Hillmen P, Jia X, Knight C, Sarda S, Mody-Patel N, Intorcia M, Dingli D. Model structure considerations for cost-effectiveness evaluation of C3 inhibitor pegcetacoplan versus C5 inhibitor in patients with paroxysmal nocturnal hemoglobinuria. Poster presented at the 2021 Virtual AMCP; April 2021.

BACKGROUND: Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, acquired, hematologic disease characterized by complement-mediated hemolysis. Pegcetacoplan, a C3 inhibitor, is undergoing evaluation in a phase 3 trial (PEGASUS; NCT03500549) in adult patients with PNH. Despite treatment with eculizumab (ECU), a C5 inhibitor, many patients experience residual anemia requiring transfusions. While economic disease modeling helps inform clinician decision-making, validating rare disease model structures remains difficult, with clinical expert opinion being essential to the process.

To develop a clinically appropriate model structure to evaluate the cost-effectiveness of pegcetacoplan vs ECU in PNH patients with anemia despite prior ECU treatment.

METHODS: Since no clear guidelines or systematic reviews currently exist for PNH, clinical (authors PH and DD) and economic expert interviews were conducted to understand natural history, clinical practice and economic considerations. Health states and outcomes evaluated for inclusion in the final model included transfusion dependence and avoidance, hemoglobin levels, hemolysis, and clinical practice considerations such as therapeutic risk-benefit analysis.

RESULTS: The final model structure was a lifetime Markov model that best simulated PNH disease course for patients with anemia despite ECU treatment. It covers two periods: during and after the 48-week trial period. Transfusion avoidance (a series of health states with different hemoglobin ranges), were designed to capture costs and quality-adjusted life years (QALYs). During the trial, patients (receiving ≥1 transfusion due to incomplete response) move between “Transfusion” and “No Transfusion” states. After the trial, the model replaces these states with a unique “Transfused” health state. Extrapolation of clinical data after the trial will be based on PEGASUS and expert opinions. EQ-5D utility weights will be estimated from the trial by mapping European Organization for Research and Treatment of Cancer QLQ-C30 quality-of-life data using published mapping algorithms. These utilities will be used to calculate QALYs. Cost estimates include drug and administration, health state, and adverse event costs. Indirect costs will be included for a scenario conducted from a societal perspective. The incremental cost-effectiveness ratio will be evaluated.

CONCLUSIONS: This is the first cost-effectiveness model comparing pegcetacoplan (C3 inhibitor) to ECU (C5 inhibitor) in PNH. It considers the most relevant outcomes reflecting disease course, clinical trials and treatment settings in PNH.

Share on: