Peterson Christopher, Paria Sayan, Deshpande Anita, Ahmad Saeed, Harmon Andrew, Dillon John, Laird Trevor
Latham BioPharm Group, Elkridge, Maryland, 21705, USA.
Medicines for All Institute, VCU, Richmond, Virginia, 23298, USA.
Gates Open Res. 2022 Feb 16;6:8. doi: 10.12688/gatesopenres.13509.1. eCollection 2022.
Orally delivered drugs offer significant benefits in the fight against viral infections, and cost-effective production is critical to their impact on pandemic response in low- and middle-income countries. One example, molnupiravir, a COVID-19 therapy developed by Emory, Ridgeback, and Merck & Co., had potential to benefit from significant cost of goods (COGs) reductions for its active pharmaceutical ingredient (API), including starting materials. A holistic approach to identifying, developing, and evaluating optimized synthetic routes, which includes detailed COGs modeling, provides a rapid means to increase the availability, uptake and application of molnupiravir and other antivirals in global markets. Identification and development of alternate processes for the synthesis of molnupiravir has been conducted by the Medicines for All Institute at Virginia Commonwealth University (M4ALL) and the Green and Turner Labs at the University of Manchester. Both groups developed innovative processes based on synthetic route design and biocatalysis aimed at lowering costs and improving global access. The authors then performed COGs modeling to assess cost saving opportunities. This included a focus on manufacturing environments and facilities amenable to global public health and the identification of key parameters using sensitivity analyses. While all of the evaluated routes provide efficiency benefits, the best options yielded 3-6 fold API COGs reductions leading to treatment COGs as low as <$3/regimen. Additionally, key starting materials and cost drivers were quantified to evaluate the robustness of the savings. Finally, COGs models can continue to inform the focus of future development efforts on the most promising routes for additional cost savings. While the full price of a treatment course includes other factors, these alternative API synthetic approaches have significant potential to help facilitate broader access in low- and middle-income countries. As other promising therapeutics are developed, a similar process could enable rapid cost reductions while enhancing global access.
口服给药在抗击病毒感染方面具有显著优势，而具有成本效益的生产对于其在低收入和中等收入国家应对疫情的影响至关重要。一个例子是莫努匹拉韦，这是由埃默里大学、Ridgeback公司和默克公司联合研发的一种治疗新冠肺炎的药物，其活性药物成分（API），包括起始原料，有可能从大幅降低的商品成本（COGs）中受益。采用整体方法来识别、开发和评估优化的合成路线，包括详细的COGs建模，为提高莫努匹拉韦和其他抗病毒药物在全球市场的可及性、使用率和应用提供了一种快速途径。弗吉尼亚联邦大学的全民用药研究所（M4ALL）以及曼彻斯特大学的格林实验室和特纳实验室已经开展了莫努匹拉韦合成替代工艺的识别和开发工作。这两个团队都基于合成路线设计和生物催化开发了创新工艺，旨在降低成本并改善全球可及性。作者随后进行了COGs建模，以评估成本节约机会。这包括关注适合全球公共卫生的生产环境和设施，并通过敏感性分析确定关键参数。虽然所有评估的路线都带来了效率提升，但最佳方案使API的COGs降低了3至6倍，从而使治疗COGs低至<$3/疗程。此外，还对关键起始原料和成本驱动因素进行了量化，以评估节约成本的稳健性。最后，COGs模型可以继续为未来的开发工作重点提供参考，以确定最有前景的路线，实现更多成本节约。虽然一个疗程的全价还包括其他因素，但这些替代的API合成方法具有显著潜力，有助于在低收入和中等收入国家促进更广泛的可及性。随着其他有前景的治疗方法的开发，类似的过程可以在提高全球可及性的同时实现快速成本降低。
