The maker of a controversial drug for preterm birth has decided to withdraw the hormonal treatment, bringing to an close a lengthy battle with the Food and Drug Administration over its continued use.
In a letter to FDA officials dated March 6, the company, Covis Pharma, said it would voluntarily remove the drug from the market, and requested time from the agency to “wind down” its commercial operations.
Covis’ decision follows years of debate over the drug, called Makena and approved in 2011 for the prevention of early labor. Its continued clearance was in substantial doubt after a meeting last October of FDA advisers, who recommended for the second time that it be withdrawn.
“While we stand by Makena’s favorable benefit-risk profile, including its efficacy in women at highest risk of preterm birth, we are seeking to voluntarily withdraw the product and work with the FDA to effectuate an orderly wind-down,” said Raghav Chari, Chief Innovation Officer at Covis, in a statement.
In moving to withdraw Makena, Covis is acting ahead of a final decision, expected soon, from FDA Commissioner Robert Califf and Chief Scientist Namandjé Bumpus.
A memo filed Wednesday by the FDA’s Center for Drug Evaluation and Research, which oversees Makena’s approval status, recommended an immediate removal from market. “The legal standard for withdrawal has been met, and Makena should be withdrawn,” the memo said.
In an email, an FDA spokesperson noted the center’s decision remains pending until a decision by the commissioner’s office. “However, Covis may remove its product from the market or withdraw its application on its own initiative.”
Makena’s 2011 approval was based on a trial run by the National Institutes of Health that showed the drug, a synthetic hormone called hydroxyprogesterone caproate, helped prevent early labor in women with a prior history of delivering before full-term. But its clearance was conditional on further study proving its benefit
Results from that confirmatory trial, released in 2019 and long after they were originally due, showed Makena didn’t prevent preterm births or improve the health of newborns. An advisory committee later recommended removing the drug from market and, one year later, FDA staff proposed its withdrawal.
But Covis, which had acquired the drug’s prior owner Amag Pharmaceuticals, called for another hearing to dispute the FDA’s proposal, leading to the second meeting last October.
Following three days of testimony and debate at that meeting, the FDA’s advisers voted 14-1 to recommend Makena’s withdrawal. Final documents from both Covis and the overseeing FDA department had been due March 6, after which Califf and Bumpus were to make their final decision.
As the regulatory process has played out, Makena has continued to be marketed and prescribed to patients. Prior to the negative results from the confirmatory trial, annual sales of the drug regularly reached into the hundreds of millions of dollars.
Preterm birth, usually defined as before 37 weeks of gestation, increases the risk of disability or death of the baby. While it is associated with many different risk factors, it occurs more frequently in Black women.
There are no other approved medicines to prevent preterm birth, a fact Covis used in its argument to keep the drug available while it conducted further testing. The company also cited Black women’s higher risk of preterm birth, raising questions about equitable access to care.
“[R]etaining approval of a drug simply to be able to offer something to patients, regardless of effectiveness, would be contrary to public health,” CDER, the FDA office, wrote in its memo.
The controversy over Makena has taken place as the FDA’s accelerated approval process has come under fire. Drugmakers are often slow to complete the required confirmatory testing, leading to doubts about how much some medicines actually help patients. The agency has increased scrutiny of these “dangling” approvals in recent years, particularly of cancer immunotherapies, leading to withdrawals from several large pharmaceutical companies.
Editor’s note: This story has been updated with emailed comment from an FDA spokesperson.