FDA staffers pull no punches on Makena as Covis' preterm birth drug faces expert panel reckoning

When a long-awaited FDA hearing over Covis Pharma’s recurrent preterm birth drug Makena kicked off Monday, the agency paraded out a half dozen of its experts to convince the panel it should recommend withdrawal of the medicine.

More than a decade after Makena's accelerated approval in 2011, Covis has failed to prove its effectiveness, officials from the FDA’s Center for Drug Evaluation and Research (CDER) said. That gives the agency a strong case for the drug’s removal from the U.S. market, they added. The remarks formed part of an opening salvo at this week’s meeting of the agency’s Obstetrics, Reproductive and Urologic Drugs Advisory Committee, which is due to help decide Makena’s fate by Wednesday.

Makena’s reckoning comes after the FDA urged the drug be pulled from the market back in 2019. Last August, the FDA said it would give Covis a chance to plead its case for Makena and the med’s five generic counterparts, which make up the entire armamentarium available to reduce the risk of recurrent preterm birth in women who have a history of spontaneous preterm birth.

That unmet need added fuel to Makena’s accelerated approval back in 2011, which the FDA granted based on positive findings from the 463-subject Meis study, also known as Trial 002.

But the United States’ accelerated approval pathway is a “two-way street,” CDER’s Sara Rothman, J.D., M.P.H., said near the top of the advisory committee meeting.  

“The balance of approvals and withdrawals are needed to make the program work, and thereby protect patients and public health,” she added.

In the time since Makena’s original nod, Covis ran another study, dubbed Prolong, in a bid to prove its med’s worth. That trial failed to verify the drug’s clinical benefit on neonatal morbidity and mortality from complications of preterm birth, the FDA said.

Makena’s 2019 confirmatory trial results were “extremely disappointing,” Christina Chang, M.D., M.P.H., the acting director of the FDA’s division of urology, obstetrics and gynecology, said at Monday’s meeting.

"Not only did treatment with Makena fail to reduce neonatal mortality and morbidity, it also failed to reduce preterm delivery prior to 35 weeks gestational age," Chang said.

Even after taking a deeper dive into data from both Meis and Prolong, which also goes by the name Trial 003, the FDA found “Makena has not been shown to be effective,” with “substantial evidence” of its benefit “lacking," the agency said in conclusion.

Covis, for its part, says it’s fully onboard with running additional trials “and executing a robust plan” to satisfy uncertainties around its drug. The company acquired Makena after the FDA vouched for its withdrawal in 2019 and became its “sponsor” in 2021, Covis said in arguments prepared ahead of Monday’s AdComm meeting.

The company stressed that preterm birth is a public health concern, noting its disproportionally affects women who are Black, plus other minorities or people are socioeconomically disadvantaged.

To satisfy the FDA’s concerns, Covis recommended a number of possible solutions, such as a partial withdrawal to a higher-risk target population. The company would also pledged not to actively promote the drug.

Further, Covis floated the possibility of another randomized trial on Makena with a 4-6 year run time, plus an optional observational study.

The hearing only started on Monday morning, and experts were still set to review the drug's data through midday Wednesday. In the end, the committee will be asked to answer three questions on the med's data and whether it should remain on the market.