FDA’s Accelerated Drug Approvals Under Review

When Brittany Bonds gave birth to her third son in the back of an ambulance 10 weeks before her due date, she no longer trusted the Makena medication.

The drug was aimed at preventing premature birth and improving the health of a baby. But it didn’t work out for Ms Bonds, who had her son Phoenix in the neonatal intensive care unit for 83 days. At 2 years old, he still has a number of health issues.

Makena is another example – like the controversial Alzheimer’s drugs Aduhelm – A drug quickly released by the Food and Drug Administration, although serious doubts remain as to whether it works.

The ongoing debate about Aduhelm’s approval has rekindled interest in the accelerated pathway for drugs to reach market. A invoice Being sponsored by a Republican in Congress would make it even easier for a company to approve a drug and keep it available. Proposed by a leading Democrat, Authorize the FDA to obtain definitive answers on fast-track drugs and remove them from the market if insufficient.

However, any effort to limit the accelerated process will likely draw the ire of the powerful pharmaceutical industry. top US industry Last year, in lobbying spending and spends a lot in political campaigns.

Director of Public Citizen, a nonprofit consumer advocacy organization, Dr. “I think there will be tremendous resistance from the pharmaceutical industry to tightening rules on accelerated approvals,” said Michael Carom.

Questions lingered about Makena for ten years before the big deal was made. study showed the drug had the same effect as the placebo. FDA recommended taking the drug out of market more than a year ago. He plans to hold a hearing on Makena’s fate that will focus on scrutiny over a drug approval process that some critics claim is speeding above the science.

Ms Bonds is one of 13 plaintiffs in the lawsuit against AMAG Pharmaceuticals, the previous owner of the drug, and is seeking the drug’s removal from the market. “It didn’t work for me and I know it didn’t work for others,” she said.

Covis Pharma, which currently owns the drug, plans to challenge the agency’s decision in the upcoming hearing, arguing that Makena has been really effective for the women she initially helped: African American women who are facing some of the highest rates of preterm birth in the developed world.

Premature babies also face the risk of being born dead or disabled. D., a black maternal-fetal medicine specialist in Sarasota, Fla. “There’s a lot of emotion involved in this,” said Washington Hill. He has prescribed the drug to women at risk for decades and was paid $1,200 in counseling fees. He testified in his favor in 2019. “I felt this drug was effective in the patients I worked with,” he said in an interview.

Throughout the life of its accelerated approval program that began 30 years ago, the FDA has had to weigh the passionate, sometimes hopeless gratifications of accessing drugs against the available science-based evidence.

During these decades, the agency has released 278 approvals As of December, within the scope of the program. Approvals do not prove that a drug prolongs survival or improves quality of life. Instead, drugs may be introduced based on a single study with a positive finding (such as tumor shrinkage) and retained if a follow-up study is beneficial.

This pathway to serious conditions and unmet medical needs has given patients earlier access to life-saving medicines; this is a source of pride for industry groups such as the Biotechnology Innovation Organization BIO. A BIO representative told lawmakers Last week, he said he supports a pending plan for drug manufacturers to use real-world evidence to more quickly prove that an accelerated approval drug works. PhRMA, which also represents drug manufacturers, said it supports the program in its current form.

Still, critics and watchdog groups argue that Medicare’s spent billions Even as drug manufacturers are scrambling to complete the necessary follow-up studies that could lead to drug withdrawal if negative, it’s on the subject of accelerated approval drugs. In some cases, fast-track drugs with little benefit remained on the market anyway.

Speeding up science has long worried: FDA heavily criticized For his actions on Vioxx, a pain medication approved under accelerated review later withdrawn On findings in 2004 that it increases heart attacks and strokes. Even more leeway has been given for expedited reviews under the 21st Century Cures Act of 2016.

In the wake of the Aduhelm approval debate, the FDA faces another round of scrutiny next week when the advisory panel is reviewed. a new drug, Amylyx for amyotrophic lateral sclerosis, a fatal neurological disorder. While the drug meets a bar for expedited approval — addressing a serious illness with unmet needs — its manufacturer seeks traditional approval.

As for the current status of expedited approvals, FDA spokesperson April Grant said the agency is working to ensure that drug manufacturers complete follow-up studies on the drugs in a timely manner. Ms. Grant said if she finds gaps in her authority, “then the agency will work with Congress to close those gaps.”

The accelerated program traces its history back to the raucous 1988 protest on the front steps of the FDA, when AIDS emerged. activists raid The organization headquarters was enraged for doing so little as thousands of young men died.

They drew each other’s bodies with sidewalk chalk. The police handcuffed them with zippers and dragged them away.

Mark Harrington, who helped organize the 1988 show, is the executive director of the Treatment Action Group, which advocates for access to medical treatments. He said the rowdy protest sparked controversy to speed up access to new drugs.

While initially promising drugs fell short, in the mid-90s protease inhibitors lowered virus levels and provided a medical miracle.

