On Thursday, the US Food and Drug Administration announced its final decision to withdraw its approval of Makena, a drug approved more than a decade ago to reduce the risk of preterm birth that had been the only medication approved for the condition.
The FDA says that the drug is not effective and that the benefits of taking it do not outweigh the risks.
“It is tragic that the scientific research and medical communities have not yet found a treatment shown to be effective in preventing preterm birth and improving neonatal outcomes – particularly in light of the fact that this serious condition has a disparate impact on communities of color, especially Black women,” FDA Commissioner Dr. Robert Califf said in a statement. “Fundamentally, however, the touchstone of FDA drug approval is a favorable benefit-risk assessment; without that favorable assessment, the drug should not have the status of being FDA-approved.”
About 1 in 10 infants born in the US are preterm, before 37 weeks of pregnancy. The lungs and brain finish developing in the last few months of pregnancy, and preterm birth places the baby and the mother at higher risk of death and disability.
The condition disproportionately affects Black women, for whom the rate is about 50% higher than the rate for White or Hispanic women, the US Centers for Disease Control and Prevention says.
Preterm birth has also been a growing problem in the US. The CDC says the rate rose 4% from 10.1% in 2020 to 10.5% in 2021.
Before Makena, there were no reliable medication options for these patients, so it went through the FDA’s accelerated approval process.
That process is used when there’s no reliable treatment for a condition and a drug shows promise in clinical trials. The FDA created it in the height of the AIDS epidemic, when people were dying in record numbers with no options. Accelerated approval means a drug doesn’t have to go through all the levels of testing in humans that are required for the standard approval process.
Makena was approved in 2011 for women who have a history of spontaneous preterm delivery after a clinical trial showed a reduction in the rate of preterm births but no direct clinical benefit.
One condition of accelerated approval is that, even after the drug hits the market, the company must continue to test it in people to make sure it works.
In the years since Makena was approved, drugmaker Covis says, about 350,000 women have been treated with it. But a large 2019 study failed to show that it actually prevented preterm birth.
In October 2020, the FDA’s Center for Drug Evaluation and Research met to take a closer look at the research, and it recommended that the FDA withdraw approval for the drug.
The drug and its generic equivalents were allowed to remain on the market until the manufacturer removed them or the FDA commissioner mandated removal.
In October, the FDA’s Obstetrics, Reproductive and Urologic Drugs Advisory Committee voted that Makena should not remain on the market. It also voted that a postmarket trial didn’t show any benefit to babies and that the evidence didn’t show that Makena reduced the risk of preterm birth in women who had had one before.
Last month, Covis said it was moving to withdraw the medication from the market.
Covis said that soon after the committee hearing, it outlined a plan for withdrawal that included a wind-down period allowing patients to finish the 21-week course of treatment. However, the Center for Drug Evaluation and Research rejected the plan.
“While we stand by Makena’s favorable risk-benefit 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,” Covis Pharma Chief Innovation Officer Dr. Raghav Chari said in a news release at the time.
Effective Thursday, the FDA says, Makena and its generics are no longer approved and cannot lawfully be distributed in interstate commerce.
The FDA said that although the approvals of Makena and its generics have been withdrawn, it recognizes that a supply of product has been distributed. It said patients who have questions should talk to their health care provider.
Dr. Sean Blackwell, chair of the Department of Obstetrics, Gynecology and Reproductive Sciences with UTHealth Houston, said he understands that the FDA does not want to expose people to risk or to unnecessary cost, but he disagrees with the interpretation of the research and the decision to withdraw the drug from the market.
“I certainly have had some women that had a prior preterm birth, and then I put them on Makena and had good outcomes. So for those patients, they’re going to be distressed that they used a medication and it worked for them, and now it’s no longer available,” he said.
There are no good options, he said.
“Doctors are going to want to do something. They’re not going to just be OK with saying, ‘there’s nothing we can do. We’ll just sit on our hands,’ ” Blackwell said.
The other medication alternative is vaginal progesterone, he said, but trials have shown that it is not necessarily effective, either.
Doctors may have to rely on surgical approaches to prevent preterm birth, “but it’s surgery. It has side effects. It has risks,” Blackwell said. “I do think that going forward, it’s going to be really hard.”