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Three FDA advisors resign from government approval for Alzheimer’s disease treatment

This week, three scientists resigned from an independent committee advising authorities on treatment in a strong statement against the Food and Drug Administration’s approval of Biogen’s controversial drug for Alzheimer’s disease. ..

Dr. Aaron Kesselheim, a professor of medicine at Harvard Medical School and Brigham and Women’s Hospital, submitted his resignation on Thursday after resigning from the committee for six years. ..

He said the agency’s approval of a drug called aducanumab, which is sold as Aduhelm, a monthly intravenous infusion that Biogen sells for $ 56,000 a year, was incorrect. It means that the medicine works. “

The other two members of the committee resigned earlier this week and of the committee Overwhelmingly sorry After reviewing clinical trial data in November.

The Commission did not convincingly show evidence that Aduhelm can delay cognitive decline in people in the early stages of the disease, and that the drug causes potentially serious side effects of cerebral swelling and cerebral hemorrhage. I discovered that there is a possibility. None of the 11 members of the committee considered the drug ready for approval. Ten people voted against it, and one was uncertain.

“Approval of ineffective drugs has serious potential to undermine future research into potential new treatments,” said a neurologist at Washington University in St. Louis, who first resigned. Dr. Joel Perlmutter said. From the committee.

“In addition, the implementation of aducanumab therapy can cost billions of dollars, and these dollars may be used more often to develop better evidence of aducanumab or other therapeutic interventions. “Dr. Perlmutter added.

Shannon P, FDA spokesman. Hatch said the FDA has not commented on issues related to individual members of the advisory board.

Biogen will begin shipping the drug in about two weeks. More than 900 sites across the country, usually memory clinics that see patients with dementia, expect to be ready to take the drug soon.

FDA Decision When it lights up in green, the treatment for Alzheimer’s disease has been approved for the first time in 18 years. Patient advocacy groups were seeking approval because there were only five others. medicine Available for debilitating conditions, they deal with dementia symptoms for only a few months.

But at least since last fall, including some respected professionals Alzheimer’s disease doctor involved in clinical trials of aducanumabSays available Evidence raised serious suspicion About whether the drug is effective. Even if they could delay cognitive decline in some patients, the proposed benefits (delaying symptoms for about 4 months in 18 months) are barely noticeable to patients and are a side effect of the brain. He said it may not outweigh the risks.

Beyond the high price tag of the drug, it is possible to add tens of thousands of dollars to the tab for the additional cost of screening patients before treatment and for the usual MRI needed to monitor their brains for problems. There is sex. Medicare is expected to bear most of the bill.

“Patients are in a very difficult position and doctors are in a difficult position because of the significant risk of needing multiple MRIs at a price of $ 56,000 per year, as well as giving patients ineffective drugs. I’ll be there, “Dr. Kesselheim said.

Beyond their belief that existing evidence of Aduhelm’s interests is weak, resigned advisory board members, and some prominent Alzheimer’s disease experts, oppose two key aspects of the FDA’s approval decision. Did.

One problem is that the FDA has approved the drug for a much wider patient group (people with Alzheimer’s disease) than many experts expected. In clinical trials, the drug was tested only in patients with early stages of Alzheimer’s disease or with mild cognitive impairment.

Another issue was that an important part of the FDA’s rationale for granting approval was the claim that the ability of drugs to attack amyloid proteins in patients’ brains helps delay their cognitive symptoms. about it.

“This is a big problem,” said Dr. Perlmutter.

Amyloid is considered a biomarker for Alzheimer’s disease because its accumulation in the brain is an important aspect of symptoms, but the science that reducing amyloid actually helps alleviate patients’ memory and thinking problems. There is little evidence.

Over 20 years of clinical trials with other amyloid-reducing drugs have failed to provide evidence that the drug has delayed cognitive decline. As a result, many experts have stated that it is especially important to have solid evidence of Aduhelm’s ability to cope with symptoms.

In November, FDA officials told advisory board members that the ability of drugs to reduce amyloid would not be counted as an indication that it could be effective. But with a decision on Monday, the FDA announced that it did exactly that.

“The FDA has determined that there is substantial evidence that Aduhelm reduces amyloid beta plaques in the brain, and that reducing these plaques is quite likely to predict significant benefits to patients,” he said. Dr. Patrizia Cavazzoni, Director of the FDA’s Center for Drug Evaluation and Research, Written on the agency website About the decision to make the drug available under a program called Fast approval..

However, members of the advisory board have never been asked for their views on the authorities’ plans to consider approval based on amyloid reduction and its significant changes. He said he had never been told. Dr. Perlmutter said the committee was “not informed of any additional information or statistical analysis to support” the approval.

Dr. David Knopman, a clinical neurologist at the Mayo Clinic, wrote in an email notifying FDA authorities that he had resigned from the advisory board on Wednesday: I can’t defend. “

Dr. Nopman, who declined the November meeting because he was a field principal investigator in one of the aducanumab trials, added: Mocking of the role of the advisory board. “

Dr. Peterstein, who heads the new pharmacy at the FDA’s Drug Evaluation and Research Center, said with reporters after the decision that peer reviewers were persuaded by what he said as a strong link between plaque reduction and potential clinical benefits. The Aduhelm he said in his briefing was not found in previous studies of drugs designed to eliminate amyloid.

Dr. Stein also said it could be associated beyond the early stages of Alzheimer’s disease and upheld the authorities’ decision to approve the drug for such a wide group of patients.

“Amyloid is a hallmark of the disease throughout its course, so it is hoped that the drug will benefit the entire spectrum,” said Dr. Stein.

As a condition of approval, the FDA required Biogen to conduct another clinical trial, stating that the company would take about nine years to complete it. These terms are also relevant to some professionals. They say the drug is available without restrictions during those years and authorities can revoke approval if the drug is not found to be beneficial in new trials, but with other drugs It’s not mandatory and it’s not always the case.

“There is a problem with the nine-year timeline they provided for so-called confirmatory trials,” said Dr. Kesselheim, who directs the regulatory, treatment, and legal programs at Harvard Medical School. “During that time, the product will be used a lot.”

Three FDA advisors resign from government approval for Alzheimer’s disease treatment

Source link Three FDA advisors resign from government approval for Alzheimer’s disease treatment

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