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Aduhelm® Alzheimer’s Disease Drug: The FDA Approval Backlash

By Rheingold Giuffra Ruffo & Plotkin LLP

A recently approved Biogen Alzheimer’s drug, Aduhelm® (Aducanumab), raises questions about the ethics of a laissez-faire, profit-driven medical industry. Despite the Food & Drug Administration’s accelerated approval, Aduhelm® has been unable to demonstrate major benefits and has instead proven to cause significant health risks to patients with Alzheimer’s disease.

What is Aduhelm®?

Biogen has described Aduhelm® as an immunoglobulin monoclonal antibody that can supposedly lower amyloid beta plaques in the brain for patients with mild Alzheimer’s disease.

An increase of amyloid beta plaques are a fundamental pathophysiological characteristic of Alzheimer’s disease—a condition that causes dementia, which leads to a progressive onset of cognitive decline. It is incredibly life-changing, challenging, and stressful for the people caring for and people living with Alzheimer’s.

Industry-sponsored clinical research for drugs to prevent or slow the onset of Alzheimer’s was not prominent until the 2010s. In fact, the first major clinical trial for Alzheimer’s disease prevention did not begin until 2012. Up until the approval of Aduhelm®, there had only been failed clinical trials for experimental therapies. The last treatment that received FDA approval was in 2003, but it was not a targeted treatment like Aduhelm®.

It is understandable that as a family member, carer, and/or care professional of a person with Alzheimer’s, it is frustrating to not have answers when you ask if there’s any treatment for the condition. Many have become so determined to help find a treatment for an Alzheimer’s patient that they would pay $56,000—the annual price of Aduhelm®.

Why is the Approval of Aduhelm® Facing Backlash?

After a 2019 vote by the FDA advisory committee of insufficient evidence to support the drug’s efficacy, it seemed that Aducanumab’s approval would take a much longer time. However on June 7, 2021, the drug met “accelerated approval” requirements under regulatory standard 21 CFR 601.41 and was subsequently approved by the FDA.

According to the FDA’s website, the Accelerated Approval Program “allow[s] for earlier approval of drugs that treat serious conditions, and that fill an unmet medical need” based on a predicted clinical benefit. Biogen must conduct a Phase 4 confirmatory trial to prove the drug’s benefits, and the drug will remain on the market in the meantime for qualified patients with mild Alzheimer’s disease.

The problem with Aduhelm® receiving accelerated approval is that it had not yet proven significant clinical benefits in its earlier trials. Its first study concluded that “differences from placebo observed in the ADUHELM low dose group numerically favored ADUHELM but were not statistically significant.” Its second study concluded that “No statistically significant differences were observed between the ADUHELM-treated and placebo-treated patients on the primary efficacy endpoint.”

In fact, the drug was proven to significantly increase the incidence of adverse effects, such as cerebral edema, cerebral microhemorrhages, headache, and mental disorientation.

What Role Does the FDA Play?

The concern of unethical practices within the FDA continues to erode scientific and public confidence in Aduhelm®. The health site STAT reported that the relationship between Biogen and the FDA has stretched far beyond what is considered ethical.

As discussed in Science in the Public Interest by Sheldon Krimsky, federal conflict of interest laws prohibit government officials from personally capitalizing on their work. However, on advisory boards in which scientific experts evaluate biomedical goods that require approval from the government, agencies can “choose to exercise the waiver provision of the U.S. statutes [on conflict of interest].” A waiver can be issued by appointing officers of the FDA.

Furthermore, Krimsky uncovered that among 50% of 159 FDA advisory meetings, at least half of the committee had financial stakes (stock ownership, consulting fees, research grants) in the topic under review. This caused controversies for the FDA, so the agency chose to stop disclosing committee members’ conflicts of interest altogether.

The Ethics in Government Act does not require agencies to publicly disclose an advisory committee member’s main place of employment, contractual relationships, or relevant investments. In fact, ethical standard enforcement is so loose that even when committee members are disqualified from voting on recommendations, they are still permitted to participate in the discussions leading up to a vote.

Since the approval of Aduhelm®, the FDA’s acting commissioner has called for an independent investigation of off-the-record meetings between the federal agency and Biogen that led to the approval of the Alzheimer’s disease drug. Additionally, two members of the advisory panel have since resigned to protest the approval of Aduhelm®.

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