Peter Stein, director of the Office of New Drugs at the FDA’s Center for Drug Evaluation and Research, acknowledged in closing arguments clinicians’ arguments about the need for an effective drug to reduce the incidence of preterm birth – a leading cause of infant death in the United States. He said the agency agrees with clinicians who testified through three days of hearings about the urgent need for such a drug, but only if the data and science back it up — and it doesn’t. is not the case for Makena.
“Hope is a reason to keep looking for options that work, whether we find them here or elsewhere,” he said. “Hope is not a reason to take a drug whose effectiveness has not been demonstrated. or keep it on the market.
The recommendations of the panel of independent advisors are not binding, although the agency generally follows its advice. Removing a drug from the market is a very unusual step.
The three-day hearing was emotional for both members of the public and members of the Obstetric, Reproductive and Urological Drugs Advisory Committee.
Several health groups have backed keeping Makena on the market while further study is underway, fearing its removal could worsen health inequities. “We believe that removing access will have a detrimental impact on the health of women and those giving birth at risk of recurrent preterm births and will not impact all women equally,” said Martha Nolan, Senior Policy Advisor at HealthyWomen, a nonprofit women’s health group focused on helping women make informed decisions about their care.
Members of the panel, made up of maternal health experts, neonatologists, statisticians and other experts, recounted the difficulty of their decision.
“I’m so disappointed… I wish we weren’t sitting here today,” one member said. Another expressed ‘deep sadness’ over Makena’s big trial which showed no benefit.
Esther Eisenberg, a reproductive endocrinologist, supported withdrawing the drug, “but I’m very conflicted. This is a very, very difficult question.
Cassandra Henderson, a maternal-fetal medicine specialist in New York, who was the only panel member who argued that the large clinical trial held promise for certain patient subgroups and who voted to keep the drug on the market, said she was concerned about the low representation of minority women in the trial because “we know that race is kind of a surrogate for racism and all of the structural inequalities.”
Drugmaker Covis Pharma and its funders argued that the study may have missed its benefits in high-risk populations in the United States because participants were largely from Eastern Europe and only 7% black. In a deposit with the FDA, the drug company called this latest trial “flawed,” not only because of its racial demographics, but also because the population was low-risk and women had access to differing national healthcare systems. greatly from the complex piecemeal system in the United States.
Raghav Chari, chief innovation officer at Covis, had said the company was willing to work with the agency to limit the use of Makena to “a high-risk target population” only and would also agree to stop active promotion. of the drug.
He called it a “hands-on approach” that would allow individual doctors, in consultation with their patients, to decide whether using the drug might be helpful.
Chari said Covis is committed to conducting additional studies to answer questions about the drug’s potential risks and benefits, noting that reducing preterm births is a public health priority and an area of unmet need in development. of drugs.
“We are not proposing that race biologically differentiates patients,” he said Wednesday. “At the same time, it is well documented that preterm birth has a disproportionate impact on black and other minority women in the United States. These and other social determinants of risk are factors that help define the population at high risk where Makena is most likely to be effective.
But Joseph Alukal, a urologist who is director of men’s health at Columbia/NewYork-Presbyterian, suggested that the racial inequality argument “implies that the drug works and implies that the drug is safe” when we we don’t have an answer on this.
Mark Hudak, a neonatologist at the University of Florida College of Medicine, said he was “sensitive to the disparity issues that have been raised.” However, he said allowing Makena to remain in the market was not appropriate and would lead to “complete regulatory chaos”.
Makena was approved by the FDA in 2011 under an accelerated approval program for drugs that treat serious conditions for which there is no cure. Drug manufacturers are then required to conduct studies confirming the drug’s benefits to continue selling the drug. But the debate over Makena’s effectiveness more than a decade after its approval highlights the complexities of this program, pointing out that it can take years for the agency to withdraw a drug from the market even if officials think it is ineffective.
In Makena’s case, the FDA’s Center for Drug Evaluation and Research proposed to withdraw from the market in October 2020 – a decision that followed a 9-7 vote by an expert advisory group one year earlier to withdraw it from the market based on the disappointing results of a large confirmatory study. But regulatory requirements, as well as the pandemic, have slowed the process.
The FDA’s Stein argued that leaving Makena on the market for restricted use “would reverse the intent of the fast track.” He argued that “in the absence of evidence of efficacy, we are left with only risks. The risk-benefit ratio for Makena is not favourable.