Presentation (CTI)

OBJECTIVES: Paroxysmal nocturnal hemoglobinuria (PNH) is an ultra-rare hematological disease characterized by chronic hemolytic anemia. In Brazil's private healthcare system, the standard of care is C5 inhibitors (C5i), with ravulizumab as the only option on the mandatory coverage list. Iptacopan is an oral factor B inhibitor used as monotherapy, and its efficacy in complement-inhibitor naïve patients was evaluated in the phase 3 trial APPOINT-PNH. This study evaluated the cost-utility of iptacopan versus C5i (eculizumab, ravulizumab, crovalimab) in treatment-naïve PNH patients.
METHODS: A semi-Markov model simulated the clinical course of PNH in health states for transfusion avoidance (with and without anemia), transfusion dependence, and death, over a lifetime horizon. Efficacy data for iptacopan were derived from APPOINT-PNH, while eculizumab/ravulizumab efficacy data were sourced from APPEX. Safety data for eculizumab/ravulizumab were obtained from Study 301. C5i parameters were used as a proxy for crovalimab, except for breakthrough hemolysis rates from COMMODORE-2. Health state utilities were derived from pivotal phase 3 trials of iptacopan. Direct medical costs, including drug list price, administration, prophylaxis, transfusion, and disease monitoring, were sourced from publicly available data and converted to USD. Model robustness was assessed using one-way sensitivity analysis and probabilistic sensitivity analysis.
RESULTS: Iptacopan dominated all comparators, achieving the highest total QALYs (13.429). Iptacopan provided QALY gains of 1.894 and cost savings of USD 833,647 versus eculizumab; 1.879 QALYs gains and USD 656,181 savings versus ravulizumab; and 1.896 QALYs gains with USD 3,802 in cost-savings versus crovalimab. The key drivers of the results were drug acquisition costs.
CONCLUSIONS: Iptacopan is an oral monotherapy and cost-saving alternative to C5i for complement inhibitor-naïve PNH patients in the Brazilian private healthcare system.