Expert Opinion on Drug Discovery | 2019
Steps to address anti-microbial drug resistance in today’s drug discovery
Abstract
There is no doubt that antimicrobial resistance (AMR) is one of the greatest health risks to emerge in the 21 century. The increase in multi-drug resistant strains of many bacterial pathogens raises the spectre of a post-antibiotic era in which previously treatable infections are fatal and routine surgery becomes a risky procedure. In response to the magnitude of the problem, the World Health Organization developed the priority list of AMR pathogens to aid in focusing resources and attention (Table 1) [1]. On this list multi-drug resistant Mycobacterium tuberculosis, which causes tuberculosis, is the highest priority since it has been the leading cause of death from an infectious disease for several years. Other priority pathogens on the critical list are carbapenem resistant Acinetobacter baumanii, Pseudomonas aeruginosa and Enterobacteriaceae. A major issue in the development of new antimicrobials has been the withdrawal of the large pharma companies from this field. The lack of a return on investment for antibiotics, and the difficulties in obtaining regulatory approval, has been well-documented and explains this. While biotechnology companies are active in the field, there is a funding gap between the early discovery and development work and clinical trials which has not been filled. A second consequence of pharma withdrawal is the loss of a wealth of industry expertise in antibacterial drug development, which cannot be easily replaced. A number of new incentives and initiatives have been launched in order to drive up interest; these include GARDP (Global Antibiotic Research & Development Partnership) and CARB-X (Combating Antibiotic Resistant Bacteria), which fund research and development, as well as incentives such as the Tropical Disease Priority Review Voucher Program, which can be applied to tuberculosis. The establishment of the Global Antimicrobial Resistance Research and Development Hub is a welcome addition, considering the large investment boost provided by the German government (500 million euros). However, the funding gap has not been closed and it remains to be seen whether these types of initiatives are sufficient to provide the economic and scientific stimulus required to generate the robust drug pipeline essential for attacking multiple pathogens. 2. Finding novel agents