FDA Officially Withdraws Approval of Makena After Lengthy Debate

Following an extensive debate, the FDA has officially announced it has withdrawn the approval of Makena (Hydroxyprogesterone caproate, Covis Pharma Group), according to a joint statement issue by the FDA Commissioner and Chief Scientist.¹ Previously, Makena was the only treatment FDA-approved for reducing the risk of preterm birth in women who experienced spontaneous preterm birth in the past.²

"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 M. Califf, MD. "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."

In 2011, Makena received approval under the accelerated approval pathway because of “a determination that the sponsor had demonstrated a drug effect on an intermediate clinical endpoint that was reasonably likely to predict clinical benefit,” according to the FDA.

The approval required the sponsor to conduct a post-marketing study. However, findings from the study did not confirm clinical benefit, ultimately leading the FDA's Center for Drug Evaluation and Research (CDER) to propose withdrawing the approval in 2020. Per the FDA, a hearing was requested by the sponsor and subsequently held in October 2022.

After the hearing, both the FDA Commissioner and Chief Scientist reviewed submissions by CDER and the sponsor (Covis Pharma), public comments to the docket, the meeting transcript, and the Presiding Officer's report, ultimately deciding to withdraw the approval of Makena, as well as its generic versions.

In previous coverage from Contemporary OB/GYN®, Covis announced in March 2023 that it had voluntarily withdrawn Makena from the market.² “We recognize the attention the agency has directed to this issue, particularly given the complexity around withdrawing a drug with mixed efficacy data and a positive safety profile ,and welcome the opportunity to discuss an appropriate wind-down plan for patients,” said Raghav Chari, PhD, chief innovation officer at Covis, in a company press release announcing the voluntary withdrawal.³

"We acknowledge at the outset the serious problems of preterm birth with respect to both maternal and neonatal health and the contribution of institutional forces that have led to health disparities, including preterm birth, among Black women," said FDA Chief Scientist Namandjé Bumpus, PhD "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."

The FDA said it acknowledges that despite this approval withdrawal, some supply of Makena and its generics have already been distributed. The agency recommends patients speak with their health care provider if they have any questions and visit FDA.gov for more information.

This article originally appeared in Contemporary OB/GYN.

References

1. FDA Commissioner and Chief Scientist announce decision to withdraw approval of Makena. FDA. April 6, 2023. Accessed, April 6, 2023. https://www.fda.gov/news-events/press-announcements/fda-commissioner-and-chief-scientist-announce-decision-withdraw-approval-makena

2. Krewson C. Covis withdraws Makena from the market. Contemporary OB/GYN. March 9, 2023. Accessed April 6, 2023. https://www.contemporaryobgyn.net/view/covis-withdraws-makena-from-the-market

3. Covis Pharma responds to presiding officer’s report summarizing FDA advisory committee hearing. Covis Pharma. March 7, 2023. Accessed March 9, 2023. https://covispharma.com/index.php/covis-pharma-responds-to-presiding-officers-report-summarizing-fda-advisory-committee-hearing/