The increasing threat of antimicrobial resistance

Antibiotics are losing their efficacy, and without them, modern healthcare won't be able to function — at least not the way we know it. Without the oft-prescribed pills, routine surgery, organ transplants, chemotherapy for cancer, will all take on a higher level of risk.

Each year, 700,000 people worldwide die of antimicrobial resistant (AMR) infections. By 2050, 10 million lives could be lost, with a cumulative cost of $100 trillion, and the catastrophe is likely to have a greater impact on the developing world.

"Not enough people have thought about this as a financial and economic challenge," says David Williams, Discuva CEO. "There has been very little focus on the economic benefit of stopping AMR."

These were all issues explored in a recent report from consulting firm PricewaterhouseCoopers, Antimicrobial resistance: The state of the nation report on UK R&D, that was launched at the 2016 Bioinfect Conference in early November. While the conference had a UK focus, it's a global problem. 

Taking action

Why has this happened? It's a result of many years of overusing and misusing antibiotics — both in human health and global agriculture — explained Derek Butler, chair of MRSA Action UK, who noted that bacteria are simply very good at resistance and resilience.

There are two sides to the answer — reducing the use of antibiotics, and developing new ones, and each is as important as the other.

"The demand side needs to be reduced, otherwise there is no point in developing new drugs," said Lord Jim O'Neil, who led the UK government's review into antimicrobial resistance. "By 2020, antibiotic prescriptions should be based on state-of-the-art diagnostics."

Reducing overuse will require engaging the public and physicians. Educating the public not to ask for antibiotics for coughs and colds, and educating general practitioners, surgeons, oncologists and others who prescribe antibiotics to be aware of the value of antibiotics and the risk of resistance.

It will also mean looking at prevention of infection, for example the development of vaccines, and tailoring treatment to make sure that the right antibiotic is given at the right time for the right bug. This will need the development and use of diagnostics to identify the infection and its antibiotic susceptibility. 

The challenge of drug development

Developing new drugs has become challenging. Jo Pisani of PwC, who authored the antimicrobial resistance report, has seen a linear decline in the number of FDA approvals for new antibiotics between 1983 and 2002, alongside a decline in activity from the big pharma companies.

In her report, looking at R&D in the UK, there were 78 players in the R&D space, but the majority of these were academic research labs and smaller biotech companies. Of the big pharma players, the only ones working in later stage research are Roche, AstraZeneca, GlaxoSmithKline and Merck & Co.

Yet, late this summer, AstraZeneca sold its anti-infective portfolio to Pfizer in a deal worth $1.6 billion. That transaction is expected to close in the fourth quarter and signals another player pulling out of the space. 

"It's important that there is still an end-market of potential partners for biotechs and drug discovery companies, as it is costly to take drugs through to the market," says Neil Murray, CEO, Redx Pharma.

This isn't just a U.K. situation, as Joe Larson, deputy director of the U.S. government-funded Biomedical Advanced Research and Development Authority (BARDA), pointed out, as there are 37 antibiotic candidates in development in the U.S. in Phase 2/3 compared with over 500 candidates in oncology.

In the works

There are some smaller start ups and biotechs in the U.K. that are working on developing antimicrobials that will fill the gap in the pipeline. Drug discovery company Discuva uses its TarGET (Targeted Genome Evolution Technologies) platform, which incorporates next generation sequencing, high-throughput functional genomic mutations, analysis and intelligent algorithms to understand the processes within microbes. 

NovaBiotics is developing antibiotic potentiators that act as add-ons to antibiotic treatment. By reversing resistance, these could increase the useful lifetime of existing antibiotics, and even bring long-unused antibiotics back into use.

While Nylex, another molecule in development with NovaBiotics, has some antibiotic activity itself, its focus is as an antibiotic potentiator, also known as a resistance breaker, which could be used as an adjunct to a variety of antibiotic classes. 

Rather than developing antimicrobials, Absynth Biologics is developing vaccines and antibodies against bacterial infections.

"Antibiotics put selection pressure onto the bacteria, but vaccines don't cause resistance to arise. This means that there is a strong economic argument to develop vaccines," says Fiona Marston, CEO, Absynth Biologics. "There is a reduction in the number of infections after a vaccine is introduced, and so the cost of vaccines is a small price to pay.

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Filed Under: Drug Discovery Regulatory / Compliance
Top image credit: Flickr; NIAID