Product Development and Market Access Consulting, Fortrea, 4 Maguire Street, London, SE1 2NQ, UK.
Clin Drug Investig. 2024 Jun;44(6):399-412. doi: 10.1007/s40261-024-01363-1. Epub 2024 May 25.
Novel messenger RNA (mRNA)-based therapies, currently in development, are emerging as a promising potential treatment modality for a broad range of life-threatening and life-limiting inherited liver diseases, including methylmalonic acidemia (MMA) and propionic acidemia (PA). However, owing in part to their complexity, they are likely to come at considerable financial cost to healthcare systems. The objective of this research was to synthesize available evidence on the costs and clinical consequences associated with MMA and PA for the purpose of exploratory economic evaluation of novel mRNA-based therapies using an early cost-utility model from the United Kingdom payer perspective.
A Markov model was constructed to simulate the costs and outcomes associated with novel mRNA therapies, compared with a combination of dietary management and organ transplantation (standard of care) among hypothetical cohorts of new-born patients with MMA and PA. Key model drivers were identified, and a price threshold analysis was performed to estimate value-based price ranges for future mRNA therapies given willingness-to-pay thresholds for orphan diseases.
mRNA therapy was associated with an additional 5.7 and 1.3 quality-adjusted life-years (QALYs) gained per patient lifetime among patients with MMA and PA, respectively. Key drivers of cost-effectiveness were relative improvement in utility among patients who receive mRNA-based therapy and transplantation, and the cost of mRNA therapy. Assuming a willingness to pay range of £100,000-£300,000 per QALY gained, the model demonstrated mRNA therapy to be cost-effective in MMA and PA at an annual treatment cost of £70,452-£94,575 and £31,313-£36,695, respectively.
Despite the lack of a strong evidence base in MMA and PA, this model provides a useful tool to estimate the cost-effectiveness, and inform value-based pricing, of new mRNA-based therapies. Our analyses also identified areas for research that will have the greatest value in reducing uncertainty in future health economic evaluations of such treatments.
新型信使 RNA（mRNA）疗法目前正在研发中，有望成为治疗多种危及生命和生命有限的遗传性肝脏疾病的潜在治疗方法，包括甲基丙二酸血症（MMA）和丙酸血症（PA）。然而，由于其复杂性，这些疗法可能会给医疗保健系统带来巨大的经济成本。本研究旨在综合有关 MMA 和 PA 的成本和临床后果的现有证据，目的是从英国支付方的角度，利用早期成本效用模型对新型基于 mRNA 的疗法进行探索性经济评估。
构建了一个马尔可夫模型，以模拟新型 mRNA 疗法与 MMA 和 PA 新发病例患者的饮食管理和器官移植相结合（标准治疗）相关的成本和结果。确定了关键模型驱动因素，并进行了价格阈值分析，以根据为孤儿病设定的支付意愿阈值估算未来 mRNA 疗法的基于价值的价格范围。
与 MMA 和 PA 患者的标准治疗相比，mRNA 治疗分别使每位患者的终生额外获得 5.7 和 1.3 个质量调整生命年（QALY）。成本效益的关键驱动因素是接受基于 mRNA 的治疗和移植的患者的效用相对改善，以及 mRNA 治疗的成本。假设支付意愿范围为每获得 1 QALY 支付 100,000-300,000 英镑，该模型表明，在每年治疗费用为 70,452-94,575 英镑和 31,313-36,695 英镑时，mRNA 治疗在 MMA 和 PA 中具有成本效益。
尽管 MMA 和 PA 的证据基础薄弱，但该模型为新型基于 mRNA 的疗法的成本效益评估和基于价值的定价提供了有用的工具。我们的分析还确定了研究领域，这些研究将在降低此类治疗方法未来健康经济评估中的不确定性方面具有最大价值。
