Why more work is needed to fight antimicrobial resistance

Reece Armstrong speaks to Professor Janet Hemingway, CBE, about current efforts in tackling antimicrobial resistance.

The threat of AMR has been well documented in recent years. Perhaps the most notable effort came from the 2014 report “The Review on Antimicrobial Resistance” which was chaired by Lord Jim O’Neill and which outlined stark figures on the threat of AMR, most notably that by 2050, deaths attributable to AMR will rise to 10 million per year and that the economic burden of AMR will reach $100 trillion by 2050.

Add to this that the rise of AMR can bring about what the report calls a return to the ‘dark age of medicine’ where surgeries, cancer treatments, even childbirths, become staggeringly more dangerous when there is a lack of effective antibiotics, and it’s easy to understand why there’s such reason for concern. 

Since then, the issue hasn’t gone away, and these stark figures are brought up time and time again when arguments are made for more investment into the AMR sector. 

Professor Hemingway agrees that whilst the conversation surrounding AMR has largely remained focused on the same points, it’s part of those within the sector’s job “to keep it on the agenda”. 

As the founding Director of iiCON: Infection Innovation Consortium, CEO of iiDiagnostics, and Professor of Tropical Medicine at the Liverpool School of Tropical Medicine (LSTM), Professor Hemingway is very much a key figure in the space. And as a key figure, she understands that with drug discovery being such a contested field, both in terms of attracting funding and drawing the attention of government, making AMR a topic on everyone’s agendas is challenging.

“There will never be enough money to cover what you could do in this very broad health space. But if we don’t tackle this particular issue, it has ramifications right across the system,” she explains, stating that this is what needs to be brought to the attention of politicians and those who control funding.

iiCON specifically is a major advocate for work tackling AMR. It was founded in 2020 to connect industry, academia and the NHS and help discover and develop new treatments, including diagnostics, vaccines and preventative products for infective diseases. 

It’s doing this by collaborating with companies and providing access to expertise and facilities across 11 specialist research platforms that include things like organoid development, human challenge models, diagnostics, randomised controlled trials, hits to leads and more. 

Since 2020, iiCON has been especially busy, bringing at least 36 products to market ranging from personal hygiene products, medical devices, vaccines and preventative products that address infectious diseases and AMR. In terms of iiCON’s work in the drug discovery space Professor Hemingway says the organisation has got new drugs that have gone into Phase II clinical trials. 

“We’ve got three of those, either just completing Phase II clinical trials, or we’ll go into Phase II this year. We’ve got a vaccine that is going into a human challenge trial in Malawi, because it’s designed to go after one of the prevalent serotypes that doesn’t get caught by the current vaccines that is rife in Africa. If that works, we should be taking that into a large-scale population Phase III trial.”

So, a lot of effort on iiCON’s part but what about developments within the wider industry?  

Last year, there was activity within the AMR space in regard to developers attempting to bring new treatments to market.

The start of 2024 saw scientists from Roche and Harvard University identify a novel class of antibiotic that can target Carbapenem-resistant Acinetobacter baumannii (CRAB), which is one of the priority pathogens the World Health Organization (WHO) has identified as a major global threat. 

In studies, the molecule zosurabalpin, was found to kill multiple resistant strains of A. baumannii in culture, and, in mice, a strain resistant to all available antimicrobials.

This potential new antibiotic is different to current broad-spectrum antibiotics, in that it is specific to carbapenem-resistant A. baumannii and inhibits the LptB2FGC complex, the machinery that assembles the outer membrane of gram-negative bacteria. 

Another positive development came from researchers from the Massachusetts Institute of Technology (MIT) who used deep learning to identify a new class of antibiotic candidates that can kill methicillin-resistant Staphylococcus aureus (MRSA).

In regard to current pipeline developments, Hemingway thinks “it’s a really exciting time in the early discovery space.” The caveat to that though is she believes development is still going to hit a roadblock when companies start to move into clinical studies because that’s when costs increase, and more difficulties start to emerge. 

Another problem that the market currently faces is that it is dominated by small-medium-enterprises (SMEs), most of whom are single product companies, Hemingway tells me. What this means is they don’t have a portfolio of antibiotics to fall back on, because they can’t afford to have multiple products in development. 

Hemingway states that more thought needs to be put into how we can help ensure these companies are supported throughout that clinical phase.

“I think we need to be thinking about what happens with a lot of these things that come through and look really promising to stop them just grinding to a halt at that early discovery phase, and actually get them through to clinic in a format that we can really validate just how much of a game changer they really might be.” 

This is especially important given the lack of attention the AMR space has generated from the major pharmas. 

