The FDA 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’s 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’s
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.