Advancing New Drug Regimens for MDR/XDR TB

描述（由申请人提供）：全球出现的高度耐药结核病（MDR和XDR TB）对世界卫生构成了严重且日益严重的威胁。迫切需要新型结核病药物来对抗这些感染，但由2种或2种以上此类新型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，但这并不能为新方案的开发提供信息。此外，由于缺乏可行的市场，许多公司不敢开发治疗结核病的新药。该项目是大型制药公司，生物技术和学术界之间的独特合作伙伴关系，将研究一种新型的3种药物组合，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结核病适应症临床开发计划中。第三种是在临床开发中用于结核病以外的适应症，如果没有独立的支持，不太可能开发用于结核病。将对这种拟议的药物组合进行深入研究，以了解其快速杀死结核菌和防止耐药性出现的能力。这些特征以及最佳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完善的小鼠模型来确定，并与复杂的数学建模技术相结合。随着项目的发展，可能会纳入临床开发中的其他新药。目标是确定可能安全有效的强效药物组合，并随后在人体临床试验中进行测试。 迫切需要由两种或两种以上新药类别组成的新药方案，以应对高度耐药结核病（MDR和XDR TB）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个学术机构之间的独特合作伙伴关系，以研究一种由3种新药物组成的新型组合，预计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强效药物组合，并随后在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.