[10/5/2020] Today, the U.S. Food and Drug Administration’s Center for Drug Evaluation and Research (CDER) proposed that Makena (hydroxyprogesterone caproate injection) be withdrawn from the market because the required postmarket study failed to verify clinical benefit and we have concluded that the available evidence does not show Makena is effective for its approved use.

Makena received accelerated approval in 2011 to reduce the risk of preterm birth in women who previously had a spontaneous (unexplained) preterm birth, which is delivery of a baby before 37 weeks. As part of this accelerated approval, the company was required to conduct a clinical trial to confirm the drug provided clinical benefit to newborns. A drug that prevents preterm birth is helpful if it ultimately improves the babies’ health. The required confirmatory trial failed to show that Makena is effective for improving the health of babies born to women with a history of unexplained preterm birth. We also determined that the available evidence does not show that Makena reduces the risk of preterm birth. Therefore, CDER has proposed that Makena be withdrawn from the market and has issued a notice of opportunity for a hearing (NOOH) to the application holder of Makena, AMAG Pharmaceuticals. FDA also sent the NOOH to the application holders for the approved generics to Makena for an opportunity to comment.

Makena and its approved generic equivalents will remain on the market until the manufacturers decide to remove the drugs or the FDA Commissioner mandates their removal. If AMAG Pharmaceuticals requests a hearing, the FDA Commissioner will determine whether to hold a public hearing and, following such hearing, decide whether to withdraw approval of Makena and its approved generic equivalents.

In the interim, we recommend that health care professionals discuss Makena’s benefits, risks and uncertainties with their patients to decide whether to use Makena while a final decision is being made about the drug’s marketing status. We intend to hold a meeting with experts in obstetrics, neonatal care, and clinical trial design to discuss how to facilitate development of effective and safe therapies to treat preterm birth.

FDA approved Makena under the accelerated approval pathway because preterm birth can be serious and life-threatening for the baby, and there were no approved treatments for preterm birth. Additionally, a single trial in the original application showed that Makena lowered the rate of preterm birth, a finding that we thought was reasonably likely to predict improvement to the health of the baby. However, after evaluating the results of the required confirmatory trial, it was determined that the available evidence does not show that Makena reduces the risk of preterm birth.

FDA encourages health care professionals and patients to report adverse events with the use of any medication to FDA’s MedWatch Adverse Event Reporting program:

  • Complete and submit the report online; or
  • Download and complete the form, then submit it via fax at 1-800-FDA-0178