By the year 2050, it is predicted that antibiotic microbial resistance (AMR) will kill 10 million people every year. A major driver being the unhindered use of broad-spectrum antibiotics in produce, animals and their byproducts, and in clinical settings. Soon, a future where AMR is the norm, rather than the exception, is not a question of if but when. Like the rise of climate change, alarms have been raised long ago about the dangers should rampant antibiotic use be left unchecked. Critical medical procedures such as organ transplantations, caesarian sections, cancer chemotherapy and other invasive surgeries that rely on effective antibiotics may soon become more infrequent due to fear of secondary infections. While organizations like the Canadian Antimicrobial Resistance Surveillance System (CARSS) are in place to monitor AMR support policy and programs, on a global scale, the actions being taken are but a drop in the ocean.
AMR is by no means a new phenomenon, though only recently have we started to encounter on such a widescale. In fact, microbes isolated from 30,000-year old permafrost were identified to already harbor antibacterial resistant genes. This shouldn’t come as a surprise given that these organisms have had to co-exist with fungi and plants, which naturally produce antibiotics to avoid the toxic by-products produced by bacteria. The widespread and uncontrolled use of these drugs that came with the golden age of antibiotic discovery has accelerated the rate at which microbes develop resistance, selecting for populations that are in turn, able to further propagate these resistance genes across various communities.
Governments and organizations have begun taking action through the implementation of legislation, research funds, and improvements in regulations in order to develop additional antibiotics while curbing current antibiotic use. However, despite all these efforts to improve our current drug discovery landscape, antibiotics are not a profitable venture compared to the ten top-selling drugs in 2018. For example, Stelara, indicated for Crohn’s disease and psoriasis, is on the low end, earning a profit of $5.7 billion USD in 2018. Humira, indicated for arthritis and a myriad of other inflammatory conditions, topped the chart with a net profit of $19.9 billion USD, rounding out the top ten at an average of $8.24 billion USD in profits. By comparison, recent antibiotics sales averaged less than $50 million within a two-year period. From the standpoint of a company that answers to their shareholders, clearly antibiotics aren’t profitable. It should be no surprise then that since the 1980s, the number of drug companies with antibiotic discovery programs has fallen from 25 to just three, leaving only: Pfizer, Merck Sharp & Dohme (MSD), and GlaxoSmithKline (GSK).
Instead, small biotech companies have begun to take over development of antibiotics. Despite their efforts, the commercialization of new antibiotics has been met with difficulty. Take for example Achaogen, which launched the antibiotic plazomicin in 2018 and within 8 months, filed for bankruptcy on April 15, 2019. This situation is not unique to Achaogen. From a large pharmaceutical company’s standpoint, compared to long-term drugs that are used to treat diabetes or asthma, the short-term prescription of antibiotics leaves much to be desired in terms of financial return. On top of that, the ability of bacteria to quickly adapt to the drug means companies must spend more on R&D in order to keep up with the evolutionary arms race.
While small companies are able to receive support from government agencies like BARDA (the Biomedical Advanced Research and Development Authority) and CARB-X (Combating Antibiotic resistant Bacteria Biopharmaceutical Accelerator), they still lack the financial resources to get drug candidates through late-stage clinical development – a necessary step towards market release. In total, a small company will need at least $1 billion USD and approximately 10 years to push their drug for commercial use, a task that is challenging if not impossible without support from larger organizations and funding sources.
Like climate change, the business of AMR is the business of the world. Though efforts in some countries like Canada and the UK are pushing towards better antibiotic practices, in other nations like China, India, and the US, the rampant use of antibiotics is done in the name of short-term profit. In the coming years, more people could die from microbial infections than from cancer. In the coming years, large scale reforms will be needed in order to revitalize the antibiotic market and the drug market in general — not an easy task for a world obsessed with financial profits.
Louis Ngai
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