FDA Indicates Pregnancy Drug Makena Does Not Work and Should Be Removed From Market

The controversial drug Makena has been on the market since 2011, for prevention of preterm birth among certain women. However, federal regulators now indicate that it is ineffective and may need to be withdrawn.

The FDA’s Center for Drug Evaluation and Research (CDER) sent a Notice of Opportunity for Hearing (PDF) to the manufacturers of Makena and its generic equivalents on October 5, proposing to withdraw approval of the drug after postmarketing studies have failed to show a clinical benefit.

“First, the required postmarketing clinical trial, Trial 003, failed to verify clinical benefit — Makena showed no improvement in the neonatal composite index versus placebo,” the letter states. “Second, Makena has not been shown to be effective at reducing the risk of recurrent preterm birth or improving neonatal outcomes. Trial 003 not only failed to demonstrate Makena’s benefit to the neonate, but also failed to substantiate any effect of Makena on the surrogate endpoint of gestational age at delivery that was the basis of the initial approval.”

The FDA noted that, in addition to lacking any tangible benefit, Makena side effects may increase the risk of pulmonary embolism, blood clots, allergic reactions, decreased glucose intolerance, fluid retention, and could worsen some conditions commonly experienced by pregnant women, including preeclampsia and depression.

Makena (hydroxyprogesterone) was introduced in 2011, and is the only medication approved for prevention of preterm birth in women who had a prior spontaneous preterm birth. However, it now appears the drug does not actually help achieve its stated purpose.

According to an FDA press release announcing the proposed Makena withdrawal, the agency will give AMAG an opportunity to request a hearing before deciding whether to pull approval and remove Makena from the market, as well as its approved generic equivalents.

The drug and its original manufacturer, KV Pharmaceuticals, gained national notoriety in 2011, after obtaining exclusive rights to sell the medication and charging $1,500 per injection, when compound pharmacies previously sold the product for about $20. Following public outrage, the FDA eventually allowed compounding pharmacies to keep selling the drug, to help get the prices lower. AMAG Pharmaceuticals acquired the rights to the drug in 2014.

Concerns about Makena problems rose following the results of a clinical trial, Progestin’s Role in Optimizing Neonatal Gestation (PROLONG), which found that the drug simply does not work; failing to show any clinical benefits.

In early October 2019, the consumer watchdog group Public Citizen called for a Makena recall in a petition to the agency, saying it did not make sense for the synthetic hormone to remain on the market to be injected into pregnant women, who would then face the risk of side effects without any apparent benefits.

Later that same month, the FDA convened an advisory committee meeting, which voted unanimously that Makena appeared ineffective, and nine of its 16 members voted for the drug to be pulled from the market.

AMAG has 15 days from receipt of the notice to request a hearing. If it does so, the company then has 30 days from the date of the letter to submit data demonstrating there is a “genuine and substantial issue” beyond mere allegations or denials, showing the need for such a hearing.