Editor’s note: Schaeffer Scholar Jack Chapel presented this abstract at the Clinical Trials on Alzheimer’s Disease (CTAD) conference on Dec. 2, 2025. These results are preliminary and have not yet undergone peer review. Slides from the CTAD presentation are available here.
Abstract
Background: Novel anti-amyloid therapies for Alzheimer’s disease (AD) can slow disease progression.1,2 Emerging blood-based biomarker tests are expanding screening and diagnostic options, which could facilitate timely treatment initiation. Research investigating the potential complementary value of these innovations is needed to inform monitoring and treatment strategies that will maximize societal benefit while containing costs. This study quantifies the long-term societal value of anti-amyloid therapy and the potential gains in value that could be achieved from earlier treatment initiation, consistent with improving monitoring of biomarkers and cognition.
Methods: We used the Future Elderly Model (FEM)—an established and well-validated dynamic microsimulation—to estimate the long-term health and economic impacts of donanemab treatment among participants of TRAILBLAZER-ALZ 2, the pivotal phase 3 trial of donanemab.1 FEM is based on nationally representative data including the Health and Retirement Study (HRS). We estimated models of Clinical Dementia Rating–Sum of Boxes (CDR-SB) progression using data from the Alzheimer’s Disease Neuroimaging Initiative (ADNI). To construct the simulation cohort, we used ADNI data to estimate the clinical trial participants’ CDR-SB two years before trial entry, and then used HRS to create a simulant population matching the trial participants’ baseline characteristics and estimated recent trajectory of CDR-SB. Treatment was modeled as a 29% slowing of CDR-SB progression, consistent with TRAILBLAZER-ALZ 2. We simulated individuals’ remaining life without treatment (Status Quo) and counterfactual treatment scenarios: (i) Baseline Treatment initiated treatment at the clinical trial baseline (mean age 73); (ii) Earlier Treatment initiated treatment two years before trial baseline (mean age 71); (iii) additional scenarios explored initiating treatment starting as early as the presymptomatic stage (mean age 68). We quantified the total value of treatment for individuals’ remaining life compared to Status Quo, including impacts on the quality of life of the persons living with AD and their care partners, medical costs, caregiving costs, and earnings. Total value was calculated as the present value at treatment initiation using a 3% discount rate and reported in 2025 USD. In sensitivity analyses, we varied the magnitude of the treatment effect (rate of slowing) and the persistence of the treatment effect.
Results: The simulated trajectory of CDR-SB closely aligned with the trajectory observed in the clinical trial placebo group. Total lifetime value of donanemab in the Baseline Treatment scenario relative to Status Quo was $113,000 per treated individual. Total lifetime value in the Earlier Treatment scenario was $151,000, representing a 34% increase in value resulting from two-year earlier treatment initiation. Gains in patient quality of life were the largest source of value (55%-56%), followed by reductions in caregiving costs (20%), reductions in medical costs (17%-18%), gains in quality of life of care partners (5%), and higher lifetime earnings (1%). Reductions in medical costs were driven by 12%-16% reductions in annualized Medicaid spending, stemming from significantly lower nursing home use with 0.7 and 0.9 more years spent living in the community in the Baseline and Earlier Treatment scenarios, respectively. In analyses varying the treatment effect magnitude (rate of slowing) and persistence, the gains that resulted from innovations improving these two parameters were compounded when combined with earlier treatment. In additional analyses, scenarios initiating treatment at symptom onset and presymptomatic stages resulted in nearly triple the total value compared to Baseline Treatment, depending on treatment effect assumptions.
Conclusion: With current anti-amyloid therapies and screening technology, we estimate there is substantial societal value to be gained from improving monitoring and treatment initiation timing. Back of the envelope calculations suggest that, for the 12.7 million Americans projected to be living with AD in 2050,3 donanemab-like treatment could generate up to $1.4 trillion in total lifetime value if administered as in the clinical trial and $1.9 trillion if initiated just two years earlier; the availability of earlier treatments targeting the presymptomatic stage could further increase value up to $3.9 trillion.
Keywords: health economics, societal value, microsimulation, anti-amyloid therapy
Disclosures: The USC Schaeffer Center for Health Policy & Economics received funding from Lilly; the authors retained full control of research design, analyses, and conclusions. Dr. Chapel is supported by the USC Schaeffer Center—which receives funding from foundations, government agencies, individuals, and corporations, including Lilly—and grants from NIH. Dr. Aisen has research grants from NIH, the Alzheimer’s Association, Lilly and Eisai, and consults with Merck, Roche, Genentech, Abbvie, Biogen, ImmunoBrain Checkpoint, AltPep, Bristol Myers Squibb, Johnson&Johnson, New Amsterdam and Neurimmune. In the last three years, Dr. Goldman reports grants from American Heart Association, Alexion, Amgen, Biomarin, Blue Cross Blue Shield of Arizona, Blue Cross Blue Shield of Massachusetts, BrightFocus, Bristol Myers Squibb, California Hospital Association, Cedars-Sinai Health System, Charles Koch Foundation, CommonSpirit, Edwards Lifesciences, Gates Ventures, Genentech, Gilead Sciences, Incyte, Johnson & Johnson, Lilly, National Institute on Aging, National Institute of Diabetes and Digestive and Kidney Diseases, Novartis, Pfizer, RA Capital, and Roche; personal fees from Edwards Lifesciences, and GRAIL. He is a co-founder of EntityRisk and holds equity in the company.
References:
- Sims JR, Zimmer JA, Evans CD, et al. Donanemab in Early Symptomatic Alzheimer Disease: The TRAILBLAZER-ALZ 2 Randomized Clinical Trial. JAMA. 2023;330(6):512. doi:10.1001/jama.2023.13239
- Dyck CH van, Swanson CJ, Aisen P, et al. Lecanemab in Early Alzheimer’s Disease. N Engl J Med. 2023;388(1):9-21. doi:10.1056/NEJMoa2212948
- Alzheimer’s Association. 2025 Alzheimer’s Disease Facts and Figures. Alzheimers Dement. 2025;21(5).
Key takeaway message: Earlier initiation of anti-amyloid therapy, consistent with improved monitoring of cognition and biomarkers, could substantially increase the long-term societal value of treatment.
