Opinion | Superbugs Are Getting Stronger

Drug-resistant infections pose a growing threat to public health. We’re not prepared to meet it.

That’s because the development pipeline of new antibiotics to fend off superbugs has fallen off. Superbugs are strains of bacteria and fungi that have developed immunity to the medicines used to kill them. Antimicrobials are critical tools in our fight against these pathogens.

The problem is that we’re not developing nearly enough of them and many of the medicines we currently have are no longer effective. It’s imperative that we act now — and fast — to bolster our deteriorating defenses against these often serious and life-threatening infections.

The Dwindling Pipeline

There are only 64 antibacterial therapeutics currently in clinical development. That’s compared to 1,300 treatments in development for various cancers. Over one-third of antibacterial drug candidates target just two bacteria: Clostridioides difficile and Mycobacterium tuberculosis. That leaves only 44 drugs to target all other pathogenic bacteria.

In other words, the antibacterial pipeline is grievously small. And it’s shrinking compared to previous decades. In the last 35 years, just one antibacterial with a novel way to target bacteria has been approved. Comparatively, 18 new antibacterials with novel targets were approved by the FDA between 1940 and 1990.

Meanwhile, superbugs continue to grow stronger. New research estimates they claimed 1.27 million lives in 2019 — more than twice the estimated number of annual deaths just 5 years prior.

Put simply, we’re in the midst of a pipeline paradox. Why is our discovery and development of new antibacterials declining while new pathogens are on the rise?

The problem is not the lack of success in developing new treatments. In the past decade, antibacterial drugs in clinical trials were more than twice as likely to move from early human testing to FDA approval versus drugs for all other diseases.

Instead, the problem is a fundamentally unique, misaligned market for antimicrobials that makes innovating unviable for developers. This has real impacts for physicians and patients.

A Misaligned Market

Every time we use an antimicrobial, the target microbes have a chance to survive and become resistant. So, clinicians prescribe them only when needed. But this sound medical practice makes for poor economic incentives for private companies in a market system.

Take the experience of the biotech firm Achaogen, which secured FDA approval in 2018 for its novel antibiotic plazomicin (Zemdri), after 15 years of development. The medication treats infections caused by one of the most challenging superbugs, carbapenem-resistant Enterobacteriaceae.

While important for the overall armamentarium, such novel antimicrobials are used particularly sparingly to prevent dangerous pathogens from developing resistance to our strongest medications. As a result, clinicians hold novel antibiotics like plazomicin in reserve, using them judiciously to preserve effectiveness. That means companies like Achaogen don’t sell large quantities of the drugs they develop — or earn back the capital they invested in the research and development process.

Achaogen filed for bankruptcy in 2019. In the 3 years since, several other small biotech companies that successfully cleared the clinical pipeline with FDA-approved antibacterials have seen a similar fate.

The market conditions for antimicrobials are so discouraging that most large biopharmaceutical companies have pulled out of the sector entirely. Small companies discovered over 80% of the antibacterial therapeutics currently in clinical trials.

These dynamics are causing investors to vacate the antimicrobial sector, too. Venture capital funding for biotech firms focusing on antibacterial research declined over the last decade, while other areas such as oncology rose 700%.

That’s despite the fact that, if nothing changes, 10 million people worldwide could die of drug-resistant infections annually by 2050 — surpassing cancer as a leading cause of death.

The public health need is there, and it’s only growing more urgent. The market incentives are not.

What Can We Do?

Thankfully, solutions exist. More specifically, government intervention and incentives can help change the game for private companies to develop these medications. One solution is the bipartisan, bicameral Pioneering Antimicrobial Subscriptions To End Upsurging Resistance (PASTEUR) Act, which would change the current dose-based payment model for certain antimicrobials. Under PASTEUR, the government would offer developers of the most critically needed antimicrobials between $750 million and $3 billion up front in exchange for access to their medications once they hit the market. This approach pays for value over volume and provides developers with the predictable return on investment needed to fuel much-needed antimicrobial innovation.

Another bill under consideration is the Developing an Innovative Strategy for Antimicrobial Resistant Microorganisms (DISARM) Act. The legislation would increase Medicare reimbursements for certain antimicrobials, ensuring patients have access to the best novel antibiotics for their individual needs.

Superbugs are here to stay. We have policy solutions on the table that can help prevent them from taking a growing number of lives. It’s long past time to take action.

David Thomas, MS, is vice president of industry research at the Biotechnology Innovation Organization. Emily Wheeler is director of infectious disease policy at the Biotechnology Innovation Organization.