AMAG’s PROLONG Trial Fails to Hit Endpoints in Preventing Preterm Births

Shares of AMAG Pharmaceuticals plunged more than 17 percent Friday after the company said its Phase III PROLONG trial of Makena failed to demonstrate a statistically significant difference from placebo in preventing preterm births.

The trial examined if Makena, a progestin first approved in 2011, could benefit patients who have shown prior spontaneous singleton preterm delivery. Trial data from PROLONG (Progestin’s Role in Optimizing Neonatal Gestation) showed that Makena benefited 11 percent of patients and placebo 11.5 percent of patients in the incidence of preterm delivery at less than 35 weeks. The PROLONG trial was conducted as part of an approval commitment under the Food & Drug Administration’s “Subpart H” accelerated approval process.

The PROLONG trial enrolled approximately 1,700 pregnant women, over 75 percent of which were enrolled outside the U.S. And the fact that the majority of women who participated in the trial came from outside the United States could have skewed the results, the Waltham, Mass.-based company said.

Makena has been approved by the U.S. Food and Drug Administration in February as a treatment to reduce the risk of preterm birth in women pregnant with one baby and who spontaneously delivered one preterm baby in the past. With that approval, Julie Krop, AMAG’s chief medical officer, said Makena has become a standard of care for pregnant women who have had a prior spontaneous preterm birth. With Makena being considered a standard of care, Krop said there was a reluctance by U.S. physicians to enroll patients in the placebo-controlled PROLONG trial. The majority of patients in the PROLONG trial were from eastern European countries, Krop said, which provided different demographics to the study.

“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 U.S. 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,” Krop said in a statement.

Sean Blackwell, head of the Department of Obstetrics, Gynecology, and Reproductive Sciences at the McGovern Medical School – UTHealth at Houston and chairman of the PROLONG publications committee, said he looks forward to conducting additional analyses of the data. He said the committee will review the data in detail. He said the overall study population of PROLONG is significantly different than those who participated in a previous trial with respect to race, socioeconomic status, and severity of disease. Because of that, Blackwell said the committee will need “sufficient time to thoughtfully interpret these findings in the context of the prior clinical trials.”

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.