We need new antimicrobials to prevent the next infectious disease crisis

Imagine if scientists had seen Covid-19 coming years in advance yet did little to prepare. Unthinkable, right?

Yet that’s exactly what’s happening with another infectious disease crisis — the one caused by antibiotic-resistant bacteria and fungi. So-called superbugs already kill more than 700,000 people each year. And the World Health Organization warns that by 2050 the annual death toll could reach 10 million if we don’t use the time to get prepared.

The antibiotics and other antimicrobial drugs needed to prevent such a calamity don’t yet exist — and they’re years away from patients. The problem isn’t a lack of willing scientists, but rather a broken marketplace that has made it virtually impossible for researchers to attract adequate funding.

Unless lawmakers take steps to jump-start antimicrobial innovation, the world will soon find itself unprepared for a global health emergency as deadly as Covid-19.

Bacteria and fungi resistant to drugs have been around as long as the drugs themselves. When a patient takes an antimicrobial, microbes generally die. But some can survive, with the potential to become immune to existing antimicrobials.

In the past, scientists stayed ahead of deadly superbugs by inventing newer, more potent drugs. But innovation in antimicrobials has slowed dramatically in recent years, with higher rates of failure. In the last two decades, researchers have developed just two completely new kinds of antibiotics.

This slowdown has coincided with the widespread overuse of these medicines. Roughly one-third of antibiotic prescriptions are unnecessary, according to the Centers for Disease Control and Prevention. This overuse has led to an explosion of antibiotic-resistant bacteria.

The window for avoiding a superbug crisis that kills millions of people each year is closing quickly. Pulling back from the brink will require a two-pronged approach.

First, we must encourage doctors to prescribe antibiotics as smartly and sparingly as possible so patients take these drugs only when truly necessary. We must also educate patients about what antibiotics can actually do, what they can’t do, and their limitations. That will help slow the rise of antibiotic resistance, but it won’t stop it.

Second, we need a large-scale effort to create newer, more effective antimicrobials. That will require addressing the fundamentally broken market for these drugs.

Medicines are incredibly expensive to develop, with median R&D costs for a single antibiotic reaching $1 billion. Pharmaceutical companies can justify such investments only if they have a fighting chance to recoup their costs. But here’s the rub: A new, advanced antibiotic is reserved for emergencies, meaning a company would sell relatively few doses of it and almost certainly lose money.

That’s why pharmaceutical firms have moved away from antibiotic research in recent years. Four decades ago, there were 18 major drug companies pursuing new antibiotics. Today, there are only three.

A number of smaller biotech outfits have tried to beat the odds — but failed. Last year alone, two antibiotic startups declared bankruptcy despite having brought useful new antibiotics through to FDA approval. Others have been forced to shift to other research or sell their drug for pennies on the dollar to avoid the same fate.

Two reforms currently before Congress could help break this research logjam.

The Developing an Innovative Strategy for Antimicrobial Resistant Microorganisms (DISARM) Act would allow Medicare to pay hospitals more for using advanced antibiotics when appropriate. This would raise the demand for more sophisticated medicines, thus giving drug makers the confidence to invest in antibiotics research.

Another bill, the proposed Pioneering Antimicrobial Subscriptions to End Up Surging Resistance (PASTEUR) Act, takes a different tack. It would allow the government to pay a subscription for unlimited access to a new antimicrobial. This, in turn, would enable drug companies to recover their costs and an appropriate profit without having to sell large quantities of their drug, while ensuring that public health authorities have plenty of doses available, if needed.

The idea behind PASTEUR is similar to an idea proposed in 2016 by Jim O’Neill, the former chief economist of Goldman Sachs, when he suggested a one-time “market entry reward” of $1 billion for the development of a truly novel antimicrobial in a report on antimicrobial resistance commissioned by the British government. This idea — what economists call a pull incentive — is soon to be tested in the United Kingdom but not yet in any other G20 country.

America’s pharmaceutical industry is also prepared to bridge the gap. More than 20 of our country’s leading drug companies recently helped launch the AMR Action Fund, a partnership to invest more than $1 billion in antibiotic research and development with the goal of supporting later stages clinical trials so that two to four new antibiotics would reach approval by 2030.

But these companies can’t go it alone, and the antibiotics they develop won’t be available to patients unless the companies can stay in business. To ensure lifesaving antibiotics are available to us all will require cooperation from Washington. Lawmakers must act to improve the pipeline of new antimicrobial drugs — and quickly.

If they don’t, the world could soon face an infectious disease crisis as formidable as Covid-19.

Kevin Outterson is the founder and executive director of CARB-X and a professor at Boston University School of Law. CARB-X is a global nonprofit partnership that focuses on supporting the developers of promising new antibiotics, diagnostics, and vaccines; it is funded by BARDA, the Wellcome Trust, and the National Institute of Allergy and Infectious Diseases. John Rex is the chief medical officer at F2G Limited, a company focused on treatments for rare fungal diseases, and the founder of AMR Solutions. Both Outterson and Rex are members of the scientific advisory board of the Partnership to Fight Infectious Disease. The opinions expressed are their own and not necessarily those of their companies or organizations.