European Pharmaceutical Manufacturer editor Reece Armstrong looks at the antibiotics landscape and why we need to speak up about antimicrobial resistance (AMR).
In April this year, as the Covid-19 pandemic continued to dominate headlines across global media channels, the World Health Organisation (WHO) published its latest annual review evaluating the current clinical and preclinical pipelines for antibacterial candidates.
Conclusions from the report were stark, with WHO assistant director general on antimicrobial resistance (AMR), Dr Hanan Balkhy, saying that AMR is being fuelled by “the persistent failure to develop, manufacture, and distribute effective new antibiotics.”
A month prior, The Pew Trusts in the US updated its findings on the global pipeline of antibiotics and the conclusions were similar. With 43 antibiotics in clinical development - with some inevitably failing to win approval – it’s obvious that there are too few therapies in development to tackle the growing threat of AMR.
Of particular concern is how the larger pharmaceutical companies have completely taken themselves out of the picture when it comes to antibiotics. The Pew Trusts’ report says that of the 38 companies currently developing antibiotics, only two are classed as being among the top 50 pharma companies when it comes to commercial sales.
In 2016, AstraZeneca sold its antibiotics division to Pfizer in a deal worth over $500 million so it could focus on its three main therapy areas of respiratory & autoimmunity, cardiovascular & metabolic diseases, and oncology. Since then, the likes of Novartis, Sanofi and Allergen have exited the space to focus on disease areas which offer better return on investment (ROI).
The space then is dominated by smaller biotech companies, and with fewer resources than the major players, the market can be a volatile one to enter.
Biotech Achaogen gained regulatory approval from the FDA for its antibiotic plazomicin back in June 2018. Achaogen’s antibiotic was designed to treat complicated urinary tract infections (UTIs) caused by multidrug-resistant Enterobacteriaceae – a pathogen which is of critical priority for new antibiotics according to the WHO. However, a year later Achaogen was declaring bankruptcy and auctioning off its assets. It’s a story that has sadly been repeated by similar companies over the years and it’s a trend which points to one culprit as the catalyst.
The Market
Anyone following the discourse on antibiotics will know that for some time, pharmaceutical companies have been put off by the lack of ROI for developing new antibiotics. For instance, the Review on Antimicrobial Resistance chaired by Lord Jim O’Neill in 2014, shows that on average, it takes pharmaceutical companies 23 years to start achieving profitability for antibiotics.
Then there’s the looming threat of the patent life for antibiotics, or indeed any drug. When a new antibiotic launches onto the market, clinicians may be wary of using it lest resistance begins to develop. During this time, cheaper, generic antibiotics that still work against infections will be used instead. Indeed, the Review on Antimicrobial Resistance report states that whilst the total market for antibiotics is relatively large at $40 billion sales a year, only $4.7 billion of these sales come from patented antibiotics.
Compare this to oncology drugs for instance, which are used as first-line treatments once they reach the market and can make massive profits, and it’s understandable why pharma companies choose to invest elsewhere.
Next steps
With pharmaceutical developers put off from investing in new antibiotics, there is an obvious need for new solutions to incentivise the market so that new innovations can emerge.
For that to happen though, there needs be more interest put into the science underpinning antibiotic research – microbiology.
Lloyd Czaplewski, Chemical Biology Ventures’ director and someone who was on the advisory group for the WHO’s latest report sees the deficit of microbiologists as a major obstacle to antibiotic development.
“When I got into this space 20 years, most major pharma would have a team of 100 or 200 people working in the space – it’s all gone. That size and shape of team doesn’t exist in any one organisation any longer,” he tells me over a phone interview.
This has left antibiotic development work up to academics and a selection of biotechs, who don’t have a large enough portfolio to survive when a project fails.
“We don’t have the hundreds of people or thousands working in that space that we probably need for training, for career development, for longevity. Because you need to make fundamental discoveries to turn into new products. We don’t have enough of that,” Czaplewski adds.
It makes sense that there’s a deficit of microbiologist and infectious disease specialists. The Review on Antimicrobial Resistance highlights that in 2012, doctors in the US working in infectious diseases and HIV were the lowest paid compared to other medical fields. Move to 2021, and data from the National Residents Matching Program showed that 12% of infectious disease trainee positions in the US remain empty. For comparison, there were no positions left unfilled for oncology or pulmonary diseases in 2021.
Given how long it takes to find new drug discoveries and for drug development work to take place, promoting an interest in microbiology is needed if the industry is to have specialists at hand who can undertake work against AMR.
Action is needed now though, and thankfully we are seeing efforts. One of the major talking points in the WHO’s report is the AMR Action Fund. Set up by a range of pharmaceutical companies and investors, the AMR Action Fund has been designed to sustain antibiotic development funding by supporting smaller biotechs involved in the sector.
When asked about the funding situation for antibiotics, Dr Henry Skinner, the CEO of the AMR Action Fund told EPM:
“There’s no question that we need more capital to be funding innovation in this area from a number of fronts. It needs to be sustainable, and ideally market-driven. What we want to do is allow the innovation to advance, and to finance the best innovation that is developing the most critically needed products. And to do that in a sustainable way over a long period of time. That’s the goal – to really bring the market back here so that the best antibiotics are getting financed and advanced, and the best drugs for the greatest needs are getting to patients. That needs to come together organically with input from all sides – the public sector as well as the private.”
Funding is definitely key, but as the WHO’s reports states, many companies will not be able to survive once their products are registered, as new antibiotics are often held in reserve, something which can limit sales and make it difficult for companies to pay back investors.
But, as Czaplewski asks me during our interview, “do we have to make a profit for antibiotics?” The pharma industry would say yes, but international efforts such as the Large Hadron Collider and the International Space Station provide scientific benefits without explicitly selling a product, all in the name of science and the public good.
It’s food for thought but one thing is for certain, change needs to occur if we are to tackle AMR. Time will tell whether or not our current efforts are enough.