FDA Approval of Alzheimer’s Drug Causes Advisors to Resign

Alzheimer’s disease is a devastating illness that affects over six million Americans aged 65 years and older. As Alzheimer’s (the most common cause of dementia) progresses, it gradually attacks areas of the brain responsible for communication, reasoning, memory and basic daily tasks. As baby boomers continue to age, the number of people diagnosed with Alzheimer’s is expected to climb.

There are few options available for treatment. None cure Alzheimer’s or treat the underlying damage to the brain. On June 7, the Food and Drug Administration (FDA) approved Aduhelm (aducanumab) as a treatment available to those with Alzheimer’s. This is the first time in more than 17 years that a new treatment has been available for Alzheimer’s disease.

Aduhelm is the first therapy to target the underlying process behind Alzheimer’s. According to the Alzheimer’s Association, plaques and tangles in the brain are suspected of causing damage and killing nerve cells. The tangles are bundles of tau protein that build up inside cells. Plaques are deposits of beta-amyloid, a protein that builds up between nerve cells—both damage these cells, contributing to dementia and other characteristics of Alzheimer’s.

This FDA-approved treatment directly targets the deposits of beta-amyloid using an anti-amyloid antibody intravenous infusion. Experts believe that once Aduhelm sticks to the plaque in brain cells, the immune system will remove it, thinking it is a foreign body. Removing this plaque may slow the progression of this disease, giving hope to those with Alzheimer’s disease and their caregivers. Experts are hopeful that once the plaque is removed, the deterioration of memory and communication behaviors caused by dying brain cells will stop. This is the first treatment of this nature.

Aduhelm treatment is expensive, with the cost estimated to be approximately $56,000 per year. The treatment would require monthly infusions of Aduhelm for the rest of patients’ lives. It is estimated that Biogen set Aduhelm’s list price at $4,312 per infusion.

Accelerated Approval

The FDA granted Aduhelm accelerated approval with a Fast Track designation, stating that this treatment is “intended to provide earlier access to potentially valuable therapies for patients with serious diseases where there is an unmet need, and where there is an expectation of clinical benefit despite some residual uncertainty regarding that benefit.” 

Controversy Surrounding Approval

In November 2020, a team of 11 experts in neurology, Alzheimer’s, and statistics began to review the data presented by U.S.-based Biogen and Japan-based Eisai. After reviewing the clinical trial and the accompanying research data, ten members voted they did not have enough information to approve Aduhelm. The eleventh member was not certain.

Committee members were surprised by the FDA’s decision to approve this treatment. Their concerns highlighted a lack of sufficient evidence to support approval. The committee agreed that Aduhelm did reduce amyloid plaque, but there was no clinical benefit to patients at this time without more study. Biogen and Eisai will be conducting additional clinical studies between now and 2029 to confirm Aduhelm’s treatment benefits to Alzheimer’s patients.

Resignation of Committee Members

After the FDA approved Aduhelm, three members of the committee resigned. Dr. Aaran Kesselheim, professor of medicine at Harvard Medical School; Dr. David Knopman, clinical neurologist at the Mayo Clinic; and Dr. Joel Perlmutter, professor of neurology at Washington University, cited concerns over the FDA’s decision to give Aduhelm the green light as the reason for their resignation.

In an email to Time magazine, Dr. Perlmutter wrote, “As an advisory committee member, I am extraordinarily disappointed that our unbiased advisory committee review was not valued.” 

“It is clear to me that FDA is not presently capable of adequately integrating the Committee’s scientific recommendations into its approval decisions,” said Dr. Kesselheim in an email to StatNews following his resignation. 

The FDA has gone against its advisory committees approximately 20% of the time. When the FDA overrules the advisory committee, votes are normally much closer. The vote with this committee was ten votes against approving Aduhelm and just one being uncertain. The FDA does not have to follow the advisory committee’s recommendations.

Over the years, many research projects have tried and failed to provide treatment options for those with Alzheimer’s, often providing a sense of false hope to caregivers. As more Americans develop Alzheimer’s disease, further research and additional treatments are necessary.