AMAG Pharmaceuticals said Friday that a confirmatory study of Makena (hydroxyprogesterone caproate) in patients with a history of a prior spontaneous singleton preterm delivery failed to meet its co-primary endpoints. Shares in the company, which gained approval of Makena in this indication in 2011, fell up to nearly 21 percent on the news.
The PROLONG trial, which was conducted as part of an accelerated approval commitment with the FDA, randomised around 1700 pregnant women to treatment with Makena or placebo. The co-primary endpoints of the study were the incidence of preterm delivery at less than 35 weeks and the percentage of patients who met the criteria for the pre-specified neonatal morbidity and mortality composite index.
According to AMAG, top-line results showed that the incidence of preterm delivery at less than 35 weeks was 11 percent in the Makena group versus 11.5 percent for placebo, while the percentage of patients who met criteria for the pre-specified neonatal morbidity and mortality composite index was 5.4 percent and 5.2 percent, respectively, in the two groups.
Chief medical officer Julie Krop said that following approval, Makena "became the standard of care for pregnant women who have had a prior spontaneous preterm birth," noting that "this led to a reluctance by US physicians to enrol their patients in a placebo-controlled clinical trial." Krop explained that as such, "the majority of patients in the PROLONG trial were enrolled…predominantly from Eastern European countries, with very different demographics" compared to the study, dubbed Meis, that supported approval of Makena.
"In light of these recent findings and the inconsistencies with prior clinical evidence, we plan to conduct additional sub-group analyses of the PROLONG data, particularly focusing on patients at the highest risk of preterm delivery and the subset of patients enrolled in the US," Krop added.
AMAG gained rights to Makena via its purchase of Lumara Health's maternal health business in a deal potentially worth more than $1 billion, which was completed in 2014. A subcutaneous formulation of the therapy was authorised by the FDA last year for use in women pregnant with one child who spontaneously delivered a preterm baby previously.
Sales of Makena and its authorised generic totalled $322.3 million last year, down from $387.2 million in 2017, with the decline due to decreased revenue from the intramuscular version of the product. Meanwhile, Slayback Pharma received FDA clearance of the first generic version of the injectable formulation of Makena in January.
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