What they should do, in my view, is to make a

joint effort to persuade governments to introduce market entry rewards. A prize of $1 billion or more (as suggested by Jim O’Neill’s AMR report) for the development of new treatments to combat AMR would make a significant difference. Nevertheless, the present situation is quite posi-

tive. In spite of all the challenges, a handful of mainly small companies have antibiotic treatments in clinical trials against all three of the WHO Critical Priority Pathogens. A further 12 compa- nies have compounds which are active against one or two of these dangerous pathogens. There are increased levels of grants and fast track regulatory support. The first global public private partnership has been founded and has raised substantial sums of money for the development of antibiotic treat- ments for infections which the commercial sector is unlikely to cover. New antibiotics which are effective against the

Critical Pathogens will reach the market. How the market will respond is not clear. The optimistic view is that several of these will be blockbusters like Cubicin, in other words will earn a billion dol- lars or more per year. The pessimistic view is that they will struggle because it is fashionable to pay a low price for antibiotics. It is my view that some of these drugs will attain universal access for the poor, particularly for companies which have part- ners in low income countries. Whether these new antibiotics will be used in accordance with good stewardship is unknown at the present time. What is the 100-year plan for a pharmaceutical

industry which faces the complete destruction of the current repertoire of available antibiotics? The simple answer is that

there is no plan.

Unfortunately, bacteria do have a plan. This is to become resistant as quickly as possible to all new antibiotic threats. It has served them well for bil- lions of years. My view is that industry should have a long-

term plan. The plan must be to find treatments for AMR as quickly as bacteria do. For example, to focus on developing new monotherapies for AMR, and then throwing them away, is unsustainable for a 100 years. The plan should include old antibi- otics. The rejuvenated old antibiotic would only be used in combination with another antibiotic in order to reduce the emergence of resistance. Combinations could be two, three or even four

drugs, as is the case in tuberculosis therapy. Ultrafast diagnostics would be used to choose the correct combination. The current regulatory framework is much too slow to deal with AMR, which can arise in a few days. In order to populate


Professor Anthony Coates is the CSO of Helperby Therapeutics, leader of research teams, author of about 150 publications, recipient of numerous national and international grants from European Commission, British MRC, charities and industry, and named inventor on many patents. He is also the Professor of Medical Microbiology at St George’s University in London.

Dr Yanmin Hu obtained her PhD degree in the laboratory of Professor Coates in 1999. She start- ed her post-doctoral research with Professor Coates in St George’s Hospital Medical School, London. Now she is a Senior Research Fellow in St Georges University of London. Her scientific profiles are demonstrated by a stream of high pro- file publications.

Drug Discovery World Summer 2018

a new range of antibiotic combinations of old and new antibiotics, ultra-fast clinical trials are needed. For example, Phase I/II PK/PD with less patients than at present. In this way, it could be envisaged that a single old antibiotic could be rejuvenated several times in a 100-year period by combination with different antibiotics (sometimes called antibi- otic resistance breakers). That half of the 18 drugs in clinical development against Critical Priority Pathogens are combinations with betalactamase inhibitors supports the idea that rejuvenation of old drugs is feasible in the long term.

Conclusion Antibiotic discovery and development for resis- tant Gram-positive bacteria has been successful. For Critical Priority carbapenem-resistant Gram- negatives, the pipeline is inadequate, although the prospects are reasonably good for some drugs, even if they do not cover all of the prob- lem bacteria.


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