A lifeline for antibiotic development

Rarely has biomedical innovation been the focus of such public attention. As the world reels from the impact of the COVID-19 pandemic, the hope of nations is pinned upon researchers and industry successfully collaborating to get the treatments and vaccines the world needs.

And perhaps more than ever, the huge complexity and risks associated with medical advances are clear for all to see, as is the necessary political grappling to ensure sufficient funding and to make sure all advances fairly benefit those in need globally.

Yet, while urgent efforts are rightly directed towards our battle with COVID-19, we must not lose focus on other serious, long-term health issues. High on the list of acute concerns is the continuing global spread of drug-resistant infections, ‘superbugs’ which can no longer be effectively treated by existing antibiotics. As Dr Tedros, Director General of the World Health Organization (WHO), highlighted last month, this threatens to undo a century of medical progress, as bacteria develop resistance to the drugs that we have relied upon for years to treat them.

Last week’s launch of the near $1 billion industry-led AMR Action Fund marks a major and much-needed step forward in our struggle with this problem and promises to provide a shot in the arm for antibiotic development.

Like COVID-19, addressing antimicrobial resistance depends on scientific innovation. Yet, in spite of multiple calls for action over the past five years, we have yet to see more than a small handful of governments take seriously their responsibility to stimulate this crucial field. We have been left with a broken antibiotics market, offering only low prices and limited volumes to even breakthrough products, despite their enormous value to patients. Antibiotic development has become deeply unprofitable, with advances held back for decades.

This unfavourable commercial environment has seen most big pharmaceutical companies abandoning antibiotic research and development (R&D) programmes over the past decade or so. The numbers of antibiotics in development are perilously low as a result. There are currently just 41 in the clinical pipeline, a number which is meagre compared to any clinical field where the reward – or simply the political impetus – is greater.

Even for COVID-19, unknown to the world until the start of the year, more than 20 vaccine candidates are already in clinical trials, and nearly 40 possible therapies are being tested – all against a single pathogen. But for half of the dozen most deadly superbugs identified by the WHO as of the greatest concern, there are no more than two new antibiotics in clinical development which might be effective.

We have seen some action in response to this unfolding crisis. Initiatives like CARB-X, a funding partnership established between Wellcome and the US government four years ago and now also supported by the Gates Foundation and the British and German governments, has to date invested close to a quarter of a billion dollars into 65 promising very early-stage antibiotic R&D projects. The vast majority of these are in tiny biotech start-ups, nurturing the first green shoots of recovery in antibiotic R&D. Yet these pioneering companies have been facing a cliff edge.

The model of grant funding offered by CARB-X works well for early-stage innovation, where costs are relatively low, but risks are prohibitively high for private investors. Then, as these assets progress into bigger-scale development trials, the risks get lower while the costs rocket. In other areas of medical research, this is the point where private investors often take over from philanthropies and public agencies to provide funding.

For antibiotics, though, this has not been happening. With the market broken and failing to deliver dependable returns, private investors have increasingly shunned antibiotic R&D in favour of more lucrative areas. Antibiotic biotechs have become increasingly cash-starved – with some forced to file for bankruptcy – even as their promising new drugs reach market, leaving vital innovation to die on the vine.

The joint almost $1 billion commitment from the world’s leading major pharmaceutical companies to a new investment fund will offer targeted support to these small companies as they go into later-stage development.

Although the AMR Action Fund will act in many ways like a commercial investor, it will be able to finance projects currently neglected by venture capital, helping small biotechs survive and ensure antibiotics in development have a path to patients in urgent need. After years of accusations that they were acting irresponsibly by neglecting antibiotic R&D, this significant financial commitment by industry leaders shows they understand the importance of what is at stake.

It is not, however, the end of the story. The initial investment is a significant sum, but it will only sustain a fraction of the pipeline we need. Even with top-ups from public and philanthropic investors – and help from such partners to maximise impact in a challenging global health landscape – these resources realistically might only shepherd two or three new drugs to market.

Long-term sustainability still depends on governments stepping in to fairly incentivise the antibiotic innovation we all need. So far, the calls for them to do so have too often gone unheeded: now it is time for politicians to recognise that, like a COVID-19 vaccine, antibiotics are a medical innovation we can’t afford to live without.

A version of this article was first published in The Telegraph.