ADDF Statement on FDA Approval of Donanemab (Kisunla)

The approval of the monoclonal antibody donanemab (Kisunla) by the FDA marks a significant milestone in the treatment of mild cognitive impairment and early-stage Alzheimer's disease. This approval is particularly notable because it is the first anti-amyloid therapy with evidence to support stopping treatment once amyloid plaques are removed from the brain. This breakthrough, paired with advances in the biology of aging, brings the medical community closer to treating Alzheimer's disease through a combination of therapies and precision medicine approaches similar to those used in cancer care.

According to Howard Fillit, MD, Co-Founder and Chief Science Officer at the Alzheimer's Drug Discovery Foundation (ADDF), this approval symbolizes a new era in Alzheimer's research. The emergence of disease-modifying drugs that can be used in combination with novel therapies targeting the complexities of Alzheimer's is a promising development. Dr. Fillit highlights that some patients have achieved full amyloid clearance and have not experienced substantial plaque buildup for several years, essentially entering remission.

Anti-amyloid drugs have shown effectiveness in slowing cognitive decline by about 30%, which underscores the need for developing additional therapies targeting the underlying biology of Alzheimer's disease. The current drug development pipeline is robust, with nearly 75% of drugs focusing on targets beyond amyloid and tau proteins. With two approved drugs now on the market and more in development, the field is poised to adopt a combination therapy approach, starting with early and accurate diagnosis.

Dr. Fillit notes that the focus has shifted from merely diagnosing Alzheimer's to detecting it as early as possible. The validation of new biomarkers, including blood tests, is making it easier to diagnose the disease and intervene earlier, even in the preclinical phase. These advances open the door to preventative measures, allowing for the administration of the right drugs to the right patients at the right time.

The role of biomarkers in facilitating drug development is highlighted by the Kisunla study, where Eli Lilly & Company utilized the Amyvid® PET scan and the C2N blood test, PrecivityAD®. Both of these biomarkers received early seed-funding from the ADDF, aiding in trial enrollment and monitoring drug target engagement. The trial demonstrated the value of simultaneous drug and biomarker development, leading to more efficient and rigorous clinical trials. With new biomarkers, physicians can better understand patients' individual risk profiles, enabling earlier diagnosis and the combination of therapeutics with lifestyle interventions to slow disease progression.

While the approval of Kisunla is a significant advancement, Dr. Fillit emphasizes the importance of continuing to develop new therapies and biomarkers based on the biology of aging. The goal is to halt the progression of Alzheimer's or prevent it entirely. In the next five years, the combination of lifestyle interventions and therapeutics tailored to individual patient needs is expected to further slow cognitive decline.

The Alzheimer's Drug Discovery Foundation, founded in 1998, remains dedicated to accelerating the discovery of drugs to prevent, treat, and cure Alzheimer's disease. The foundation has played a pivotal role in bringing critical diagnostic tools like the Alzheimer's PET scan (Amyvid®) and the blood test (PrecivityAD®) to market. Through the support of its donors, the ADDF has awarded over $290 million to fund more than 750 Alzheimer's drug discovery programs, biomarker initiatives, and clinical trials across 20 countries.