FDA Yanks Only Preterm Birth Drug, Effective Immediately

— Months after advisors recommended Makena's approval be withdrawn, FDA announces final decision

by Rachael Robertson, Enterprise & Investigative Writer, �鶹��ý April 6, 2023

After a years-long saga, the FDA has of injectable 17-alpha hydroxyprogesterone caproate (17-OHPC; Makena), which was initially approved over a decade ago to reduce the risk of recurrent preterm birth.

"Effective today, Makena and its generics are no longer approved and cannot lawfully be distributed in interstate commerce," the agency said in its announcement on Thursday.

This final decision comes months after the FDA's Obstetrics, Reproductive, and Urologic Drugs Advisory Committee voted 14-1 to revoke approval of the drug and its generics in October 2022.

Last month, Covis Pharma announced that 17-OHPC would leave the market, but had pushed for a wind-down period to allow current patients still receiving treatment to complete their 21-week course of therapy.

Originally approved in 2011 under the accelerated approval pathway, 17-OHPC was indicated to reduce the risk of preterm birth in pregnant women who have a history of spontaneous preterm birth. , Black and Indigenous mothers, as well as mothers younger than 18 and older than 35, are at higher risk for preterm birth.

"Nothing in this opinion today is intended to minimize these concerns -- to the contrary, our hope is that this decision will help galvanize further research," said FDA Chief Scientist Namandjé Bumpus, PhD, in the FDA press release.

In the postmarketing confirmatory trial conducted in 2019, required under the accelerated approval program, results showed that 17-OHPC did not have a statistically significant effect on preterm births before 35 weeks' gestation (relative risk [RR] 0.95, 95% CI 0.71-1.26), neonatal morbidity index (RR 1.12, 95% CI 0.68-1.61), or any secondary endpoints, such as frequency of fetal/infant death or maternal outcomes.

"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 -- particularly in light of the fact that this serious condition has a disparate impact on communities of color, especially Black women," said FDA Commissioner Robert Califf, MD, in a statement. "Fundamentally, however, the touchstone of FDA drug approval is a favorable benefit-risk assessment; without that favorable assessment, the drug should not have the status of being FDA-approved."

Following the failed confirmatory study, the FDA's Center for Drug Evaluation and Research recommended that the drugmaker, AMAG Pharmaceuticals at the time, withdraw the drug from the market, but the company did not follow this guidance, leading to the October 2022 hearing.

With 17-OHPC leaving the market, there are now no FDA-approved drugs for reducing the risk of preterm birth.

Rachael Robertson is a writer on the �鶹��ý enterprise and investigative team, also covering OB/GYN news. Her print, data, and audio stories have appeared in Everyday Health, Gizmodo, the Bronx Times, and multiple podcasts.