An advisory committee of the Food and Drug Administration on Wednesday recommended that Makena be removed from the market, after years of research showed the fast-track drug did not prevent premature birth.
Makena has been in use for 11 years, and the jury vote is very broad be seen as a test part of the agency’s “expedited approval” program, which has brought nearly 300 promising drugs to market in 30 years. The program has been criticized for leaving many of the drugs in use as follow-up studies drag on to determine if they are effective. The program has attracted considerable attention beyond consent of the Alzheimer’s drug Aduhelm last year, an expensive drug that many experts consider unproven.
It is the first time in more than a decade that the agency, often following the advice of expert panels, has shown a willingness to force a drug maker to stop selling a fast-track product.
The move to pull Makena off the market – the only drug approved to prevent premature birth – has been combined with emotional appeals and issues about racial and health disparities. The risk of preterm birth is much higher for Black women, a point that Covis Pharma, the maker of the drug, has pressed in a protracted effort to take its case to the FDA.
According to the Centers for Disease Control and Prevention, premature birth, defined as born before 37 weeks of pregnancy, one in 10 US infants will be affected in 2020. But the agency notes racial and ethnic disparities: At the same time, The preterm birth rate among African-American women (14.4 percent) is about 50 percent. higher rates of preterm birth in white or Hispanic women (9.1% and 9.8%), respectively.
If the agency followed the panel’s recommendation and placed the drug on the market, patients who were born prematurely and faced a second attempt would not receive an approved treatment (although Covis may continue to do so). research on this drug).
Annie Ellis, a patient representative on the panel from White Plains, NY, who recommended removing the drug on Wednesday, said the situation is dire.
She told the committee: “It is painful that nothing will be available in 2022 in the United States of America. “The inequalities that exist and the morbidity of babies – for mothers, it just hurts on so many levels.”
The advisory committee weighed in on three separate votes on Wednesday. All 15 of voting board members agreed that lengthy post-marketing trials showed no benefit to infants. 13 also agreed that the drug has not been shown to be effective in reducing the risk of preterm birth in women who have had one preterm birth. Fourteen agreed that the drug should be withdrawn from the market.
After voting to eliminate the drug, Dr Anjali Kaimal, an obstetrician and administrator at the University of South Florida, admitted it was “horrifying” to tell a patient that there was no cure. treatment for a serious condition. But “additional research is needed,” she said. “I want to believe that there is a solution to premature birth.”
Makena was approved on a conditional basis in 2011 after it emerged to help mothers carry full-term babies – a factor believed to reduce infant mortality and disability. The company says 350,000 American women have used it in the past decade. After years of follow-up studies, the drug was no more beneficial for infants than placebo.
Usually, drug manufacturers quietly withdraw the drug after such a failure. However, Covis Pharma, which is owned by the private equity firm Apollo Global Management, has appealed to the agency allowing it to continue to market the drug to a shrinking group of high-risk women. , and promised to stop advertising the drug and conduct research again.
Raghav Chari, chief innovation officer at Covis, said during the company’s presentation on Tuesday: “A complete recall of the product would harm patients who are most at risk of preterm birth. “We are proposing the best course of action for women and their unborn babies.”
He also warned that even if the FDA pulls the drug back, it could still be made available at specialty compounding pharmacies, which have a track record of sterility and contamination problems.
After the vote, Francesco Tallarico, Covis’ chief adviser, said the company would send additional information to the agency. He said it’s too early to say whether the company will conduct further research on the drug.
“We are very disappointed with today’s results,” Mr. Tallarico said. “Our intention is and is to do what is best for the patient.”
During a three-day hearing this week, agency officials argued with Covis, citing their shift from hope to disappointed that the drug would help an infant at risk of death or lifelong health problems.
“We thought Makena could be part of the answer to that,” said Dr. Patrizia Cavazzoni, director of the agency’s drug division. “Unfortunately, we no longer do.”
In one prepared summary For the hearing, the FDA said not recalling the drug “would be detrimental to patients” at risk of preterm birth “and would undermine the faster approval process.” The agency also notes that the drug carries a risk of blood clots, depression and allergic reactions.
Dr. Namandjé Bumpus, the FDA’s chief scientist, and Dr. Robert Califf, the agency’s commissioner, will make a final decision in about 90 days.
Among those who testified in support of Covis’s call was Dr. Washington Hill, a black mother-fetal specialist in Florida. After the vote, Dr. Hill said he had hoped for a different outcome but saw a positive one: Panel members all endorsed the incredible need for “Black, Skin” patients brown and vulnerable” are at high risk of being treated effectively.
“We need companies to do that,” Dr. Hill said. “Companies may not be willing to go down this path again. They may not. “
There is no approved treatment, Dr. Hill said doctors only have therapy for women who give birth prematurely. He said they can also prescribe bed rest, although there is little evidence that it works.
The NAACP also weighed in before the hearing with a letter calling on advisors to pay attention to other advocacy groups that said withdrawal could “deepen deep inequalities in maternal health and babies in America”
The hearing has been widely compared to another hearing in 2011, when advisors considered whether to keep Avastin on the market for breast cancer. It was also approved under the accelerated route, and subsequent research showed the drug to have risks but little benefit. However, women on medication and cancer survivors filled a hearing room with applause as they make emotional pleas for the agency to keep it on the market.
That hearing was so controversial that advisory committee members – who voted to withdraw the drugs – were escorted out of the hearing by security agents into a waiting fleet of black sedans. Dr. Margaret Hamburg, commissioner of the agency at the time, final decision to obtain drug approval for that use.
The virtual hearing for Makena began Monday without power from an in-person event, with several women asking the agency to research more about the drug via teleconference.
FDA announced its intentions take Makena off the market in 2020, citing failed research on 1,700 women. The company that owned the drug at the time, AMAG Pharmaceuticals, appealed the decision, ending years of wrangling over the details of a hearing that ended on Wednesday.
Delays are lucrative for drugmakers: A recent one government watchdog report estimates that Medicaid, which covers about 40% of births in the United States, has paid out nearly $700 million for Makena courses since the study to evaluate its benefits came due in 2018. The Department of Health and Human Services’ inspector general’s report found that government payers spent a total of $18 billion on approved drugs based on promising findings – but continue to sell on the market after the date they are said to prove beneficial.
The accelerated approval pathway is meant to speed drug sales for deadly conditions and those for which no other therapy is available. Since the program began in 1992, the agency has revoked the approval of 35 drugs for specific uses. Most of those decisions have occurred since last year, when criticism flared over the approval of Aduhelm and the tired drugs without evidence of benefit.
The FDA this year announced “Project confirmation“Focus on the rapid assessment of cancer drugs.
Aaron Kesselheim, a Harvard physician who researched the program, said the decision advisory vote on Makena underscores why Congress should pass giving the FDA more power to expedite research. follow up and remove drugs from the market if they are flawed. .
Maintaining faith in the program “requires swift action in cases like these where the initial hope is gone.”
