Following a meeting to discuss the findings from a post-approval confirmatory trial for Makena (hydroxyprogesterone caproate; AMAG), the Food and Drug Administration (FDA)’s Bone, Reproductive and Urologic Drugs Advisory Committee voted 9 to 7 in favor of pursuing withdrawal of the product from the market.
Makena is currently indicated to reduce the risk of preterm birth in women with a singleton pregnancy who have a history of singleton spontaneous preterm birth. The product was granted conditional approval in 2011 based on data from a placebo-controlled trial which showed that weekly injections of Makena reduced the rate of recurrent preterm delivery in high-risk women. However, as part of this conditional approval, the Company was required to conduct a confirmatory study (PROLONG) of Makena.
The PROLONG trial included 1710 patients who were randomized to receive weekly injections of Makena or vehicle to determine if treatment with Makena reduced the rate of preterm birth <35 weeks, 0 days 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 its 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.
Commenting on the vote, Julie Krop, MD, chief medical officer at AMAG said, “We are disappointed with the nearly split vote on this key question and we are committed to working with the FDA to identify feasible ways to generate additional efficacy data on Makena while retaining current access to the therapy for at-risk pregnant women. For more than a decade, healthcare providers have relied on hydroxyprogesterone caproate to reduce preterm delivery in high-risk patients, which aligns with recently updated treatment recommendations of the American College of Obstetricians and Gynecologists, as well as the Society for Maternal-Fetal Medicine.”
Although not bound by the committees’ recommendations, the FDA does take them into consideration when making decisions on approval.
For more information visit fda.gov.