Whilst initiatives such as the AMR Action Fund, which aims to develop two–four new antibiotics by 2030, has received investment from the likes of Novartis, Takeda, Pfizer, Roche, and others, there is still a lack of R&D efforts by the larger companies, meaning that the task is being left to SMEs who face risks relating to cost and expansion. In fact, the 2023 “Antimicrobial Resistance Benchmark Opportunities” report states that SMEs are responsible for 75% of antibacterial and antifungal R&D. 

And whilst companies such as Pfizer and Shionogi have conducted acquisitions and partnerships to increase their pipelines and tackle resistant infections, it’s clear that there’s a strong need for large pharmas to invest in the sector and fuel the pipeline to tackle AMR. 

When talking about the bigger players in the industry, Professor Hemingway says: “They have been absent, notably absent for quite a long time. But these machines don’t move quickly, and they make their decisions commercially. And it won’t be a quick move back into this market, by those big companies, but I think we need to keep pushing them.” 

The healthcare sector is trying to make it more appealing for pharma companies to develop antimicrobials. The high cost of developing antibiotics and a poor return on investment has meant that the big pharmaceutical companies have opted out of antimicrobial research. Arguments have been made for push and pull incentives, in which funding is put forward to encourage the research and development of antibiotics regardless of their clinical success, and where new antibiotics that have proven scientific viability are rewarded as well. 

In 2020, the UK, through the National Institute for Health and Care Excellence (NICE) and NHS England, launched the Antimicrobial Resistance pilot to help incentivise pharmaceutical companies to develop new antibiotics. 

The pilot trialled a subscription-based approach where developers were paid a fee based on the value of the antibiotic over a fixed period, regardless of how much of the treatment was used. The maximum a developer could receive was £10 million per year. 

As part of that pilot, Shionogi and Pfizer were awarded contracts for the new antibiotics Cefiderocol and ceftazidime-avibactam that they developed. In 2023, the scheme was expanded so that annual payments for a contract could reach £20 million, when an antimicrobial met outstanding clinically-based criteria and represented exceptional value to patients and taxpayers. 

Speaking about the scheme, Professor Hemingway thinks that it’s helpful but for big pharma to get more involved within the sector, more needs to be done.

“I think you need some of the bigger markets to open up, I don’t think the UK market and the UK incentive on its own moves the dial enough for big pharma, they’re going to want the big global markets to open up.” 

“I think the incentives are not yet strong enough for industry, for big industry, to really say yes, this is a market we’re going to get back into wholeheartedly.” 

Professor Hemingway however does believe that we’re heading in the right direction, but a continual point of note throughout our conversation is this idea that there’s a more work to be done. 

“So I think we’re moving in the right direction, which is the positive side. But I think there’s still quite a long way to go. And we’re still in an arms race with the bugs that are continually becoming resistant. So the problem hasn’t gone away. We haven’t actually got the thing solved completely.” 

Professor Hemingway had hoped that Covid-19 might have stimulated more investment into this area, but with the investment landscape being overall quite tough for a lot of the life sciences industry right now, that hasn’t been the case. 

iiCON though is helping to lead the charge against resistant infections. The organisation was recently appointed by UK Research and Innovation (UKRI) to lead an initiative which will offer companies the chance to bid for funding to showcase their ideas for tackling infections and which is supported by £1.5 million in funding.

Other initiatives, such as the PACE partnership developed by LifeArc, a partner of iiCON’s, will see £30 million in funding become available to support early-stage innovation   against AMR. 

This is a major societal problem that could have serious consequences on global health. Whilst there is work ongoing, Professor Hemingway believes this message of how serious AMR is, should not just be on the minds of politicians and healthcare executives, but should be a concern for wider society, in a similar way to    how climate change has become a point of concern for younger people. 

“In many ways, it would be great if AMR became a cause for the younger generation because they’re the ones who are going to have to deal with the ramifications if we get this wrong. But it isn’t at the moment. They don’t see it. They don’t respond to it. They’re not being engaged in it. And so I don’t know how we move the dialogue, so it isn’t just in that drug developers and health care network, along with the political side, but is a much broader society discussion that’s going on.”

DDW Volume 25 – Issue 2, Spring 2024

Biography:

Prof Janet HemingwayProfessor Janet Hemingway CBE FRS is the former Director of Liverpool School of Tropical Medicine (LSTM). She is the founding Director of iiCON: Infection Innovation Consortium, CEO of iiDiagnostics, and Professor of Tropical Medicine at LSTM. Hemingway is a Past President of the Royal Society of Tropical Medicine and Hygiene.

 

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