FDA Grants Full Approval for Donanemab - A New Milestone in Alzheimer's Treatment

Donanemab Overview

The US Food and Drug Administration (FDA) has fully approved Eli Lilly's drug donanemab, branded as KISUNLA, for treating early Alzheimer’s disease, including Mild Cognitive Impairment (MCI) and mild dementia. Donanemab is a monoclonal antibody that targets the beta-amyloid protein, which forms plaques in the brains of people with Alzheimer’s. These plaques disrupt brain cell function. By binding to a specific form of beta-amyloid called N3pG, donanemab helps remove these plaques, slowing the disease's progression.

Clinical Trials

Donanemab's approval came after positive results from Phase 2 and Phase 3 clinical trials. These trials showed that donanemab significantly reduced the amyloid burden in the brain. In the Phase 3 trial, over three-quarters of participants had their amyloid levels lowered to “not elevated” after 18 months. Notably, Eli Lilly stopped treatment for participants once they reached this biomarker response, a strategy now reflected in the FDA-approved label. This label suggests that doctors may stop treatment once amyloid levels reach minimal levels on PET scans.

Efficacy and Approval

The FDA granted full approval not just because donanemab reduces amyloid plaques but also because it slows the clinical progression of the disease compared to a placebo. Donanemab was effective in slowing cognitive decline on both primary and secondary outcome measures, especially in patients at the earliest stages of Alzheimer’s, as identified by tau PET scans.

Approval Details and Accessibility

The FDA label for donanemab requires that patients must have confirmed amyloid presence before starting treatment. There are no specific requirements for tau PET scans, addressing concerns that requiring such scans could limit access, especially in communities with less availability of this imaging technology. The drug is intended for patients with Mild Cognitive Impairment (MCI) or mild dementia.

Comparison with Other Treatments

Donanemab is now one of two approved therapies targeting the biology of Alzheimer’s, alongside lecanemab (developed by Eisai and Biogen). Both drugs share similar safety risks, mainly Amyloid-Related Imaging Abnormalities (ARIA), but they differ in administration. Donanemab requires monthly infusions, while lecanemab requires infusions twice a month. Both treatments require APOE genotype testing before prescription due to higher risks in carriers of the e4 allele of the APOE gene. Comparing their safety and efficacy directly is difficult due to differences in trial populations.

Cost and Market Impact

Donanemab is priced at $32,000 for one year of treatment, compared to $26,500 for lecanemab. While these drugs offer hope, they are not cures. They may slow the progression of cognitive decline but do not stop or reverse it. The long-term effects of stopping treatment after amyloid clearance are still unknown.

Looking Ahead

The approval of donanemab is a significant step forward in Alzheimer’s research, providing new hope for patients with early-stage Alzheimer’s. Ongoing studies aim to see if starting treatment even before memory problems begin can maximize benefits. Despite this progress, there is still a need for better, safer, and more convenient therapies for Alzheimer’s and other forms of dementia.