AMAG Pharmaceuticals announced the U.S. Food and Drug Administration’s (FDA) Bone, Reproductive and Urologic Drugs Advisory Committee met to better understand and interpret the PROLONG (Progestin’s Role in Optimizing Neonatal Gestation) confirmatory clinical trial for Makena® (hydroxyprogesterone caproate injection), a treatment approved to reduce preterm birth in pregnant women who have had a prior spontaneous preterm birth. While the committee discussed multiple questions, in a mixed vote on the key question, nine advisory committee members voted to recommend that the FDA pursue withdrawal of approval for Makena and seven committee members voted to leave the product on the market under accelerated approval and require a new confirmatory trial. Among the clinicians on the advisory committee, five of the six who practice obstetrics voted to keep Makena on the market and generate more data. AMAG agrees with several committee members who voiced concern that withdrawal of Makena would leave providers with no safe treatment options for pregnant women. The advisory committee's recommendation, while not binding, will be considered by the FDA in making its decision.
“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,” said Julie Krop, M.D., chief medical officer at AMAG. “Preterm birth is an urgent public health crisis and the implications of leaving pregnant women and providers without access to therapy that is manufactured in a safe and regulated way is profoundly troubling. 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.”
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Makena’s active ingredient, 17α hydroxyprogesterone caproate (often referred to as 17P), is the only FDA-approved treatment for pregnant women who have had a prior spontaneous preterm birth (which is a substantial risk factor for recurrent preterm birth). 17P has been recognized as the standard of care and used for more than a decade by healthcare providers to treat patients with a history of spontaneous preterm birth, which represents approximately 130,000 births a year in the United States.
The approval of Makena was based on the landmark Meis trial, conducted by the National Institute of Child Health and Human Development and the Maternal-Fetal Medicine Units Network and published in the New England Journal of Medicine in 2003. The PROLONG trial was later conducted as part of an FDA approval commitment. Comprised of more than 1,700 pregnant women, PROLONG represents the largest trial of any progestogen studied for preterm birth prevention and is also the largest trial of a drug treating an orphan condition. It enrolled more than 75 percent of its patients from outside of the U.S., which was necessary given the routine use of 17P as the standard of care.