Hill Andrew, Khoo Saye, Fortunak Joe, Simmons Bryony, Ford Nathan
Department of Pharmacology and Therapeutics, Liverpool University, United Kingdom.
Clin Infect Dis. 2014 Apr;58(7):928-36. doi: 10.1093/cid/ciu012. Epub 2014 Jan 6.
Several combinations of 2 or 3 direct-acting antivirals (DAAs) can cure hepatitis C virus (HCV) in the majority of treatment-naive patients. DAAs for HCV infection have similar mechanisms of action and chemical structures to antiretrovirals for human immunodeficiency virus (HIV) infection. Generic antiretrovirals are currently manufactured at very low prices, to treat 10 million people with HIV/AIDS in developing countries.
Four HCV DAAs, currently either in phase 3 development or recent approval (daclatasvir, sofosbuvir, simeprevir, faldaprevir), and ribavirin were classified by chemical structure, molecular weight, total daily dose, and complexity of synthesis. The likely range of manufacturing costs per gram of DAA were then projected as formulated product cost, based upon treating a minimum of 1 million patients annually (to arrive at volume demand) combined with an analysis of the complexity of synthesis and a 40% margin for formulation. Projections were then compared with actual costs of antiretrovirals with similar structures.
Minimum manufacturing costs of antiretrovirals were US$0.2-$2.1 per gram. The complexity of chemical synthesis for HCV DAAs was ranked from lowest to highest: ribavirin, daclatasvir, sofosbuvir, faldaprevir, and simeprevir. Predicted manufacturing costs (US dollars) for 12-week courses of HCV DAAs were $21-$63 for ribavirin, $10-$30 for daclatasvir, $68-$136 for sofosbuvir, $100-$210 for faldaprevir, and $130-$270 for simeprevir.
Within the next 15 years, large-scale manufacture of 2 or 3 drug combinations of HCV DAAs is feasible, with minimum target prices of $100-$250 per 12-week treatment course. These low prices could make widespread access to HCV treatment in low- and middle-income countries a realistic goal.
2种或3种直接作用抗病毒药物（DAA）的几种组合可治愈大多数初治丙型肝炎病毒（HCV）患者。用于HCV感染的DAA与用于人类免疫缺陷病毒（HIV）感染的抗逆转录病毒药物具有相似的作用机制和化学结构。目前，仿制药抗逆转录病毒药物的生产成本非常低，足以治疗发展中国家的1000万艾滋病毒/艾滋病患者。
4种目前处于3期开发阶段或近期已获批的HCV DAA（达卡他韦、索磷布韦、西米普韦、法达普韦）以及利巴韦林，按照化学结构、分子量、每日总剂量和合成复杂性进行分类。然后，根据每年至少治疗100万名患者（以达到批量需求），结合合成复杂性分析和40%的制剂利润，将每克DAA的可能制造成本预测为制剂产品成本。然后将预测结果与结构相似的抗逆转录病毒药物的实际成本进行比较。
抗逆转录病毒药物的最低制造成本为每克0.2 - 2.1美元。HCV DAA的化学合成复杂性从低到高排序为：利巴韦林、达卡他韦、索磷布韦、法达普韦、西米普韦。HCV DAA 12周疗程的预测制造成本（美元）为：利巴韦林21 - 63美元，达卡他韦10 - 30美元，索磷布韦68 - 136美元，法达普韦100 - 210美元，西米普韦130 - 270美元。
在未来15年内，大规模生产2种或3种药物组合的HCV DAA是可行的，每12周治疗疗程的最低目标价格为100 - 250美元。这些低价可能使低收入和中等收入国家广泛获得HCV治疗成为一个现实目标。
