In the ongoing battle against Alzheimer's disease, a glimmer of hope emerged yesterday with the Food & Drug Administration’s (FDA) unanimous approval of experimental drug, donanemab, bringing the treatment closer to use in the clinic.
During a meeting on June 10th at the FDA’s headquarters in Silver Spring, Maryland, all 11 members of an independent scientific advisory committee voted to affirm that donanemab, produced by Eli Lilly headquartered in Indianapolis, Indiana, is effective in treating Alzheimer's, particularly in individuals in the early stages of the disease, and that its benefits justify its risks. The phase 3 trial results in testing donanemab showed a slowed clinical decline by 35% in participants within early stages of the disease compared to the placebo and resulted in 40% less decline on the ability to perform activities of daily living. This resounding endorsement underscores the potential of targeted therapies, such as donanemab, to address the complexities of Alzheimer's pathology and offers hope for improved outcomes for patients and their families.
Implications and Controversies
During the meeting, advisory committee members largely expressed support for the drug. However, some pointed out that Lilly has limited evidence of its efficacy in individuals with minimal to no tau presence. Despite this, the committee opted against imposing restrictions on the drug's usage based on tau levels due to the complexity and expense of tau screening. Implementing such a requirement would disproportionately limit access to the drug. Additionally, panel members raised concerns about amyloid-related imaging abnormalities (ARIA), a condition associated with brain bleeding and seizures. ARIA, which can be fatal, is believed to occur when antibodies weaken blood vessels in the brain. Lilly documented a higher number of ARIA-related deaths among those who received the drug compared to the placebo group. Expanded research on the drug's efficacy across diverse demographic groups, particularly people of color is also necessary—given that more than 90% of Lilly's trial participants were white—and individuals with Down syndrome or genetic predispositions to amyloid-related imaging abnormalities (ARIA). While lecanemab, the only FDA approved Alzheimer’s treatment available today that has also been associated with ARIA, the risk appears to be significantly greater with donanemab.The donanemab committee emphasized the necessity for further research on the drug, encompassing inquiries into its optimal duration of administration and its effectiveness in individuals with varying levels of tau. There are doubts regarding whether the decrease in amyloid plaques witnessed with this drug will result in significant clinical benefits.
Drug Mechanisms
Donanemab is a drug administered through IV that operates through a mechanism aimed at clearing amyloid plaques, a characteristic feature of Alzheimer's disease pathology. These plaques are composed of abnormal clusters of beta-amyloid protein that accumulate in the brain, disrupting neural function and contributing to cognitive decline. Donanemab targets a specific form of beta-amyloid known as N3pG, which is believed to play a crucial role in the formation and persistence of amyloid plaques. By binding to and facilitating the removal of N3pG-beta-amyloid, donanemab promotes the clearance of amyloid plaques from the brain, slowing the progression of Alzheimer's disease by addressing one of its underlying causes.
The Road Ahead
The FDA’s final decision on donanemab is expect later this year; however, their current endorsement represents a significant step forward in Alzheimer's treatment. Eli Lilly and Company will need to conduct further studies to confirm the drug's safety and efficacy, as well as navigate the regulatory approval process for full market authorization before the drug can be widely prescribed. Additionally, questions remain about the cost and accessibility of donanemab, particularly given the prevalence of Alzheimer's and the potential for high demand for the drug.
Beyond donanemab, the FDA's decision underscores the need for continued investment in Alzheimer's disease research and the development of innovative treatments for all forms of dementia. If donanemab receives full FDA approval in the future, it will be one of only two available treatment options for slowing the decline in Alzheimer’s disease alone, not applicable to the 100 other forms of dementia. Dementia remains one of the most pressing public health challenges of our time, with profound social, economic, and personal implications. Finding effective therapies to prevent, slow, or even reverse the progression of all disease forms is imperative to improve the lives of millions of individuals and their families.
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