AMAG Pharmaceuticals has reported that the PROLONG trial conducted to assess the use of Makena (hydroxyprogesterone caproate injection) in reducing the risk of preterm birth has failed to achieve primary objectives.
Top-line results showed that a statistically significant difference was not observed between the treatment and placebo arms for the co-primary endpoints.
The trial’s co-primary endpoints were incidence of preterm delivery at less than 35 weeks and the proportion of patients meeting criteria for the pre-specified neonatal morbidity and mortality composite index.
Makena is a progestin intended to mitigate the risk of preterm birth in women with a history of singleton spontaneous preterm birth. It is indicated for those who are pregnant with a single baby.
The US Food and Drug Administration (FDA) approved the drug in February 2011 and granted orphan drug exclusivity until 3 February 2018.
PROLONG is a randomised, double-blinded, placebo-controlled trial that was performed in around 1,700 pregnant women as part of a commitment under the FDA’s ‘Subpart H’ accelerated approval process.
In addition to the co-primary endpoints, the trial data showed comparable adverse event profile between the treatment and placebo group.
Adverse events of special interest, including miscarriage and stillbirth, were observed to be infrequent and similar between the arms.
The FDA’s approval was based on results from the multi-centre, randomised, double-blind, placebo-controlled Meis trial.
Findings from this trial showed a statistically significant and clinically relevant decrease in the rate of preterm birth at 37 weeks in the Makena arm, compared to placebo.
To address inconsistencies in the clinical evidence for Makena, the company plans to carry out additional sub-group analyses of the PROLONG results.
AMAG Pharmaceuticals chief medical officer Julie Krop said: “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.
“We will work closely with our publications committee to further assess the data, submit the findings to the FDA, and prepare the data for peer-reviewed publication.”
Makena’s direct clinical benefit, such as improvement in neonatal mortality and morbidity, has not been demonstrated in any controlled trials.