Health Experts Question Why Makena is Still on the Market Despite FDA Advisors Recommendation to Recall Pregnancy Drug

Although an U.S. Food and Drug Administration (FDA) advisory committee voted several months ago to recommend the pregnancy drug Makena be recalled, due to a lack of clinical benefits and a notoriously high price, health experts are raising concerns that the agency has not taken any action to remove Makena from the market.

Makena (hydroxyprogesterone) was first introduced in 2011, and is the only medication approved for prevention of preterm birth among women who had a prior spontaneous preterm birth. However, critics have been calling for a Makena recall after data suggested that the drug simply does not work, with some clinical trial data even suggesting that Makena could worsen conditions commonly experienced by pregnant women, including preeclampsia and depression.

In October 2022, the Obstetrics, Reproductive and Urologic Drugs Advisory Committee held a three-day hearing to discuss the efficacy of Makena, and voted 14 to 1 to recommend the FDA remove Makena from the market, and voted unanimously (15 to 0) to recognize that the postmarketing Makena trials did not show any benefit to babies.

Two recent editorials published by health experts express alarm about the lack of action taken by the FDA to force a Makena recall, as the pregnancy drug remains on the market in the U.S.

One of the editorials was published in the Journal of the American Medical Association (JAMA) and the other was published by MedPage Today, pointing to problems with the FDA’s accelerated approval process, which can leave ineffective and potentially dangerous drugs on the market once drug manufacturers have established a customer base.

The decision to approve Makena has been widely criticized since the drug was fast tracked through the FDA’s accelerated approval process, based on positive findings from a placebo-controlled trial with only 463 participants.

While the advisory committee’s recommendations are not binding on the FDA, they typically have a significant influence on the agency’s final ruling. Given that this is the second ruling in favor of removing Makena from the market after additional time was allowed for postmarketing clinical data to be collected, a Makena recall was expected to be forthcoming by the FDA.

However, months later, and years after the first time FDA advisors recommended a Makena recall in 2019, Makena is still on the market.

Accelerated Approval Program May Be Preventing Makena Recall

In the JAMA editorial, Harvard Law School researchers blame Makena’s continued presence on the market on problems with the accelerated approval, which is slow to withdraw drugs after they fail confirmatory trials, with drug manufacturers often pointing to the fact that there are patients who have come to rely on the drugs, which may have no substitutes.

In addition, the manufacturer of Makena, Covis Pharma, has vowed to fight any Makena recall attempt.

“Attempts to withdraw a drug like Makena also put the FDA in a difficult position. Despite poor confirmatory trial results, the agency may face pressure from those who have used or want to use the drug,” the JAMA editorial notes. “The FDA may also worry that physicians or patients may dodge the withdrawal by obtaining the drug from other sources, for example, through off-label use (if the drug is otherwise available) or through a compounding pharmacy.”

The editorial notes that keeping Makena on the market this long, despite evidence that it does not work, has cost the U.S. Centers for Medicare and Medicaid Services (CMS) more than $700 million between 2018 and 2021, noting that, for this price, CMS got a drug that did not actually help pregnant women, and increases the risk of cancer, including pediatric brain cancer, in their offspring.

MedPage Today’s editorial points out that Covis Pharma has claimed Makena has benefits for underserved black mothers. However, critics note the clinical trials that led to the drug’s approval had very few black women in it, with 88% of clinical trial subjects being European women.

The editorial notes that when Covis bought Makena, it raised the price from $15 to more than $15,000, which MedPage points out doesn’t seem to suggest Covis is interested in helping an underserved, minority population. The current price for Makena is still about $10,000 per year.

The JAMA editorial proposed a simple solution: make the accelerated approval require a stronger efficacy signal before approval is granted.

Congress is currently considering legislation in the U.S. House of Representatives, the Accelerated Approval Integrity Act of 2022, which calls for accelerated approval to automatically expire after a specific period of time unless the FDA can confirm that approval is warranted.

However, with the end of the legislative session and a new Congress being seated early next year, and the House changing hands from Democrats, who proposed the bill, to Republicans, it is unclear whether the legislation will proceed.