3 FDA advisers resign over agency’s approval of Alzheimer’s drug

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Written by Pam Belluck and Rebecca Robbins

In a strong assertion of disagreement with the Food and Drug Administration’s approval of Biogen’s controversial Alzheimer’s drug this week, three scientists have resigned from the unbiased committee that suggested the company on the therapy.

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“This might be the worst approval decision that the FDA has made that I can remember,” mentioned Dr. Aaron Kesselheim, a professor of drugs at Harvard Medical School and Brigham and Women’s Hospital, who submitted his resignation Thursday after six years on the committee.

He mentioned the agency’s approval of the drug, aducanumab, which is being marketed as Aduhelm, a month-to-month intravenous infusion that Biogen has priced at $56,000 per yr, was unsuitable “because of so many different factors, starting from the fact that there’s no good evidence that the drug works.”

Two different members of the committee resigned earlier this week, expressing dismay on the approval of the drug regardless of the committee’s overwhelming rejection of it after reviewing medical trial information in November.

The committee had discovered that the proof didn’t convincingly present that Aduhelm may gradual cognitive decline in folks within the early levels of the illness — and that the drug may trigger probably critical unwanted effects of mind swelling and mind bleeding. None of the 11 members of the committee thought of the drug prepared for approval: Ten voted towards, and one was unsure.

“Approval of a drug that is not effective has serious potential to impair future research into new treatments that may be effective,” mentioned Dr. Joel Perlmutter, a neurologist at Washington University School of Medicine in St. Louis, who was the primary to resign from the committee.

“In addition, the implementation of aducanumab therapy will potentially cost billions of dollars, and these dollars may be better spent in either developing better evidence for aducanumab or other therapeutic interventions,” Perlmutter added.

Shannon P. Hatch, a spokesperson for the FDA, mentioned the company doesn’t touch upon issues associated to particular person members of advisory committees.

Biogen plans to start delivery out the drug in about two weeks. It expects greater than 900 websites throughout the nation, sometimes reminiscence clinics that see sufferers with dementia, to quickly be able to administer the drug.

The FDA’s resolution to green-light Aduhelm marked the primary approval of an Alzheimer’s therapy in 18 years. Patient advocacy teams had pushed for approval as a result of there are solely 5 different drugs out there for the debilitating situation they usually solely handle dementia signs for a matter of months.

But since a minimum of final fall, a number of revered specialists, together with some Alzheimer’s medical doctors who labored on the aducanumab medical trials, have mentioned the out there proof raised vital doubts about whether or not the drug is efficient. They additionally mentioned that even when it may gradual cognitive decline in some sufferers, the recommended profit — a slowing of signs for roughly 4 months over 18 months — could be barely noticeable to sufferers and wouldn’t outweigh the dangers of mind unwanted effects.

Beyond the steep price ticket of the drug, extra prices to display sufferers earlier than therapy and for normal MRIs required to watch their brains for issues may add tens of hundreds of {dollars} to the tab. Medicare is predicted to shoulder a lot of the invoice.

“Giving patients a drug that doesn’t work and of course has important risks that are going to require multiple MRIs at a price of $56,000 a year is putting patients in a really challenging position and putting doctors in a difficult position as well,” Kesselheim mentioned.

Beyond their conviction that the prevailing proof for Aduhelm’s profit is weak, the advisory committee members who resigned — in addition to a number of outstanding Alzheimer’s specialists — objected to 2 main elements of the FDA’s approval resolution.

One challenge is that the FDA permitted the drug for a much wider group of sufferers — anybody with Alzheimer’s — than many specialists had been anticipating. The medical trials examined the drug solely on sufferers with early-stage Alzheimer’s or gentle cognitive impairment from the illness.

The different challenge is {that a} vital half of the FDA’s rationale for granting approval was its competition that the drug’s potential to assault the amyloid protein in sufferers’ brains would assist gradual their cognitive signs.

“This is a major problem,” Perlmutter mentioned.

While amyloid is taken into account a biomarker of Alzheimer’s illness as a result of its accumulation within the mind is a key side of the situation, there was little or no scientific proof that decreasing amyloid can really assist sufferers by easing their reminiscence and pondering issues.

In November, FDA officers instructed the advisory committee members that the company wouldn’t be counting the drug’s potential to cut back amyloid as a sign that it could be efficient. But in Monday’s resolution, the FDA introduced that it had performed simply that.

(*3*) the FDA’s director of the Center for Drug Evaluation and Research, Dr. Patrizia Cavazzoni, wrote on the agency’s web site concerning the resolution to make the drug out there below a program referred to as accelerated approval.

But advisory committee members mentioned the committee was by no means instructed that the company was planning to contemplate approval primarily based on amyloid discount and that their opinion was by no means sought about that vital change. Perlmutter mentioned the committee was “not made aware of any additional information or statistical analyses that would support” approval.

Dr. David Knopman, a medical neurologist on the Mayo Clinic, wrote in an e-mail to FDA officers informing them of his resignation from the advisory committee on Wednesday: “Biomarker justification for approval in the absence of consistent clinical benefit after 18 months of treatment is indefensible.”

Dr. Peter Stein, who directs the FDA Center for Drug Evaluation and Research’s Office of New Drugs, mentioned in a briefing with reporters after the choice that company reviewers had been persuaded by what he described as a powerful relationship between plaque discount and potential medical profit with Aduhelm, which he mentioned had not been seen in earlier research of medication designed to clear amyloid.

This article initially appeared in The New York Times.

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