Makena Saga Shows How Hard It Is to Remove Unproven Drug from Market

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Even after an FDA advisory panel voted 14–1 in October 2022 to remove the drug, Makena manufacturer Covis Pharma continued to press for some continued access to the therapy.

After more than a decade of delay tactics, it appears that FDA may finally bring about the withdrawal of its earlier approval of the controversial drug to prevent preterm birth. Even after an FDA advisory panel voted 14–1 in October 2022 to remove the drug, Makena manufacturer Covis Pharma continued to press for some continued access to the therapy. In a long submission, the firm’s attorneys argued that the weak trial results were inconclusive and that more studies should be done, and that there is no other drug available to prevent preterm birth, so Makena is better than nothing.

Officials at the Center for Drug Evaluation and Research (CDER) disagreed, stating that it undermines public health to offer a drug to patients that offers only risks and no benefits and that Makena should exit the market immediately. FDA explains that Makena was approved under the accelerated approval process, but that postmarketing clinical studies had failed to confirm its effectiveness in reducing the risk of premature birth in its target patient population. Therefore, CDER analysts urge Commissioner Rob Califf and the agency’s chief scientist, who are charged with deciding the issue, to support immediate withdrawal of the drug and any generic versions to avoid exposing patients to further risk. And in specific response to Makena’s proposal to continue treatment for those patients already using the drug, agency experts emphasize that there is no evidence of patient harm from discontinuing Makena, and only further risks from continued treatment.

The 12-year Makena saga illustrates how difficult it is for FDA to cancel marketing of an approved therapy, even when test data fails to confirm efficacy, and the need for reform of the accelerated approval process to ensure patient use of effective treatments. An FDA advisory committee that met in October 2019 was divided on whether to withdraw the drug. Even though postapproval studies of Makena by then-manufacturer AMAG Pharmaceuticals failed to confirm substantial evidence of effectiveness, some panel members supported leaving the product on the market pending further evidence. The company objected to additional trials, and FDA proposed to remove the drug from the market in October 2020.

That led to the more recent advisory committee meeting in October 2022. With little new evidence to support the drug’s efficacy, this time the panel voted unanimously that a confirmatory study showed no benefit, and it agreed 14–1 to remove Makena from the market. Covis initially objected to that course of action and sought to continue to make the drug available to very high-risk patients. Only when FDA issued a much harsher report this month did the company agree on March 7, 2023 to “voluntarily withdraw the product” in an “orderly wind-down,” said Covis Chief Innovation Officer Raghav Chari.


Just how long that “wind-down” takes remains to be seen. Covis continues to point to the lack of any alternative treatment to prevent miscarriage, and that that some treatment—even its ineffective one—is better than nothing. And the company has highlighted the higher rates of miscarriage among black women, and that removing the drug discriminates against this minority patient group.

FDA and the research community, however, recognize that it’s impossible to conduct any placebo-controlled study if any approved treatment is available to patients. Leaving the drug on the market all these years now is seen as a deterrent to developing more effective therapies for this condition. But the therapy generated some $1.5 billion in sales since its approval in 2011, according to press reports. If Califf and his staff agree with CDER’s recommendations, the marketing of Makena may finally end.

About the author

Jill Wechsler is Washington editor for BioPharm International.