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Contributed by Joshua Grill, PhD and Jason Karlawish, MD

UCI MIND Director Joshua Grill, PhD co-authored an article in Nature Reviews Neurology about the FDA’s decision on Aduhelm. Read more on this below:

Since the FDA approved Aduhelm (aducanumab) on June 7, there has been considerable conversation, debate, and even backlash about the decision. It may seem difficult to keep up. Here is a recap of some of the most recent important events.

The FDA granted Aduhelm what is known as “accelerated approval.” This means that the approval did not indicate that the drug has been adequately shown to benefit patients, but instead that Aduhelm had been shown convincingly to lower brain amyloid levels. Amyloid is the abnormal protein that accumulates in the brain of a person with Alzheimer’s disease. The FDA deemed it “reasonably likely” that lowering brain amyloid would produce a clinical benefit. Approval based on amyloid as a “surrogate outcome” came as a shock to many in the field, since before this decision amyloid was not deemed a validated surrogate and other drugs had effects on amyloid without producing clinical benefit. Since the decision, Eli Lilly has requested accelerated approval for their amyloid-lowering drug, donanemab, and other companies may follow suit.

Another controversial aspect of the decision was that the drug was approved for “Alzheimer’s disease” and no further restrictions based on disease severity were included in the prescribing information. The FDA and Biogen amended this last week, now including in the prescribing information for Aduhelm that it is intended for patients with Mild Cognitive Impairment or mild dementia—the types of patients that were included in the clinical trials of the drug. This important change doesn’t preclude a physician from prescribing Aduhelm for other patients, but there are no data on the safety or efficacy of Aduhelm in patients with more severe disease to guide clinicians. Still absent from the indication is the requirement to confirm that patients have elevated brain amyloid, which can be done through PET imaging or cerebrospinal fluid analysis. There is no reason to expect patients who don’t have elevated amyloid would benefit from Aduhelm therapy and since patients without elevated brain amyloid were excluded from clinical trials, safety data are also lacking for these patients.

The FDA’s role in Aduhelm’s approval is also being scrutinized. Last week UCI law professor and US Rep. Katie Porter called for investigation of the approval process and multiple congressional hearings are now planned. These hearings will focus both on the approval process and the announced price of the drug, which is $56,000/year once the presumed efficacious dose of the monthly infused medication has been reached. Unfortunately, this price tag does not include the other anticipated costs of using aducanumab, which some colleagues estimate will reach $100,000 per year. It is still not clear how much of this cost families will bear. A key event yet to happen will be coverage decisions by the Centers for Medicare and Medicaid Services and private insurers, a process that began on July 12.

These unfolding events and the headlines they’ve drawn have been frequent and emotionally fraught. The main achievements of developing potentially efficacious treatments for Alzheimer’s disease should have been a celebrated milestone. Yet, the inexplicable decisions by regulators have cast shadows on scientific successes. Scientists, public health officials, and regulators will need to work hard to overcome challenges and regain public trust. Only when all stakeholders are aligned and working closely together in harmony will we most efficiently discover solutions for this devastating disease.


Joshua Grill, PhD, is an Associate Professor of Psychiatry & Human Behavior and Neurobiology & Behavior at UCI. He serves as Director of UCI MIND, Associate Director of the UCI Alzheimer’s Disease Research Center, and Leader of the Recruitment & Retention Unit for the UCI Institute for Clinical and Translational Science. His research focuses on clinical trials across the spectrum of Alzheimer’s disease, and he has published a number of important findings on trial design, recruitment and retention, and research ethics.