A recent investigation has brought to light concerns regarding the conduct of clinical trials for Leqembi, an Alzheimer's disease drug developed by Eisai. The investigation alleges that Eisai did not fully disclose genetic risk information to trial participants, potentially exposing them to increased risks of brain bleeds and swelling. This revelation raises ethical questions about informed consent and patient safety in pharmaceutical research.
Alleged Lack of Genetic Risk Disclosure
The New York Times investigation revealed that Eisai recruited volunteers for Leqembi clinical trials and conducted genetic testing to identify those with a predisposition to Alzheimer's disease. The company reportedly indicated that the same gene could also increase the risk of brain bleeds or swelling if the volunteers took the drug. However, it's alleged that Eisai did not disclose the results of these genetic tests to the participants, a practice that ethicists deem a violation of informed consent rules.
According to the report, this lack of disclosure was not previously reported during drug trial reviews or when the FDA approved the drug for the U.S. market. The information only surfaced after journalists reviewed clinical trial data, patient records, injury reports, and conducted interviews with researchers, neurologists, trial participants, families, and FDA officials.
Adverse Events and Limited Efficacy
The investigation suggests that more than 100 volunteers who did not receive their genetic test results experienced brain bleeding and swelling. Some suffered severe and life-threatening symptoms, and several deaths were reported. One participant reportedly died after experiencing 51 brain bleeds after only three doses of the drug; an autopsy linked the death directly to Leqembi's side effects.
Furthermore, the data from the drug trials indicated that Leqembi's benefits were modest. Patients experienced a slowing of cognitive decline by a few months, but the drug did not prevent complete cognitive decline. This has led some researchers to question the dominant theory that Alzheimer's is primarily caused by plaque in the brain.
Regulatory Scrutiny and Approval
Despite these concerns, the FDA granted accelerated approval to Leqembi in 2023, determining that the benefits outweighed the risks. However, this decision has faced criticism, particularly in light of the alleged lack of transparency in the clinical trials.
Notably, European Union drug regulators recommended against approving Leqembi in July, and Australia also declined to approve the drug earlier this month. Both cited that the temporary delay of cognitive decline (at most five months) did not outweigh the risks of Leqembi's side effects.
Broader Concerns About FDA Bias
The FDA's approval of Leqembi has reignited discussions about potential bias toward approving new drugs, particularly in the context of Alzheimer's treatments. The agency faced criticism after approving Aduhelm in 2021, despite an advisory committee voting against its approval and raising concerns about the lack of evidence of patient benefit. This approval led to resignations from the advisory committee and a Congressional report highlighting a close relationship between the FDA and the drug's manufacturer, Biogen.
