dozens of Makena studies found the drug didn’t reduce preterm births, and that the one study that indicated a potential benefit, on which the drug’s approval was based, was an outlier.

The drug also comes with potential side effects, including blood clots, allergic reactions and depression. “This has to be a concern, especially when benefit has not been established,” said Peter Stein, director of the FDA’s office of new drugs.

Covis said a decade’s worth of use showed that the safety risks with Makena were insignificant.

The agency said the injection showed no benefits for any specific groups of people in any studies and that if the drug remained on the market, a new trial would struggle to find volunteers, since patients who wanted the drug would be unlikely to risk taking a placebo with prescriptions available.

Write to Liz Essley Whyte at [email protected]

The FDA doesn’t have to follow the recommendations of its advisers, but often does. The agency, which has been trying for years to get Makena withdrawn, is expected to order its removal within months.

“It seems clear to me that efficacy was not demonstrated,” said advisory panel member Susan Ellenberg, a professor emerita of biostatistics, medical ethics and health policy at the University of Pennsylvania who voted for withdrawal. “I think we’re basically back to square zero.”

The company, however, believes in the data behind the drug, according to Francesco Tallarico, general counsel and head of government affairs for Covis. Still, he said that he couldn’t promise the company would pay for another study to prove the treatment’s effectiveness. “At this time I can’t rule anything out, and we’re going to have to explore all of our options available to us.”

The agency approved Makena in 2011 to treat women at risk of giving birth early because they had done so previously. Makena is a weekly injection of a synthetic version of the hormone progesterone. Premature births can mean severe health problems for newborns.

The FDA greenlighted the drug using an accelerated process that required its manufacturer to confirm the drug’s benefit with further study. In 2019, however, Makena failed to work in the follow-up trial, kicking off the FDA’s efforts to pull the drug from the market.

The agency usually relies on companies to pull their accelerated-approval drugs voluntarily if follow-up studies show they don’t work. Only rarely has the FDA itself removed a drug.

How the agency proceeds with Makena could suggest its power and willingness to pull drugs that got accelerated approval.

Obstetricians and other reproductive-health experts serving on the FDA’s Obstetrics, Reproductive and Urologic Advisory Committee first voted against the drug in 2019. Covis appealed the decision based on new analyses of its data, and the FDA granted the company another hearing.

At the latest panel meeting, Covis argued that its drug might be most helpful to Black women, who are at higher risk for preterm birth. Those women weren’t well-represented in the follow-up study that the drug failed, the company said.

Medicaid spent nearly $700 million on Makena between 2018 and 2021, the Department of Health and Human Services’ inspector general said last month. Covis said a Makena injection costs $300 on average for commercial and government payers.

Covis, which is owned by private-equity firm

Apollo Global Management Inc.,

asked that Makena be allowed to remain approved for high-risk patients while it conducts another randomized, controlled study, which it estimated would take four to six years.

The FDA said that dozens of Makena studies found the drug didn’t reduce preterm births, and that the one study that indicated a potential benefit, on which the drug’s approval was based, was an outlier.

The drug also comes with potential side effects, including blood clots, allergic reactions and depression. “This has to be a concern, especially when benefit has not been established,” said Peter Stein, director of the FDA’s office of new drugs.

Covis said a decade’s worth of use showed that the safety risks with Makena were insignificant.

The agency said the injection showed no benefits for any specific groups of people in any studies and that if the drug remained on the market, a new trial would struggle to find volunteers, since patients who wanted the drug would be unlikely to risk taking a placebo with prescriptions available.

Write to Liz Essley Whyte at [email protected]