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The AMR crisis is solvable -- but we must act together and fast

Guest Commentary: Novo Nordisk Foundation chair calls on industry to respond with urgency to AMR crisis

Antimicrobial resistance is one of the most serious threats to humanity. This year, a staggering 700,000 people will die from infections that cannot be treated by most or all available antibiotics.

Sadly, this number will continue to grow in coming years, because our arsenal of antibiotics is running out and not enough new antibiotics are being successfully developed. The good news is that we can still act to prevent a doomsday scenario in 2050 where AMR is projected to cause 10 million deaths -- exceeding the current deadliness of cancer.

Contrary to cancer and climate change, the solutions are, if not simple, then at least straightforward: Better stewardship of our existing therapies and value-based reimbursement to unleash the vast potential of modern biology to create the next generation of antibiotics.

However, no one can solve it on their own. Hence, my plea to the pharmaceutical industry, to governments, to patients’ associations and to research communities and organizations is this: Act now and solve the AMR crisis together this decade.

“‘The AMR crisis’ is shorthand for a bleak future, returning to a pre-antibiotic era -- undermining many modern medicinal advances.”

Lars Rebien Sørensen, Novo Nordisk Foundation

Why would this take a decade? Because we are starting from a very difficult position.

Last decade, counterproductive incentives and broken business models saw investors and pharmaceutical companies flee the antibiotics space. The final defining mark of the decade came just before New Year’s when Melinta Therapeutics Inc. (NASDAQ:MLNT) filed for Chapter 11 -- seen by some as the tombstone of the fight against antibiotic resistance.

Meanwhile better surveillance of AMR is showing that the problem is growing exponentially across the globe. In addition to the overwhelming numbers mentioned above, data from CDC show an increase from 23,000 deaths in 2013 to 35,000 in 2019 in the U.S. alone. Even worse numbers from India show that more than 300,000 babies die from sepsis every year.

“The AMR crisis” is shorthand for a bleak future, returning to a pre-antibiotic era -- undermining many modern medicinal advances such as immuno-oncology, knee replacements, pacemakers and hundreds of other medical procedures, whose safety are underpinned by antibiotics that work.

Fortunately, this is avoidable with better stewardship of antibiotic usage and a total rethink of how modern societies should pay for life-saving antibiotics.

Much can be said about the need to control over-the-counter antibiotics, early diagnosis and prevention, the use of antibiotics for livestock, but most urgent of all is the need to create incentives for drug makers to develop novel and innovative antibiotics.

Rewarding market entry

Numerous independent groups of economists, legal scholars, NGOs and industry groups have concluded that market entry rewards are the right way to pay for antibiotics. Similar to having fire extinguishers, we pay to have them available, not per fire extinguished -- or in the case of antibiotics, per infection cured.

A good way to implement such a solution is through a subscription model in which revenue and volume of use are fully delinked. The U.K. is piloting such a “pull incentive” over the next few years.

Stakeholders will monitor this project with keen interest, but even if wildly successful, we must be mindful that it will realistically take at least three to five years to implement such a system across G20 countries.

Meanwhile, as I write, companies dedicated to creating and developing new antibiotics urgently needed by patients are going bankrupt and world-leading experts and researchers are fleeing the field. We need both short and long-term solutions.

“We need to expand and build on existing ‘push’ initiatives.”

Lars Rebien Sørensen, Novo Nordisk Foundation

We need to address several issues.

We need to work out how the U.K.’s subscription model, and a similar model in Sweden, can get under way in more countries at the fastest pace.

We need more frequent updating of standard of care protocols. Antibiotics are approved on a non-inferiority basis -- consequently, medical protocols are not updated when a better product comes along, undermining incentives to develop new treatments.

We need also to cater for government stockpiling of antibiotics for defense purposes, which would entail significant, upfront demand for novel antibiotics, guaranteeing companies a certain minimum sale of newly developed antibiotics.

Another model to address this could be through public-private benefit corporations, corresponding to low profit “utility companies,” where the public funds R&D, and private companies develop and market novel antibiotics, with the idea of ensuring a pricing environment that is fair and reasonable to patients, giving companies some return while securing the great benefits that antibiotics bring to society.

There is also a severe lack of funding for diagnostics in this field, an area that represents another broken business model and contributes to poor stewardship and mis-use of therapeutics. One organization addressing this is the non-profit CARB-X.

Better incentives

There need to be other incentives to lure the larger, established pharmaceutical industry back to the development of cutting-edge and revolutionary new antibiotics.

We need to expand and build on existing “push” initiatives. One example is the REPAIR Impact Fund -- an AMR initiative which the Novo Nordisk Foundation launched two years ago, and has now strengthened with a new strategic scope for the new decade. Having first focus on lead optimization to Phase I, this will now enable funding for Phase II trials as well.

The REPAIR Impact Fund backs academics and entrepreneurs in efforts we believe can revolutionize the future of the antibiotic resistance battle; companies founded in innovative science, driven by a clear product vision and led by strong management teams committed to delivering life-saving medicines in a changing regulatory environment.

As such, the ambition of the fund, when it was launched, was to invest $165 million over three to five years in start-ups, early-stage companies and corporate spinouts, focused on programs targeting high-priority pathogens as defined by the WHO and the CDC.

We believe that innovation is the key to longer-term success. That is why when we launched the REPAIR Impact Fund, we prioritized first-in-class therapies, covering small molecules, biologics and new modalities. Equally important, we targeted compounds between lead optimization and Phase I, the notorious ‘valley of death.” Today, the situation has deteriorated to a ‘desert of death’ covering all development phases.

This means that even if the eight companies we currently have in the REPAIR Impact Fund portfolio succeed and yield promising projects with solid Phase 1 data, there will be no one in the current panorama able to take them into later-stage clinical development.

For that reason, we took the decision to keep certain capital in reserve to support for our portfolio companies’ Phase II clinical trials.

In order to keep the threat of AMR at arm’s length, experts assess that the world needs one or two new antibiotics annually. Given that the expense of developing a new therapy is roughly $2 billion, we need incentives to generate $3 billion annually. In light of the multibillion-dollar budgets that the pharmaceutical industry allocates to R&D, this seems not only a manageable situation but a deliverable target.

Nevertheless, investors are losing hope that antibiotic development will ever generate a return. According to our analysis of data from GlobalData, the private venture capital flowing into antibiotics dropped by about 70% between 2016 and 2019.

To break this standstill and help disrupt the paradigm of the fight against AMR, the Novo Nordisk Foundation is hosting a session at World Economic Forum in Davos next week where we will bring together all stakeholders to discuss and hopefully agree on solutions and actions going forward.

When it comes to avoiding an imminent global public health catastrophe, stewardship and novel antibiotics are everything. Together, we can and must solve the antimicrobial resistance crisis.

Lars Rebien Sørensen is chairman of The Novo Nordisk Foundation and Novo Holdings A/S.

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