EMA Suspends Hydroxyprogesterone Caproate Medicines in Europe

The European Medicines Agency (EMA) announced on May 17, 2024 that its Pharmacovigilance Risk Assessment Committee (PRAC) has recommended the suspension of medicines that contain 17-hydroxyprogesterone caproate (17-OHPC). Drugs that contain 17-OHPC are used to prevent premature birth or loss of pregnancy. Other authorized uses include treatment of gynecological and fertility disorders.

The recommendation comes after a PRAC review that found there is a possible “but unconfirmed” risk of cancer developing in people that were exposed to 17-OHPC in the womb. The review also found that 17-OHPC is not effective in preventing premature birth and may not be effective in other authorized uses.

“In view of the concern raised by the possible risk of cancer in people exposed to 17-OPHC in the womb, together with the data on the effectiveness of 17-OHPC in its authorized uses, the PRAC considered that the benefits of 17-OHPC do not outweigh its risks in any authorized use. The Committee is therefore recommending the suspension of the marketing authorizations for these medicines. Alternative treatment options are available,” EMA stated in a press release (1).

PRAC will develop direct healthcare professional communication (DHPC) for 17-OPHC medicines that recommends use of alternative treatment options. Once approved, the DHPC will be provided to healthcare professionals by the marketing authorization holder.

Results from a large population-based study that looked at the risk of cancer in those exposed to 17-OHPC in the womb was used to make PRAC’s decision. While data suggested there was an increased risk of cancer compared to people not exposed to these medications, the study had limitations, according to PRAC. “The Committee therefore concluded that the risk of cancer in people exposed to 17-OHPC in the womb is possible but cannot be confirmed due to uncertainties” (2). PRAC also considered effectiveness data of other authorized uses of these medicines in a study of more than 1700 pregnant women with a history of preterm delivery. PRAC found 17-OHPC to be no more effective than placebo in preventing recurrent premature birth or medical complications.

In April 2023, FDA withdrew the approval of Makena (hydroxyprogesterone caproate injection) after post-marketing data found that the drug was not effective and there were risks associated with its use. Makena had been originally approved under FDA’s accelerated approval pathway in 2011 (3).

“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 in a press release at the time of the withdrawal (3). “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.”

“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 in the release. “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.”

References

1. EMA. Meeting Highlights from the Pharmacovigilance Risk Assessment Committee (PRAC) 13-16 May 2024. Press Release. May 17, 2024.
2. EMA. Hydroxyprogesterone Caproate-containing Medicinal Products–Referral. ema.europa.eu (accessed May 17, 2024).
3. FDA. FDA Commissioner and Chief Scientist Announce Decision to Withdraw Approval of Makena. Press Release. April 6, 2023.