Bent Estler, Hanna Fröhlich, Tobias Täger, Lutz Frankenstein
BACKGROUND: Transthyretin amyloid cardiomyopathy (ATTR-CM) causes heart failure with substantial morbidity, mortality, and healthcare utilization. ATTRibute-CM showed that acoramidis improves clinical outcomes, but its cost-effectiveness and budget impact in the German statutory health insurance (SHI) system remain uncertain. METHODS: We developed a cohort Markov model (lifetime horizon) discounting costs and outcomes at 3% annually. Overall survival was modeled with recalibrated Weibull functions fitted to randomized-phase ATTRibute-CM data and anchored to match month-30 survival. Health-related quality of life used Kansas City Cardiomyopathy Questionnaire Overall Summary (KCCQ-OS) trajectories mapped to EQ-5D utilities, with a plateau after 30 months in the base case. Direct medical costs (2025€) included drug, background management and hospitalization costs. Uncertainty was assessed with sensitivity analyses, scenario analyses and a budget impact analysis. RESULTS: Discounted mean lifetime costs were €13,881.50 (placebo) and €828,127.07 (acoramidis), for an incremental €814,245.57. QALYs increased from 2.743 to 4.029 (incremental 1.286) and life-years from 4.023 to 6.045 (incremental 2.022), yielding an ICER of €633,081 per QALY. Survival scenario analyses produced lifetime ICERs from €458,953/QALY in an optimistic scenario to €2,139,712/QALY in a pessimistic waning-benefit scenario. At a WTP of €100,000/QALY, the probability of cost-effectiveness was very low and results were driven primarily by acoramidis acquisition cost. In the budget impact analysis, year-1 SHI expenditure was €80,813,995, €134,689,992, and €269,379,983 for 30%, 50%, and 100% uptake, respectively. CONCLUSIONS: Despite benefits, acoramidis is unlikely to be cost-effective at current prices in Germany and could increase SHI spending. Price reductions could better align value with affordability.