Cost-effectiveness of zenocutuzumab-zbco across three NRG1 fusion-positive indications
Glen J. WeissIntroduction
Zenocutuzumab-zbco is the first approved therapy for NRG1 fusion-positive cancer, indicated for non-small cell lung cancer (NSCLC), pancreatic ductal adenocarcinoma (PDAC), and cholangiocarcinoma (CCA). At the pivotal analyses, overall survival (OS) was unreported for NSCLC and PDAC, whereas a later publication reported observed OS and progression-free survival (PFS) for CCA. Cost-effectiveness was evaluated from a US payer perspective.
Methods
A three-state partitioned survival model estimated incremental costs and quality-adjusted life-years (QALYs) over 5 years. For NSCLC and PDAC, OS was modeled as a threshold variable across prespecified scenarios, with an incremental cost-effectiveness ratio (ICER) per scenario. For CCA, OS and PFS were reconstructed from published Kaplan-Meier curves and used directly, with a base-case ICER and extrapolation sensitivity. The wholesale acquisition cost was $24,155.46/infusion. Probabilistic, one-way, and threshold analyses were performed.
Results
For NSCLC and PDAC, ICERs ranged from approximately $665,000 (PDAC, OS 18 months) to $2.79 million per QALY (NSCLC, OS 10 months). For CCA, using observed data, the base-case ICER was approximately $397,000 per QALY (extrapolation range $349,000-$430,000). No indication was cost-effective at $150,000 or $200,000 per QALY. Drug acquisition cost, comparator OS, and utilities were the dominant drivers. Cost-effectiveness required acquisition-cost reductions of 60% to 91%.
Conclusions
At its current price, zenocutuzumab is not cost-effective for any approved indication, whether OS is unobserved (NSCLC, PDAC) or observed (CCA). Cost-effectiveness is achievable only through substantial price reduction. NSCLC and PDAC findings are conditional on the prespecified OS scenarios; CCA findings rest on observed survival with extrapolation.