Advancing New Drug Regimens for MDR/XDR TB

描述(申请人提供)：高度耐药结核病(耐多药结核病和广泛耐药结核病)在全球范围内出现，对世界卫生构成严重和日益严重的威胁。迫切需要新类别的结核病药物来对抗这些感染，但由2种或更多这种新类别的结核病药物组成的新方案被认为具有最大的长期成功机会。目前的模式是单独研究新药，但这并不能为新疗法的发展提供信息。此外，人们认为缺乏一个可行的市场，这阻止了许多公司开发治疗结核病的新药。该项目是大型制药公司、生物技术公司和学术界之间独特的合作伙伴关系，将研究一种新型的3种药物组合的新药，其中2种药物攻击细菌细胞壁的不同成分，第三种药物阻止细菌蛋白质合成。其中两种药物目前正在单独的临床开发计划中，用于结核病的适应症。第三个是针对结核病以外的适应症的临床开发，如果没有独立的支持，不太可能开发用于结核病的药物。将对这种拟议的药物组合进行深入研究，以确定其快速杀死结核细菌和防止出现耐药性的能力。这些特征以及最佳的组合和给药方案将使用创新的液体培养和细胞培养系统以及与复杂的数学建模技术相结合的成熟的小鼠模型来确定。随着项目的发展，临床开发中可能会加入更多的新药物。目标是确定可能安全有效的有效药物组合，并在随后的人体临床试验中进行测试。 迫切需要由两个或两个以上新药物类别组成的新药物方案，以应对高度耐药结核病(耐多药结核病和广泛耐药结核病)造成的严重和日益严重的全球卫生紧急情况。该项目提出了一家大型制药公司、一家小型生物技术公司和两家学术机构之间独特的合作伙伴关系，以研究3种新药物的新组合，预计它们将对结核病细菌具有协同杀灭作用。目标是确定可能安全有效的有效药物组合，并在随后的人体临床试验中进行测试。

DESCRIPTION (provided by applicant): The global emergence of highly drug resistant tuberculosis (MDR and XDR TB) poses a serious and growing threat to world health. New classes of TB drugs are urgently needed to combat these infections, but new regimens comprised of 2 or more members of such new classes of TB drugs are thought to have the greatest chances of long-term success. The current paradigm is to study new drugs individually, but this does not inform the development of new regimens. Moreover, the perceived lack of a viable market has deterred many companies from developing new drugs for TB. This project is a unique partnership between big pharma, biotech and academia that will examine a novel 3-drug combination of new agents in which 2 drugs attack different components of the bacterial cell wall and the third blocks bacterial protein synthesis. Two of the drugs are currently in separate clinical development programs for a TB indication. The third is in clinical development for indications other than TB and would not likely be developed for TB without independent support. This proposed drug combination will be studied intensively to with regard its ability to rapidly kill TB bacteria and prevent emergence of resistance. These characteristics as well as the optimal combinations and dosing regimens will be determined using innovative liquid culture and cell culture systems and a well established mouse model in an effort integrated with sophisticated mathematical modeling techniques. Additional new agents in clinical development may be incorporated as the project evolves. The goal is to identify potent drug combinations that are likely to be safe and effective and that could be subsequently tested in human clinical trials. New drug regimens comprised of 2 or more new drug classes are urgently needed to combat the serious and growing global health emergency posed by highly drug resistant tuberculosis (MDR and XDR TB). This project proposes a unique partnership between a major pharmaceutical company, a small biotech company and 2 academic institutions to examine a novel combination of 3 new agents expected to have a synergistic killing effect against TB bacteria. The goal is to identify potent drug combinations that are likely to be safe and effective and that could be subsequently tested in human clinical trials.