Ozva AdminBut FDA experts and others said the data doesn’t support that view. In closing arguments, Peter Stein, director of the Office of New Drugs at the FDA’s Center for Drug Evaluation and Research, agreed on the urgent need for a drug to reduce the incidence of premature birth, one of the leading causes of infant mortality in the United States. But he said the data indicates Makena is not that drug.
“Hope is a reason to keep looking for options that are effective,” he said. “Hope is not a reason to take a drug that has not been shown to be effective or to keep it on the market.”
The recommendations of the independent advisory panel are not binding, although the agency generally follows their advice. Removing a drug from the market is a very unusual step.
The three-day hearing was an emotional one for both members of the public and members of the Advisory Committee on Obstetrics, Reproduction and Urologic Medicines.
Several health groups supported keeping Makena on the market while more studies are done, concerned that removing it could deepen racial health disparities. “We believe that removing access will have a detrimental impact on the health of women and birth givers at risk of recurrent preterm birth and will not affect all women equally,” said Martha Nolan, senior policy advisor for HealthyWomen. , a nonprofit reproductive health group focused on helping women make informed decisions about their care.
Members of the panel, which is made up of maternal health experts, neonatologists, statisticians and other experts, recounted their distress over data from a large trial of Makena that showed no benefit for the drug when there are no good alternatives for women with high risk. to deliver early.
“I’m so disappointed. … I wish we weren’t sitting here today,” one member said.
Another, Esther Eisenberg, a reproductive endocrinologist, said she 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 City who was the only member of the panel to argue that the large clinical trial held promise for some subgroups of patients and who voted to keep the drug on the market, said that she was concerned about the underrepresentation of minority women on trial, as “we know that race is kind of a proxy for racism and all structural inequalities.”
Drugmaker Covis Pharma and its sponsors have argued that the study may have lost its benefit in high-risk populations in the United States because the participants were mostly Eastern European and only 7 percent black. in a presentation With the FDA, the drug company called the latest trial “flawed,” not only because of its racial demographics, but also because the population was low risk and women had access to national health care systems that differ greatly from those complex fragmented systems. system in the United States.
Raghav Chari, chief innovation officer at Covis Pharma, had testified that the company was willing to work with the agency to limit the use of Makena to only “a higher risk target population” and would also agree to stop active promotion of the drug. .
He called this a “practical approach” that would allow individual doctors, in consultation with their patients, to make decisions about whether use of the drug might be helpful.
“We are not proposing that race biologically differentiates patients,” he said Wednesday. “At the same time, it is well documented that preterm birth disproportionately affects black and other minority women in the United States. These and other social determinants of risk are factors in defining the highest-risk population in which Makena is most likely to be effective.”
But Joseph Alukal, a urologist who is director of men’s health at NewYork-Presbyterian/Columbia University Irving Medical Center, suggested that the racial inequality argument “implies that the drug is effective and implies that the drug is safe” when in fact We don’t have an answer on what.
Makena was approved by the FDA in 2011 under an accelerated approval program for drugs that treat serious conditions for which there are no treatments. Drug manufacturers are then required to conduct studies confirming the drug’s benefits in order to continue selling the drug. But the debate over the effectiveness of Makena more than a decade after its approval underlines the complexities of that program, highlighting how it can take years for the agency to remove a drug from the market even if officials believe it is ineffective.
In the case of Makena, the FDA’s Center for Drug Evaluation and Research proposed withdrawal of the market in October 2020, a move that followed a 9-7 vote by an expert advisory panel past year 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 limited use “would change the intent of the fast track.” He argued that “in the absence of evidence of effectiveness, we are left only with risk. The benefit-risk balance for Makena is not favorable”.
Francesco Tallarico, head of policy and government affairs at Covis, said the company was “obviously very disappointed” with the advisory committee’s vote. The company will “continue to have a dialogue” with the FDA before making decisions about whether to move forward with a new randomized controlled trial, he said.
The FDA’s decision will not come immediately. Within 45 days of the publication of the hearing transcript, the meeting chair, Celia M. Witten, deputy director of the FDA’s Center for Biological Evaluation and Research, will publish a report on the panel’s recommendations that also contains their own views.
Then the evaluation and research center and Covis will have 45 days to comment. Later, FDA Commissioner Robert Califf and the agency’s chief scientist will review the information and make a decision, which they “plan to make … quickly,” said FDA spokeswoman Shannon Hatch.
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