After 11 years at large, Makena’s accelerated approval odyssey seems destined to end in exile.
Wednesday, an FDA panel of outside experts voted 14-1 to pull Covis Pharma’s swiftly approved preterm birth med from the market, pointing to the failure of its 2018 confirmatory trial PROLONG to show Makena helped prevent death or health complications in newborns whose mothers received the drug.
The FDA doesn’t have to follow its experts’ counsel, though it often does. And, in this instance, the agency’s been making its intention to pull Makena known for some time.
As for Covis, the company "will work collaboratively with the FDA to clarify the next steps in this process,” Raghav Chari, Ph.D., Covis’ chief innovation officer, said in a company statement issued after Wednesday’s vote.
The vote comes more than a year after the FDA's accelerated approval of Biogen's ill-fated Aduhelm put a spotlight on the regulatory pathway, which is designed to speed treatments to patients with few options. One caveat of the program is that drugs must prove their worth in a confirmatory trial, which Makena failed to do.
The agency’s speedy approval pathway is a “two-way street,” the FDA’s Sara Rothman said Monday as the agency’s Center for Drug Evaluation and Research made its case against Makena. “The balance of approvals and withdrawals are needed to make the program work, and thereby protect patients and public health,” she added.
The regulator first suggested the drug be pulled from the market back in 2019. In a separate advisory committee in 2020, panelists voted 9-7 to recommend the drug’s removal.
But Covis acquired Makena after the FDA vouched for its withdrawal and became its regulatory “sponsor” in 2021. Last August, the FDA granted Covis’ request to fight for Makena before another expert panel.
Early this week before the panel’s vote came in, Covis said it was game to run additional trials and hash out a plan to quell uncertainties around its drug.
One solution proposed by Covis was a partial withdrawal to certain patients coupled with a pledge not to actively promote the drug.
“As presented during the hearing, we believe that Makena is effective in a higher-risk patient population,” Chari added in his statement.
Covis also suggested it could run another randomized trial within a four- to six-year time frame, plus an observational study.
While the Makena saga appears to near to a close, bigger questions surrounding the FDA’s accelerated approval pathway remain. In fact, Congress had been weighing changes to the program that would give the agency more power, though lawmakers punted on any sort of reform when they sparred over a must-pass FDA bill last month, Axios reported.
Meanwhile, just this week, FDA Commissioner Robert Califf, M.D., stressed that accelerated approval reforms are needed “as soon as possible.”
“While the process is intended to ensure the integrity of the data and analyses, the fact is that accelerated approvals based on biomarkers leave more uncertainty about the true risk and benefit,” Califf said in speech Monday at the National Organization for Rare Disorders’ annual conference.