FDA Withdraws Approval of Makena for Preventing Preterm Birth

The Food and Drug Administration has made a final decision to withdraw the approval of Makena (hydroxyprogesterone caproate) and its generic equivalents, based on a postmarketing study that failed to show clinical benefit.

In 2011, the FDA granted accelerated approval to Makena to reduce the risk of preterm birth in women with a singleton pregnancy who have a history of singleton spontaneous preterm birth. The approval was based on data from a placebo-controlled trial that showed weekly injections of Makena reduced the rate of recurrent preterm delivery in high-risk women. The proportion of patients who delivered preterm at less than 37 weeks was 37.1% for the Makena arm and 54.9% for the control arm (treatment difference, -17.8% [95% CI, -28.0, -7.4]). No overall survival difference was observed in this trial due to the higher rate of miscarriages and stillbirths in the Makena arm.

As part of this approval, the Company was required to conduct a confirmatory trial (PROLONG; ClinicalTrials.gov Identifier: NCT01004029), which included 1710 patients randomly assigned to receive weekly injections of Makena or placebo. Results showed that the trial did not meet the coprimary endpoints. The incidence of preterm delivery at less than 35 weeks was 11.0% for the Makena-treated group and 11.5% for placebo (P =.72). In addition, no statistical differences in the rates of neonatal mortality and morbidity were observed between the groups (5.4% for Makena vs 5.2% for placebo; P =.84). According to the manufacturer, the difference in results was influenced by the study population, as the first trial included a higher risk population than the PROLONG study. 

A review of these findings by the FDA’s Obstetrics, Reproductive, and Urologic Drugs Advisory Committee resulted in the panel voting in favor of the Agency pursuing the withdrawal of Makena from the US market.

Today’s announcement by the FDA’s Commissioner Robert M. Califf, MD and the FDA’s Chief Scientist Namandjé Bumpus, PhD effectively ends the lawful distribution of Makena in the US.

“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 Califf. “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.”