Cost-Effectiveness of Daraxonrasib vs Chemotherapy in Previously Treated Metastatic Pancreatic Adenocarcinoma

Abstract Introduction: Daraxonrasib is the first broad RAS-targeted medicine approved for metastatic pancreatic adenocarcinoma. In RASolute 302, it approximately doubled median overall survival in the prespecified RAS G12 population. The US wholesale acquisition cost (WAC) is $39,800 per 30-day supply. Contemporary oncology launch prices have risen substantially, and many recently launched drugs have been priced above value-based benchmarks. The value of a genuinely transformative oncology therapy at this price is uncertain. Objective: To estimate the cost-effectiveness of daraxonrasib compared with investigators-choice chemotherapy in previously treated metastatic pancreatic adenocarcinoma using publicly available clinical and economic data. Design, Setting, and Participants: Economic evaluation using a 3-state partitioned survival model informed by the international randomized phase 3 RASolute 302 trial. Published Kaplan-Meier curves and numbers at risk were used to reconstruct pseudo-individual patient data. The RAS G12 population (n=459), corresponding to the trials dual primary efficacy end points, was the primary economic population; the overall randomized population (n=500) was analyzed in parallel. Analyses were conducted in 2026 from a US health sector perspective. Exposures: Daraxonrasib 300 mg orally once daily versus investigators-choice chemotherapy, weighted to the observed trial regimen distribution. Main Outcomes and Measures: Incremental life-years, quality-adjusted life-years (QALYs), costs, incremental cost-effectiveness ratio (ICER), incremental net monetary benefit, and the 30-day daraxonrasib price consistent with willingness-to-pay thresholds of $100,000, $150,000, $200,000, and $255,000/QALY. Costs were expressed in 2026 US dollars and discounted at 3% annually. Results: In the RAS G12 population, daraxonrasib generated 0.652 additional life-years and 0.506 additional QALYs at an incremental cost of $253,171, yielding an ICER of $500,637/QALY. The corresponding overall-population ICER was $542,255/QALY. A 10-year horizon changed the RAS G12 ICER to $497,270/QALY; using curve-specific distributions selected by Akaike information criterion produced $493,895/QALY. In 5000 probabilistic simulations, the probability of cost-effectiveness was 0% at $150,000 and $200,000/QALY and 0.1% at $255,000/QALY. Threshold prices in the RAS G12 population were $14,060 per 30 days at $150,000/QALY and $17,730 at $200,000/QALY, reductions of 64.7% and 55.5% from WAC. An independent secondary implementation using separately digitized survival curves and piecewise-exponential extrapolation produced a higher ICER; after calibrating drug exposure to observed treatment duration, the estimate remained approximately $676,000/QALY, with most of the difference attributable to the extrapolated treatment-exposure tail. Conclusions and Relevance: Daraxonrasib nearly doubled median overall survival in previously treated metastatic pancreatic adenocarcinoma, in which median survival with standard chemotherapy was about 7 months, and should remain available to eligible patients. At WAC, daraxonrasib costs approximately $500,000 per QALY, well above conventional US benchmarks. Because actual net acquisition prices may reflect confidential discounts or rebates, the ICER based on WAC may exceed the ICER at the net price. Threshold list prices consistent with $150,000-$200,000/QALY were $14,060-$17,730 per 30 days (a 55%-65% reduction from WAC), offered as reference points for pricing and coverage discussions rather than recommended prices.