FDA Approves Controversial Alzheimer Disease Drug

In June 2021, the U.S. Food and Drug Administration (FDA) approved aducanumab (Aduhelm), a drug intended to slow the progression of Alzheimer disease. The drug is designed to reduce amyloid beta plaques in the brain. While the exact cause of Alzheimer disease is not known, buildup of these plaques is a distinctive feature of the disease. The plaques play a role in damaging nerve cells and causing other unwanted changes in the brain.

Aducanumab is the first treatment for Alzheimer disease approved by the FDA since 2003.

The FDA used the accelerated approval pathway to approve the drug. The FDA employs this accelerated pathway when a treatment for a serious or life-threatening illness can offer a significant advantage over current treatments. Currently available therapies only treat the symptoms of Alzheimer disease. Aducanumab is the first approved treatment for slowing down the progression of the disease.

Alzheimer disease is an irreversible disease that affects 6.2 million Americans, most commonly adults aged 60 and older. The disease is characterized by memory loss, cognitive decline, changes in personality, and an inability to independently perform simple tasks.

CEO and president of the Alzheimer’s Association Harry Johns describes the FDA’s approval of aducanumab as a victory for patients with Alzheimer disease and their families. The organization’s chief medical officer, Maria C. Carillo, anticipates the historic approval will welcome a new era of innovation in drug treatments for Alzheimer disease.

Although the aducanumab treatment seems promising, the FDA’s decision comes with controversy. In two phase III clinical trials of the drug, researchers found opposite results. One trial showed the drug was effective at slowing the progression of Alzheimer disease. The other trial concluded the drug was not effective.

Both trials were paused in March 2019 by the drug’s maker, Biogen, after analyses indicated the drug was unlikely to succeed. Additional analyses conducted by Biogen after the trials stopped led the company to conclude that there was sufficient evidence the drug was successful.

Back in November 2020, an advisory panel to the FDA voted that the data was too inconsistent to approve aducanumab for treatment of Alzheimer disease and did not show that the drug slowed Alzheimer disease. The FDA’s recent approval of the drug dismisses these concerns. In a statement, Dr. Patrizia Cavazzoni, Director of the FDA Center for Drug Evaluation and Research said that “the Agency concluded that the benefits of Aduhelm for patients with Alzheimer disease outweighed the risks of the therapy.”

As a condition for accelerated approval, the FDA is requiring Biogen to conduct a new clinical trial to verify the benefits of the drug, and to demonstrate that a reduction in plaques slows progression of the disease. If Biogen’s new trial fails to verify the drug’s benefits, the FDA can initiate a process for withdrawing its approval of the drug.

Critics of the FDA’s approval express concern that Biogen will not find enough participants for the new trial. Participation in a trial comes with a risk of being given a placebo, rather than aducanumab. Those who want the drug can purchase it without being part of the study.

The annual cost of aducanumab would be $56,000 for patients in the United States of average weight and who have mild dementia or mild cognitive impairment. The drug is administered to patients via monthly infusions. Patients who receive the drug will also need regular MRI brain scans to detect swelling or bleeding in the brain, which are rare side effects.

Given the mixed research results, cost, and side effects, some healthcare providers may be reluctant to recommend the new drug to their patients. Further data from additional trials will provide greater insight into the efficacy of aducanumab.