The market for new antibiotics is effectively failing. No novel class of drugs for the most virulent and persistent infections, those caused by Gram negative bacteria, has entered the clinic for over 50 years, and the drugs we have are steadily, if slowly, becoming less effective. Earlier this year Dame Sally Davies, the outgoing Chief Medical Officer for England, described the threat of antibiotic resistance as ‘catastrophic’ and potentially as great as that from climate change. Peter Jackson, Executive Director of the AMR Centre in Alderley Park, UK, is among those who believe that the pharma industry, often castigated as villains in the drama of antibiotics versus bacteria, must have a large part to play in turning this situation round. He will discuss these issues further during a panel discussion on deal-making in antibiotic development at Genesis 2019.
The blockage in the antibiotic pipeline is certainly not caused by lack of innovation. One of the few encouraging antibiotic-related developments in recent years has been the growth in the number of innovative small companies working in this space, designing novel drugs to tackle some of the most challenging infections. Rather, as Jackson explains, “It is the reimbursement side of the market for AMR drugs that is broken: the reward available for antibiotic development and commercialisation falls considerably short of its cost”. This is illustrated acutely by the case of Achaogen, a California-based biopharma company that filed for Chapter 11 bankruptcy in April 2019 only months after its drug, plazomicin (Zemdri™) was licensed by the FDA for severe urinary tract infections. “The cost of getting this drug, a next generation aminoglycoside for a limited range of indications, to market vastly outweighed the potential rewards for the company”, adds Jackson.
Most of the recent innovation in antibiotic design and discovery is funded by public bodies and charitable foundations, which are increasingly opening their programmes to SMEs. The global not-for-profit accelerator CARB-X, based in Boston and funded by some of the biggest names in medical research worldwide, is investing $500M in the early-stage development of drugs, vaccines, diagnostics and other products to tackle the problem of antibiotic resistance directly. The problem here, however, is that word ‘early-stage’, as CARB-X only funds projects to the end pf Phase I clinical trials. Advanced clinical trials are too costly for small companies to run, so it can be argued that this merely pushes the blockage down the pipeline towards Phase II and Phase III. If it is to be unblocked completely, then it is likely that risk-averse Big Pharma will need to get back on board.
At Genesis, Jackson and Yoshinori Yamano from the Japanese pharma company Shionogi will present a new type of deal that may help do just that. The AMR Centre, which, like CARB-X, most often invests in a drug only as far clinical proof of concept, has partnered with Shionogi to take their new antibiotic from pre-clinical development to Phase II. “We have re-designed the clinical development pathway and supply chain to shave a year off the development of this drug and significantly reduce costs”, says Jackson. The early clinical trials will take place in the NHS clinical trials unit in Liverpool, and there is an option for the drug to be returned to Shionogi for Phase III and commercialisation; only time will tell the extent to which the resulting savings in time and cost can help this drug reach and then flourish in the marketplace.
Written by Dr Clare Sansom - Freelance Science Writer
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