FDA Approves Donanemab for Early Alzheimer's Treatment Amid Expert Concerns

The FDA has approved Eli Lilly's drug donanemab, branded as Kisunla, for the treatment of early symptomatic Alzheimer's disease. This approval, announced on July 2, follows a positive recommendation from an independent advisory panel, which concluded that the benefits of the drug outweigh its risks.

New Treatment Option

Donanemab, administered as a once-monthly intravenous infusion, is now available for adults with mild cognitive impairment (MCI) and mild dementia who have confirmed amyloid plaques, a hallmark of Alzheimer's disease. Joanne Pike, DrPH, president and CEO of the Alzheimer’s Association, hailed the approval as a significant advancement, stating, "Today’s approval allows people more options and greater opportunity to have more time."

Expert Opinions Diverge

However, expert reactions are mixed. Clifford Segil, DO, a neurologist at Providence Saint John’s Health Center in Santa Monica, CA, expressed serious concerns about the drug's risks. "I believe patients with cerebral edema and brain bleeds will develop vascular dementia in the long run," Segil said, highlighting the potential for serious side effects, including brain swelling and bleeding.

Efficacy and Risks

In trials, donanemab demonstrated the ability to significantly slow cognitive decline in patients with early Alzheimer’s. The drug showed a 35% reduction in cognitive decline for those with low to medium levels of tau protein and a 22% reduction in a broader population. However, these trials also reported amyloid-related imaging abnormalities (ARIAs), which include brain swelling and bleeding.

Monitoring and Safety Measures

Howard Fillit, MD, co-founder and chief science officer of the Alzheimer’s Drug Discovery Foundation (ADDF), emphasized the importance of careful patient selection and monitoring. He noted that patients with certain genetic profiles, particularly those carrying the APOE ε4 gene, are at higher risk for adverse effects. Fillit stated that close monitoring with MRIs is crucial in the early stages of treatment to detect and manage any side effects.

Broader Implications

Donanemab is one of three monoclonal antibody treatments approved for Alzheimer’s, joining aducanumab (Aduhelm) and lecanemab (Leqembi). These drugs target amyloid plaques, but their ability to significantly improve cognitive function remains debated. The approval of donanemab is seen as a step toward more personalized and effective treatments for Alzheimer’s, but the journey is far from over.

Fillit described donanemab as a building block for future generations of Alzheimer's treatments, underscoring the need for continued development of therapies targeting the underlying biology of the disease. "Anti-amyloids are not a silver bullet, but they offer opportunities for patients to modify the course of the disease," he said.

The FDA’s approval of donanemab marks a critical milestone in Alzheimer’s treatment, providing a new option for patients and their families. However, the medical community remains cautious, emphasizing the need for ongoing surveillance and research to ensure the safety and efficacy of this and similar treatments