日前，美国食品药品管理局（FDA）批准了首个旨在预防孕妇流产或早产、商品名为Makena 和化学名为hydroxyprogesterone caproate的注射制剂。

据报道，该药可用于预防孕妇于妊娠37周前流产或早产。需要指出的是：1）若要达到预防流产或早产的目的，必须于妊娠16周时（最晚不得迟于21周）开始每周注射给药1次；2）本品仅适用于单胎妊娠的女性，特别是既往至少有一次自然流产或早产病史，而不宜用于双胎或多胎妊娠者。

本品在研发的过程中，科研人员将463个年龄在16～43岁之间、且已怀孕和既往有自然流产或早产史的女性随机分为两组进行了观察，结果显示接受Makena治疗的孕妇于妊娠37周前分娩者仅占37%，未接受本品治疗组于妊娠37周前分娩者则高达55%。该结果提示本品在预防流产或早产等方面的确安全有效。

FDA approves drug to reduce risk of preterm birth in at-risk pregnant women

The U.S. Food and Drug Administration today approved Makena (hydroxyprogesterone caproate) injection to reduce the risk of preterm delivery before 37 weeks of pregnancy, in pregnant women with a history of at least one spontaneous preterm birth. 

The drug is not intended for use in women with a multiple pregnancy, such as a twin pregnancy, or other risk factors for preterm birth. 

　　The FDA approved Makena under the agency accelerated approval regulations that allow promising drugs to be approved based on a surrogate endpoint benefit (here, reducing the risk of delivery before 37 weeks of pregnancy) that is reasonably likely to predict a clinical benefit.

Under these regulations, the manufacturer must conduct additional studies after the product is approved to demonstrate that the drug does, in fact, have a clinical benefit.  An international trial is ongoing to learn if there is also improvement in the outcome of babies born to women given Makena. Such outcomes include reducing the number of babies who do not survive or who suffer serious health problems shortly after birth. 

　　“Preterm birth is a significant public health issue in the United States,” said Sandra Kweder, M.D., deputy director of the Office of New Drugs in the FDA’s Center for Drug Evaluation and Research. “This is the first drug approved by the FDA that is indicated to specifically reduce this risk.”

A health care provider would give Makena once a week by injection into the hip. Treatment should begin at 16 weeks and no later than 21 weeks of pregnancy.

The FDA reviewed data on the safety and effectiveness of Makena in a multicenter randomized double-blind clinical trial. The study included 463 women 16 to 43 years of age who were pregnant with a single fetus and had a history of a prior spontaneous preterm birth. Among women treated with Makena, 37 percent delivered early (before 37 weeks) as compared with 55 percent of women in the control group. 

A separate study evaluated the development of children born to mothers enrolled in the controlled trial. In this study, children ages 2.5 years to 5 years reached similar developmental targets, regardless of the mother treatment.  The confirmatory study that is ongoing will be followed by a similar infant follow-up study, to be completed about 2018.  That study is expected to include 580-750 infants, depending on the number of study sites and mothers willing to participate. 

The most common side effects reported with Makena included pain, swelling, or itching at the injection site; hives, nausea and diarrhea. Serious adverse reactions were rare; there was a single report each of blood clot in the lungs (pulmonary embolism) and an infection at the injection site.

The FDA originally approved hydroxyprogesterone caproate under the trade name Delalutin in 1956 for use in pregnant women. The approved indications include threatened miscarriage. The original manufacturer requested the withdrawal of Delalutin from the market in 2000 for reasons unrelated to safety.

Consumers and health care professionals are encouraged to report adverse events from medications to the FDA MedWatch program at 800-FDA-1088 or online at www.fda.gov/medwatch/how.htm¹.

　　Makena is sponsored by Hologic, Inc., based in Sunnyvale, California.