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Only Drug to Prevent Preterm Birth Set to Leave the Market

— Decision follows FDA advisory committee recommendation for withdrawal

by Crystal Phend, Contributing Editor, 鶹ý

MedpageToday
A photo of a Makena injection pen over the FDA logo.

Injectable 17-alpha hydroxyprogesterone caproate (17-OHPC; Makena) for preterm birth will exit the market following an FDA advisory panel's recommendation that the agency withdraw its approval, Covis Pharma .

The controversial drug has been the only medication with an indication to reduce the risk of preterm birth for pregnant women with a history of at least one spontaneous preterm birth.

However, substantial questions about the efficacy of 17-OHPC arose after the PROLONG trial, the confirmatory study FDA mandated as part of its conditional approval, failed to show any benefits.

In PROLONG, the drug didn't reduce births at less than 35 weeks gestation compared with controls (11.0% vs 11.5%; RR 0.95, 95% CI 0.71-1.26), neonatal morbidity index (5.6% vs 5.0%; RR 1.12, 95% CI 0.68-1.61), or any secondary endpoints, such as frequency of fetal/infant death or maternal outcomes.

After that data emerged in October 2019, FDA quickly called a meeting of advisors over what to do next. About a week later, that group voted 9-7 to recommend withdrawing approval. But the drugmaker at the time, AMAG Pharmaceuticals, didn't voluntarily withdraw the drug.

So in October 2022, the FDA held another advisory panel meeting, which again voted for withdrawal of the drug and its generics, this time almost unanimously (14-1).

Even in announcing capitulation, Covis Pharma maintained that "relevant safety and efficacy data continue to support the approval of Makena, at least in a narrower indication."

It explained the delay between the FDA panel vote and the announcement as an issue with FDA: "Shortly after the hearing, Covis outlined a plan for voluntary withdrawal that would have obviated the need for further proceedings. The request included a wind-down period that would allow current patients to complete their 21-week course of treatment and for only remaining inventory to be exhausted. CDER [FDA's Center for Drug Evaluation and Research] was not in agreement with the proposal, and requested that the proceedings continue until concluded with a decision from the FDA Commissioner and Chief Scientist."

Exactly when the withdrawal will happen remains unclear, as Covis Pharma noted that a wind-down period will be needed, which the FDA hasn't signed off on yet.

"Given CDER's acknowledgement at the hearing that Makena does not have significant safety concerns and that an immediate withdrawal would be disruptive to patients in the middle of an indicated course of treatment, the company respectfully requests that once any final order is issued, the effective date be set to allow for a wind-down that would best serve the interests of patients," it said in the announcement. "As the company awaits a final decision by the FDA, Makena remains approved and the product label is unchanged at this time."