Estimated generic prices for novel treatments for drug-resistant tuberculosis
Estimated generic prices for novel treatments for drug-resistant tuberculosis
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DOI：
10.1093/jac/dkw522
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发表时间：
2017-04-01
影响因子：
5.2
通讯作者：
Hill, Andrew
中科院分区：
文献类型：
--
作者：
Gotham, Dzintars;Fortunak, Joseph;Hill, Andrew
背景：据估计，全世界耐多药结核病年发病率为48万例，占结核病发病率的5%，但占死亡率的20%。最近已开发或重新利用多种药物治疗耐多药结核病。目前，耐多药结核病的治疗每个疗程花费数千美元。目的：估计在大规模竞争性生产的情况下可能实现的新型结核病药物的仿制药价格。方法：对利奈唑胺、莫西沙星和氯法齐明按每公斤原料药价格进行价格估算。其他成本也增加了，包括配方、包装和利润率。根据化学相似性，估计苏替唑胺的预计成本与利奈唑胺相当。通过评估合成路线、每公斤化学试剂的成本、合成路线和每步产率来估计贝达喹啉、德拉马尼和普雷托马尼的通用价格。成本计算算法反映了不同的监管要求和基于需求的规模效率，并通过测试对广泛获得的结核病药物的预测能力得到了验证。结果：贝达喹啉的仿制药价格估计为8- 17美元/月，delamanid为5- 16美元/月，pretomanid为11- 34美元/月，linezolid为4- 9美元/月，sutezolid为4- 9美元/月，氯法齐明为4- 11美元/月，莫西沙星为4- 8美元/月。估计仿制药价格比贝达喹啉低87%-94%，比德拉马尼低95%-98%，比利奈唑胺低94%-97%。STREAM试验改进的孟加拉国方案的仿制药价格估计为每疗程168- 395美元（目前费用为734- 1799美元），基于pretomanid的三药方案为53- 276美元，基于delamanid的四药方案为238- 507美元。结论：具有竞争性的大规模仿制药生产可以在当前采购预算范围内使耐多药结核病病例的治疗供应增加5-10倍。
Background: The estimated worldwide annual incidence of MDR-TB is 480 000, representing 5% of TB incidence, but 20% of mortality. Multiple drugs have recently been developed or repurposed for the treatment of MDR-TB. Currently, treatment for MDR-TB costs thousands of dollars per course.Objectives: To estimate generic prices for novel TB drugs that would be achievable given large-scale competitive manufacture.Methods: Prices for linezolid, moxifloxacin and clofazimine were estimated based on per-kilogram prices of the active pharmaceutical ingredient (API). Other costs were added, including formulation, packaging and a profit margin. The projected costs for sutezolid were estimated to be equivalent to those for linezolid, based on chemical similarity. Generic prices for bedaquiline, delamanid and pretomanid were estimated by assessing routes of synthesis, costs/kg of chemical reagents, routes of synthesis and per-step yields. Costing algorithms reflected variable regulatory requirements and efficiency of scale based on demand, and were validated by testing predictive ability against widely available TB medicines.Results: Estimated generic prices were US$8-$17/month for bedaquiline, $5-$16/month for delamanid, $11-$34/month for pretomanid, $4-$9/month for linezolid, $4-$9/month for sutezolid, $4-$11/month for clofazimine and $4-$8/month for moxifloxacin. The estimated generic prices were 87%-94% lower than the current lowest available prices for bedaquiline, 95%-98% for delamanid and 94%-97% for linezolid. Estimated generic prices were $168-$395 per course for the STREAM trial modified Bangladesh regimens (current costs $734-$1799), $53-$276 for pretomanid-based three-drug regimens and $238-$507 for a delamanid-based four-drug regimen.Conclusions: Competitive large-scale generic manufacture could allow supplies of treatment for 5-10 times more MDR-TB cases within current procurement budgets.