PROLONG trial evaluating Makena did not meet endpoint in preterm delivery

AMAG Pharmaceuticals announced topline results from PROLONG, a randomized, double-blinded, placebo-controlled clinical trial evaluating Makena (progestin) in patients with a history of a prior spontaneous singleton preterm delivery. The PROLONG trial was conducted as part of an approval commitment under the Food & Drug Administration’s (FDA) “Subpart H” accelerated approval process. The PROLONG trial did not demonstrate a statistically significant difference between the treatment and placebo arms for the co-primary endpoints: the incidence of preterm delivery at less than 35 weeks (Makena treated group 11.0% vs. placebo 11.5%, p=.72) and the percentage of patients who met criteria for the pre-specified neonatal morbidity and mortality composite index (Makena treated group 5.4% vs 5.2%, p=.84). The adverse event profile between the two arms was comparable. Adverse events of special interest, including miscarriage and stillbirth, were infrequent and similar between the treatment and placebo groups. The PROLONG trial enrolled approximately 1,700 pregnant women, over 75 percent of which were enrolled outside the U.S.

Comment: Makena is a progestin indicated to reduce the risk of preterm birth in women pregnant with a single baby who have a history of singleton spontaneous preterm birth. Makena was approved by the FDA in February 2011 and was granted orphan drug exclusivity through February 3, 2018. In February of 2018, AMAG introduced the prefilled Makena auto-injector containing a short, thin, non-visible needle for subcutaneous use, offering patients and providers a new administration option. A multicenter, randomized, double-blind, vehicle (placebo)-controlled clinical trial (the Meis trial), which served as the basis for the FDA’s approval of Makena, demonstrated a statistically significant and clinically relevant reduction in the rate of preterm birth at 37 weeks in the Makena arm (36.3%) compared to the placebo arm (54.9 %). There are no controlled trials demonstrating a direct clinical benefit, such as improvement in neonatal mortality and morbidity.