“All in all, the expedited approval arrangements have worked,” said Mr. Harrington. “They have helped attract more companies to the space. They have led to the discovery of effective treatments.”

Still, Mr. Harrington and others watched with concern as researchers identified accelerated approval drugs with minimal gains for patients.

Of the 253 drugs authorized under accelerated approval since 1992, nearly half – 112 – have not been proven to prolong survival or improve quality of life. according to an investigation In the BMJ, which was published last year. Two dozen drugs have been on the market for five years or more.

another study Of the 93 cancer drug treatments cleared since 1992, 20 percent proved to prolong overall survival, while others remained on the market after follow-up studies showed more modest gains, such as delaying tumor growth. The FDA said overall survival improvement can be difficult to assess as it takes years to achieve.

This study reports that a drug, Avastin, has gained accelerated approval to treat glioblastoma, a brain cancer. While a follow-up study did not show long-term survival or improved quality of life, Avastin still received full approval for this use in 2017.

The same drug was also used to treat breast cancer, and is the only example. FDA revoked Accelerated approval for a single use of a drug despite emotional welcomes for granting permission for cancer patients in 2011.

In 2010, the FDA reversed its decision. Get out Midodrin for patients with dangerously low blood pressure, just one month after it told the drug manufacturer it “could not provide evidence of the drug’s benefit.”

Actually, Makena’s makers that precedent quote arguing that preterm birth medications should remain available. Makena’s manufacturer reminded the FDA: The agency changed course on blood pressure medication “due to concern about increased support for the drug and loss of access.”

The current owner of the drug, Covis, funded a patient group called the Preterm Birth Prevention Alliance, whose members can testify about the drug’s fate at trial.

Makena’s story begins with a medical mystery: Scientists aren’t sure what triggers the birthing process in humans. A tip for prevention emerged in 2003 with results. of a study The active ingredient of the drug is a form of the hormone progesterone.

The study, which included many high-risk Black women, it showed that i saw medicine 34 percent reduction In the risks of giving birth prematurely compared with those in the control group.

an FDA statistical analysis The results of the study concluded that the data “do not provide convincing evidence” of effectiveness. The main concern was when the drug was most effective, when it was started at or before the 18th week of pregnancy, when fetal or neonatal death rates were also “most significant,” according to the report.

Still, the FDA granted accelerated approval to the drug in 2011, and it remains the only drug approved to reduce the risk of recurrent preterm birth. best medical societies that have accepted fund from the drug’s manufacturer approved its use, and Makena was prescribed so routinely that it was difficult to study in the United States.

By 2019, the results of a large study conducted mostly in Europe were available. They suggested that the drug had no effect: The percentage of women who gave birth prematurely while using the drug was about the same as those given a placebo.

The FDA reviewed the data to see if there was a subset of patients in the United States who benefited, including 113 Black women. it I couldn’t find one. FDA in October 2020 announced He wanted to stop using the drug.

The drug’s manufacturer, later AMAG Pharmaceuticals, requested a hearing, partly discussing He said the studies leave open the question of whether his medications benefit high-risk Black women. “Our view is that, given the results of both of these studies, additional research is warranted,” said Francesco Tallarico, general counsel at Covis Pharma.

it’s a concern shared by others A professor emeritus at Harvard’s medical school, Dr. Those with no financial interests, including Michael Greene. She and her colleagues said the second study was “powerless” because it included a small number of Black women.

“Is it really fair and equitable to withdraw a labeled indication for a drug that is beneficial to the few simply because it is not beneficial to the majority?” Associate editor of the New England Journal of Medicine, Dr. said Greene. “It just didn’t seem fair to us.”

Maternal-fetus specialist in Sarasota, Dr. Hill said the drug-related debate is dividing the maternal-fetal medical care community. He wants the drug to remain approved, but is unsure that it will. “My instinctive reaction would be that I would have to have a lot of persuasion.”

Even those who are skeptical of the drug want to know more. “I think more studies need to be done,” said Olivette Bennett, a pregnant woman from Baltimore, who recently stopped taking the drug because she didn’t think it was working. “Where is the voice of African American women who say they work for them?”

in the federal case Against AMAG Pharmaceuticals, Ms Bonds of Missouri, who is white, and other plaintiffs allege that company leaders periodically reviewed the 2019 study, but continued to market the drug as something that could help women. AMAG said the case should be rejected on the grounds that it constitutes an attack on a drug manufacturer’s right to advertise an FDA-approved drug.

In an interview, Ms Bonds said she started taking Makena in each of three pregnancies after a stillbirth in 2011. His first two sons were born at 36 weeks, a few weeks short. full time.

She said she took the drug reluctantly when she was pregnant with her third son. He was depressed because his birth had come first and foremost. He said more studies need to be done before the drug is approved. “I think it would help prevent a lot of false hopes,” Ms Bonds said.