FDA Proposes Makena Be Withdrawn From the Market

Makena received accelerated approval in 2011 to reduce the risk of preterm birth in women with a singleton pregnancy who have a history of singleton spontaneous preterm birth.

The Food and Drug Administration’s (FDA) Center for Drug Evaluation and Research (CDER) has proposed that Makena (hydroxyprogesterone caproate; AMAG), and its generic equivalents, be withdrawn from the market based on a postmarketing study that failed to show clinical benefit. 

Makena received accelerated approval in 2011 to reduce the risk of preterm birth in women with a singleton pregnancy who have a history of singleton spontaneous preterm birth. As part of this approval, the Company was required to conduct a confirmatory trial (PROLONG), which included 1710 patients randomized to receive weekly injections of Makena or placebo.

The trial aimed to determine whether treatment with Makena reduced the rate of preterm birth less than 35 weeks, 0 days of gestation in women with a previous singleton spontaneous preterm delivery, as well as the rate of neonatal mortality and morbidity (measured by a composite index comprised of: neonatal death, grade 3 or 4 intraventricular hemorrhage, respiratory distress syndrome, bronchopulmonary dysplasia, necrotizing enterocolitis, proven sepsis).

Results showed that the trial did not meet the co-primary end points. The incidence of preterm delivery at <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 Company, the difference in results was influenced by the study population, as the first trial included a higher risk population than the PROLONG study. Based on these findings, the FDA’s Bone Reproductive and Urologic Drugs Advisory Committee voted 9 to 7 in favor of pursuing withdrawal of Makena from the market in October 2019.

Commenting on the study findings, Sean Blackwell MD, Chair of the Department of Obstetrics, Gynecology, and Reproductive Sciences at the McGovern Medical School, UTHealth at Houston, said: “The PROLONG trial did not re-affirm efficacy, in my opinion, because it did not include enough women at high enough preterm birth risk. Given the results of the original NICHD trial, removing the ability for physicians and their patients to make a shared decision on the benefits and risks of the only FDA-approved medication to prevent preterm birth is disappointing.”

The CDER has issued a notice of opportunity for a hearing to AMAG Pharmaceuticals, along with the application holders for the approved generics to Makena. The Company will have 15 days to respond to the FDA indicating whether they would like to proceed with a hearing. Makena and its approved generic equivalents will remain on the market until the manufacturers remove the drugs or the FDA Commissioner mandates their removal.

According to the FDA, health care professionals are urged to discuss the benefits, risks and uncertainties of Makena with their patients. The FDA intends to hold a meeting with experts in obstetrics, neonatal care, and clinical trial design to further discuss how to treat preterm birth.

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AMAG is evaluating its full range of potential options and believes the totality of clinical data on Makena supports its continued positive benefit-risk profile, according to a Company statement.

“We disagree with the FDA’s proposal to withdraw Makena without having the opportunity to meet with them to discuss the generation of additional effectiveness data while preserving access for patients to the only FDA approved treatment option for indicated women,” said AMAG CEO Scott Myers. “We are reviewing our options, including the opportunity to request an oral hearing, and will respond to the agency within the allotted time.”

For more information visit fda.gov.


  1. CDER proposes withdrawal of approval for Makena. https://www.fda.gov/drugs/drug-safety-and-availability/cder-proposes-withdrawal-approval-makena. Accessed October 6, 2020. 
  2. AMAG Pharmaceuticals provides update on FDA’s proposal regarding Makena® (hydroxyprogesterone caproate Injection). https://www.amagpharma.com/news/amag-pharmaceuticals-provides-update-on-fdas-proposal-regarding-makena-hydroxyprogesterone-caproate-injection/. Accessed October 6, 2020.