Developments in Donanemab With Brandy Matthews, MD

Brandy Matthews, MD, vice president of medical affairs for neuroscience at Eli Lilly, discussed the mechanism, clinical trial data, and access challenges associated with donanemab (Kisunla) for the treatment of Alzheimer disease.

Matthews explained that donanemab is an IgG1 monoclonal antibody that targets deposited amyloid plaques in the brain, facilitating their removal through microglial-mediated phagocytosis.¹ The agent is indicated for mild cognitive impairment or mild dementia due to Alzheimer's disease in patients with confirmed amyloid pathology. Matthews presented long-term extension data from the TRAILBLAZER-ALZ 2 phase 3 clinical trial, which were featured at the AD/PD 2026 conference in Copenhagen.² The data demonstrated that participants who met treatment completion criteria at 52 weeks achieved robust amyloid lowering, with more than 75% reaching levels below 24.1 centiloids—consistent with a visually negative amyloid PET scan—by 76 weeks. Critically, most participants maintained those reduced levels for up to 3 years following treatment completion.

Matthews noted that posttreatment amyloid reaccumulation occurred at approximately 2.4 centiloids per year, which she described as "consistent with the natural history of amyloid accumulation in older individuals." She emphasized that Kisunla is the only amyloid-targeting therapy with a dosing paradigm that permits treatment discontinuation once plaques are sufficiently reduced, stating that "many patients can complete their donanemab therapy at 76 weeks or even earlier and maintain their amyloid reduction without the need for ongoing treatment."

Despite optimism about the therapeutic pipeline, Matthews expressed concern about persistent systemic barriers to diagnosis and timely specialist referral, particularly in primary care settings. She advocated for expanded access to blood-based Alzheimer biomarker testing as a scalable solution and called for coordinated efforts among industry, academia, policymakers, and governments to bridge the gap between emerging science and clinical practice.

Dr Matthews is the vice president of medical affairs for neuroscience at Eli Lilly.

References

1. Donanemab approved for treatment of early Alzheimer’s disease. Alzheimer’s Association. Accessed April 6, 2026. https://www.alz.org/alzheimers-dementia/treatments/donanemab

2. AD/PD 2026: 3-year data confirms slow amyloid reacumulation following Kisluna treatment completion. Clinical Trials Arena. March 26, 2026. Accessed April 6, 2026. https://www.clinicaltrialsarena.com/analyst-comment/ad-pd-2026-three-year-data-confirms-slow-amyloid-re-accumulation-following-kisunla-treatment-completion/