Advisers to the Food and Drug Administration gathered Monday to begin a high-stakes review of a controversial drug for preterm birth that the regulator wants to remove from the market.
The medicine, called Makena and sold by the private equity-backed Covis Pharma, has been approved since 2011 on a conditional basis. But a 2018 trial failed to show that treatment could prevent premature delivery or reduce newborn mortality, leading the FDA to propose withdrawing the drug’s approval.
Over the next three days, a committee of 16 obstetricians, gynecologists and other experts will hear arguments from both the FDA and Covis, leading to a series of votes Wednesday on the clinical trial evidence supporting Makena and whether the drug should remain available.
The meeting is structured somewhat like a trial, with FDA presenting its case Monday and representatives from Covis set to ask clarifying questions of the agency. The order will be reversed Tuesday, with Covis presenting and the FDA cross examining the drugmaker. Advisers will be allowed to make questions of both each day.
For the FDA, the meeting is a key test of its power to withdraw “accelerated” drug approvals after confirmatory trials fail, and comes as that process has fallen under significant scrutiny by lawmakers, academics and a federal watchdog.
In documents made available ahead of the meeting, the FDA made clear its many concerns with Makena and argued that failing to withdraw it would “undermine” accelerated approvals.
Patrizia Cavazzoni, head of the FDA’s main drug review office and an influential agency leader, reiterated that position in opening comments at the meeting Monday. "Based on the evidence available today, Makena is not shown to be effective, its benefit-risk profile is unfavorable, and it should be withdrawn from the market,” said Cavazzoni.
Covis has pushed back on the FDA’s views, writing in documents that a withdrawal is neither necessary nor appropriate. Instead, the drugmaker argues the medicine — which, along with its generic equivalents, is currently the only treatment option to reduce the risk of preterm birth — should remain available while it conducts another study.
The company has also proposed narrowing the drug’s labeling to include only women at highest risk of premature delivery. In the initial study that supported Makena’s accelerated approval, many of the participants were Black women, who in the U.S. are more likely to experience preterm birth. In the confirmatory study, far fewer were — a difference, among several others, that the company claims makes the confirmatory trial “incapable of measuring the efficacy of Makena.”
While the FDA acknowledges the impact preterm birth has on at-risk women and their children, it disagrees with Covis’ conclusions. “The evidence does not show that this — or any — subset of Makena’s indicated population responds more favorably to Makena than any other subset,” agency staff wrote.
The regulator also expressed doubts that another study could be completed quickly. Notably, the negative results from Makena’s confirmatory study were delivered more than five years after the original agreed-upon timeline, according to a recent report from the U.S. Department of Health and Human Services inspector general.
During that time, Covis and the drug’s original owner, Amag Pharmaceuticals, made significant amounts of money on Makena sales — $700 million between 2018 and 2021 from Medicare and Medicaid alone.
Covis has proposed conducting a randomized clinical trial of about 400 participants, which it estimates would take between four to six years to complete.
While the FDA’s advisers will deliver a vote at the end of the three-day meeting, the agency is not required to follow their advice. FDA Commissioner Robert Califf and agency chief scientist Namandjé Bumpus will make a final decision on Makena’s withdrawal, according to the Pink Sheet.
Jonathan Gardner contributed reporting.