Cost-Effectiveness of Delaying Alzheimer’s Disease Progression with Novel Monoclonal Antibodies

Abstract

Background: In the US alone, most of over 7.2 million older adults with Alzheimer’s Disease (AD) treat their AD with symptom-relieving therapies. Starting in 2021, three disease-modifying monoclonal antibodies (mAbs) entered the US market as the first disease-modifying treatments for early Alzheimer's disease (AD). Despite years of presence in the US market, the value of these mAbs remains uncertain due to high treatment-related costs and an unclear comparative value of their clinical benefit. Objectives: 1) To estimate the cost-effectiveness of adding aducanumab, lecanemab, or donanemab to the current standard of care (SOC) and 2) to evaluate the value of reducing uncertainties around the mAbs from a US health care perspective and a modified societal perspective. Methods: A Markov simulation model was developed by incorporating literature and a prior cost-impact model of delaying AD progression. The clinical benefit and cohort’s characteristics mirrored results from phase 3 clinical trials of the three agents. The price of the agents was estimated using wholesale acquisition costs published by Micromedex RED BOOK. The model used a 1-week cycle length and estimated 10-year cost impact and comparative incremental cost-effectiveness ratios (ICERs) among the SOC and the mAbs. Results were described from both a health care sector and a societal perspective. One-way sensitivity analysis was conducted to demonstrate key drivers of cost-effectiveness of the mAbs. Cost-effectiveness acceptability curve and the expected value of perfect information (EVPI) used probabilistic sensitivity analysis to demonstrate the comparative value of the mAbs and the value of resolving uncertainties. Results: The three agents were estimated to delay progression from MCI to severe AD by 6.2 - 9.2 months. The analysis showed that SOC costs $243,300 and $757,800 from the health care sector and the modified societal perspective, respectively, over 10 years. From the health care sector perspective, the mAbs incurred additional $55K, $73K, and $82K for aducanumab, lecanemab, and donanemab, respectively. From the modified societal perspectives, donanemab added $73K, and aducanumab and lecanemab added $48K and $64K to the cumulative costs, respectively. Donanemab had the higher comparative ICER at $304,200/QALY, followed by lecanemab at $175,300/QALY. Key driving factors of ICER among lecanemab and donanemab were age at the treatment initiation, patient health state utility values in earlier AD states, and the drug acquisition costs across both perspectives. SOC had more favorable cost-effectiveness at a WTP of $150K/QALY across both perspectives, and lecanemab was more favored at a WTP of $200K/QALY. The EVPI of the decisions around lecanemab versus SOC was estimated to be $143 million at WTP of $190K/QALY and $155K/QALY for the health care sector and the modified societal perspectives, respectively. The EVPI around donanemab versus lecanemab was approximately $109 million at the WTP of $300K/QALY and $275K/QALY for the healthcare sector and the societal perspectives, respectively. Conclusion: In the model simulation, the novel AD treatments incurred substantial costs with modest clinical benefits, with donanemab adding the highest cost. Assuming the treatment costs based on WAC, only lecanemab was found likely to be cost-effective under a WTP of $200K/QALY from the modified societal perspective. The cost-effectiveness of the mAbs is substantially influenced by the patient’s age at the treatment initiation, patient health state utility values at earlier AD states, and the drug acquisition costs.