New Alzheimer’s Drug Donanemab that Slows Symptoms Progression Gains Support from FDA Advisers

On the 10th of June 2024, a significant development in the medical field emerged as independent scientists advising the US Food and Drug Administration (FDA) unanimously approved a drug for Alzheimer’s disease. This decision marks a crucial step towards introducing the drug, known as donanemab, for clinical use. Produced by Eli Lilly, based in Indianapolis, Indiana, donanemab is poised to become the second drug in the US market designed to slow down the cognitive decline associated with Alzheimer’s disease.

During a meeting at the FDA’s headquarters in Silver Spring, Maryland, all 11 members of an FDA independent scientific advisory committee voted in favour of donanemab’s efficacy in treating Alzheimer’s, particularly in individuals in the early stages of the disease. The committee also concluded that the benefits of the drug outweigh its risks, although some questions remain regarding the durability of its effects and certain limitations on its usage that the FDA may impose.

Donanemab functions as an antibody that targets amyloid, a protein that tends to accumulate in the brains of individuals with Alzheimer’s. Clinical data submitted to the FDA by Eli Lilly revealed that participants in the trial who received donanemab exhibited a slower decline in cognitive abilities compared to those who received a placebo. However, it is essential to note that donanemab does not reverse the progression of the disease itself. Studies indicate that donanemab performs similarly to another drug, lecanemab, which also targets amyloid and is developed by Eisai and Biogen.

Unlike previous trials involving monoclonal antibodies, Eli Lilly’s study specifically focused on individuals whose brains contained both amyloid and another protein called tau, which is linked to cognitive decline. Interestingly, donanemab appeared to be more effective in individuals with lower to moderate levels of tau at the beginning of the trial than in those with higher levels. However, it was noted that disease progression might have been slower in individuals with lower tau levels, potentially impacting the interpretation of the results.

During the advisory committee meeting, concerns were raised regarding the lack of evidence demonstrating donanemab’s efficacy in individuals with minimal to no tau present. Despite this concern, the committee decided against restricting the drug’s use based on tau levels due to the complexity and cost associated with screening for tau. Implementing such a requirement could prevent a significant number of individuals from accessing the drug, prompting the committee to favour broader access.

Another point of contention highlighted during the meeting was the occurrence of amyloid-related imaging abnormalities (ARIA), which are associated with potentially severe consequences such as brain bleeding and seizures. Eli Lilly reported more instances of ARIA-related deaths among those who received donanemab compared to the placebo group. This is a notable concern given that ARIA has also been linked to lecanemab, albeit with a higher risk observed with donanemab.

The approval of donanemab represents a positive development for drugs targeting amyloid in Alzheimer’s disease treatment, following several controversies surrounding similar medications. In 2021, despite objections from its advisory committee, the FDA approved aducanumab, another drug produced by Biogen and Eisai. This decision led to resignations from committee members and raised doubts among insurers regarding the drug’s efficacy, resulting in limited coverage. Biogen ceased production of aducanumab earlier this year due to these challenges.

Experts emphasise that further research is necessary to fully understand donanemab’s potential, including its optimal duration of administration and efficacy in individuals with varying levels of tau. It remains uncertain whether the modest effects of the drug will endure over an extended period. Additionally, there is a call for more research on donanemab’s effectiveness in diverse populations, as a significant majority of participants in Eli Lilly’s trials were white. Furthermore, data on the drug’s impact on individuals with Down’s syndrome or genetic predispositions to Alzheimer’s and ARIA are deemed essential for broader applicability.

While the approval of donanemab signifies progress in Alzheimer’s disease treatment, ongoing research and vigilance are paramount to fully comprehend its impact and ensure safe and effective usage across diverse populations. The FDA’s final decision on donanemab is anticipated later this year.

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