AMAG Pharmaceuticals announces topline results from the PROLONG trial evaluating Makena (hydroxyprogesterone caproate injection)

WALTHAM, MA, USA I March 8, 2019 I AMAG Pharmaceuticals, Inc. (NASDAQ:AMAG) announced today topline results from PROLONG (Progestin’s Role in Optimizing Neonatal Gestation), a randomized, double-blinded, placebo-controlled clinical trial evaluating Makena® 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.

“After the initiation of the PROLONG trial and the approval of Makena in the U.S., Makena became the standard of care for pregnant women who have had a prior spontaneous preterm birth. This led to a reluctance by U.S. physicians to enroll their patients in a placebo-controlled clinical trial and therefore, the majority of patients in the PROLONG trial were enrolled outside of the U.S., predominantly from Eastern European countries, with very different demographics compared to the Meis trial[1],” said Julie Krop, M.D., AMAG’s Chief Medical Officer. “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.”

“As Chair of the PROLONG Publications Committee, I look forward to working closely with the clinical team to conduct additional analyses and ensure these data are properly examined through the scientific peer-review process,” said Sean Blackwell, M.D., Chair of the Department of Obstetrics, Gynecology, and Reproductive Sciences at the McGovern Medical School – UTHealth at Houston and Immediate Past President of the Society for Maternal-Fetal Medicine (SMFM). “Our committee will be reviewing the trial data in detail and we will be actively involved in the analysis and interpretation of the findings. It is clear that the overall study population of PROLONG is significantly different than those who participated in the NICHD MFMU[2] trial with respect to race, socioeconomic status, and severity of disease. Thus, we need sufficient time to thoughtfully interpret these findings in the context of the prior clinical trials.” 

About Makena® (hydroxyprogesterone caproate injection)

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.

Makena has certain limitations of use. While there are many risk factors for preterm birth, safety and efficacy of Makena has been demonstrated only in women with a prior spontaneous singleton preterm birth. It is not intended for use in women with multiple gestations or other risk factors for preterm birth.

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.

Makena should not be used in women with any of the following conditions: blood clots or other blood clotting problems, breast cancer or other hormone-sensitive cancers, or history of these conditions; unusual vaginal bleeding not related to the current pregnancy, yellowing of the skin due to liver problems during pregnancy, liver problems, including liver tumors, or uncontrolled high blood pressure. Before patients receive Makena, they should tell their healthcare provider if they have an allergy to hydroxyprogesterone caproate, castor oil, or any of the other ingredients in Makena; diabetes or prediabetes, epilepsy, migraine headaches, asthma, heart problems, kidney problems, depression, or high blood pressure.

In one clinical study, certain complications or events associated with pregnancy occurred more often in women who received Makena. These included miscarriage (pregnancy loss before 20 weeks of pregnancy), stillbirth (fetal death occurring during or after the 20th week of pregnancy), hospital admission for preterm labor, preeclampsia (high blood pressure and too much protein in the urine), gestational hypertension (high blood pressure caused by pregnancy), gestational diabetes, and oligohydramnios (low amniotic fluid levels). Makena may cause serious side effects including blood clots, allergic reactions, depression, and yellowing of the skin and the whites of the eyes. The most common side effect reported with the Makena auto-injector use (and higher than with the Makena intramuscular injection) was injection site pain.

AMAG developed the Makena auto-injector with its device partner Antares Pharma, Inc., which holds issued patents on the auto-injector device and drug-device combination, the last of which expires in 2034. AMAG also holds a U.S. patent directed to subcutaneous administration and dosing of the Makena auto-injector product, which expires in 2036.

For additional product information, including full prescribing information, please visit www.makena.com.

About AMAG

AMAG is a pharmaceutical company focused on bringing innovative products to patients with unmet medical needs. The company does this by leveraging its development and commercial expertise to invest in and grow its pharmaceutical products across a range of therapeutic areas, including women’s health. For additional company information, please visit www.amagpharma.com.

SOURCE: AMAG Pharmaceuticals

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