Introduction: Aducanumab was granted accelerated approval with a conflicting evidence base, near-unanimous FDA Advisory Committee vote to reject approval, and a widely criticized launch price of $56,000 per year. The objective of this analysis was to estimate its cost-effectiveness.

Methods: We developed a Markov model to compare aducanumab in addition to supportive care to supportive care alone over a lifetime horizon. Results were presented from both the health system and modified societal perspective. The model tracked the severity of disease and the care setting. Incremental cost-effectiveness ratios were calculated, and a threshold analysis was conducted to estimate at what price aducanumab would meet commonly used cost-effectiveness thresholds.

Results: Using estimates of effectiveness based on pooling of data from both pivotal trials, patients treated with aducanumab spent four more months in earlier stages of AD. Over the lifetime time horizon, treating a patient with aducanumab results in 0.154 more QALYs gained per patient and 0.201 evLYGs per patient from the health care system perspective, with additional costs of approximately $204,000 per patient. The incremental outcomes were similar for the modified societal perspective. At the list price of $56,000 per year, the cost-effectiveness ranged from $1.02 million per evLYG to $1.33 million per QALY gained from the health care system perspective; and from $938,000 per evLYG to $1.27 million per QALY gained in the modified societal perspective. The annual price to meet commonly used cost-effectiveness thresholds ranged from $2,950 to $8,360, which represents a discount of 85-95% off from the annual launch price set by the manufacturer. Using estimates of effectiveness based only on the trial that suggested a benefit, the mean incremental cost was greater than $400,000 per QALY gained.

Discussion: Patients treated with aducanumab received minimal improvements in health outcomes at considerable cost. This resulted in incremental cost-effectiveness ratios that far exceeded commonly used value thresholds, even under optimistic treatment effectiveness assumptions. These findings are subject to the substantial uncertainty regarding whether aducanumab provides any true net health benefit, but evidence available currently suggests that an annual price of aducanumab of $56,000 is not in reasonable alignment with its clinical benefits.