Put simply, the FDA believes there is no evidence that the drug works. Approvals for generic versions of Makena also were revoked.
The decision, which was not a surprise, marks the culmination of a protracted process that began in 2020 when the FDA’s drug center proposed removing the drug from the market. A month ago, Covis Pharma, the Luxembourg manufacturer of Makena, announced it would voluntarily stop selling the drug. That followed a recommendation from FDA’s outside experts last fall that the drug be pulled.
But the company was hoping for what it called an “orderly wind-down” that would allow patients to complete their 21-week courses of treatment and the company to use up its remaining inventory. The FDA’s action Thursday, effective immediately, means that Makena and its generic versions “are no longer approved and cannot lawfully be distributed in interstate commerce,” the agency said.
The FDA said some supplies of Makena have been distributed to doctors’ offices and pharmacies, and that some health-care providers might continue to prescribe or administer the drug. But it urged providers to “consider FDA’s conclusion that these drug products are not shown to be effective for the indication for which they were approved and do not have benefits that outweigh their risks to patients.”
Preterm birth, which is birth before the 37th week of pregnancy, is a heartbreaking and costly health issue in the United States. About 1 in 10 babies arrive too soon, risking lifelong complications and death. Black newborns are more than twice as likely to die as White newborns. The cause of preterm birth is unknown.
The debate about the fate of Makena has evolved in recent years into a complicated swirl of racial and medical considerations.
Makena, which was approved in 2011, is a synthetic version of the hormone progesterone, which is needed to maintain a pregnancy. The agency cleared the drug by accelerated approval because a 2003 clinical trial showed the medication lowered the risk of preterm birth, suggesting it would improve the health of the baby.
The drug was approved for women who had experienced a preterm singleton birth — one that does not involve twins or other multiples. The weekly treatment was begun between weeks 16 and 20 of pregnancy and continued until the 37th week or delivery, whichever came first, according to the label.
But in 2019, a required follow-up trial showed that the drug benefited neither mothers nor babies. In October 2020, when the agency’s drug center proposed that Makena be taken off the market, Covis opposed the move, triggering a lengthy review that became more protracted because of the coronavirus pandemic.
Covis, which is owned by private equity firm Apollo Global Management, argued that yanking the drug would hurt Black women, and that the larger trial was flawed because it did not have a significant proportion of Black patients. It wanted to conduct another trial to prove its point. Some Black health groups also supported keeping the drug on the market.
But critics of the drug, including Adam C. Urato, a maternal-fetal medicine specialist in Framingham, Mass., dismissed that argument as “racial equity spin.” In an opinion article in Stat, an online medical publication, last September, Urato wrote: “How does keeping Makena on the market — so pregnant Black women can disproportionally be injected with an ineffective drug — improve racial equity in any way?”
Last fall, 15 outside advisers to the FDA voted unanimously that the drug did not help mothers or babies and all but one said it should be removed from the market. Covis then offered its “wind-down” plan. But the FDA drug center wanted an immediate withdrawal, so the issue went to the FDA commissioner and the agency’s chief scientist, Namandjé Bumpus.
At the hearing of FDA advisers last fall, Patrizia Cavazzoni, director of the agency’s Center for Drug Evaluation and Research, said that allowing the drug to stay on the market would expose those who are pregnant to serious risks — side effects include blood clots, allergic reactions and depression — without evidence of benefit.
Covis did not respond immediately to a request for comment. The company, in a letter to Califf last month, said it “continues to believe in Makena’s favorable benefit-risk profile, including its efficacy in women at highest risk of preterm birth.”
Before Makena was approved, pharmacists sometimes made their own versions by compounding drugs that included the active ingredient, hydroxyprogesterone caproate.
The agency noted Thursday that drugs containing that ingredient may be compounded legally if certain conditions are met. But it cautioned health-care providers to be aware of FDA’s views on Makena. The agency also noted that compounded drugs, including ones containing hydroxyprogesterone caproate, do not undergo FDA premarket review for safety, effectiveness or quality.
Makena is often held up as an example of flaws in the FDA’s accelerated approval process. The required confirmatory trial should not have taken eight years to complete, critics say.
Ariana Eunjung Cha contributed to this report.