Over the past year we’ve watched two troubling trends escalate. First, patients increasingly face—and their doctors struggle to treat—infections that do not respond to existing antibiotics. Second, major pharmaceutical companies are backing away from developing new antibiotics. Last July, Novartis became the third major pharmaceutical company in 2018 alone to announce that it would end antibiotic research and development. Other companies that haven’t eliminated antibiotic R&D have made significant reductions.
In short, just as the world needs new and novel antibiotics, the research needed to find them is shrinking in size and scope.
Antibiotics play a central role in modern medicine—one that goes beyond treating infections that were routinely fatal before the drugs came on the scene in the mid-20th century. The discovery of penicillin and the drugs that followed also made possible surgery, chemotherapy, dialysis, and other procedures that we now take for granted. They also help protect at-risk patients such as children, seniors, and people who have underlying conditions, such as cystic fibrosis, that weaken the immune system.
The Pew Charitable Trusts and the Infectious Diseases Society of America, together with more than 20 leaders in antibiotic research and development, have joined forces to push for swift action in the face of the growing challenge posed by the combination of increasing resistance to antibiotics and decreasing efforts to find urgently needed new antibiotics. In a letter recently sent to members of Congress, our organizations called on policymakers to commit to advancing a set of economic incentives to make antibiotic development viable again.
Providing economic incentives to pharmaceutical companies might seem like a hard sell at a time when high drug prices are a top concern of the public and policymakers. Our two organizations share this concern, and Pew has been working to address the problem. However, antibiotics are unlike other drugs. As companies reduce or eliminate their research efforts, the antibiotic market is less likely to produce new therapies to meet the threat of increasingly resistant infections, and physicians will have fewer tools to cure infections and protect patients as they undergo medical procedures.
At least nine authoritative commissions and reports have come to the same conclusion, recommending “pull incentives” to reward the development of urgently needed antibiotics by increasing the return on a drug once it comes to market. We believe that the U.S. approach to pull incentives must:
- Address the greatest public health needs. The focus should be on stimulating the development of novel antibiotics to treat the most urgent threats.
- Align with efforts to improve stewardship and surveillance. Antibiotics must be used appropriately so as not to accelerate the emergence of resistance.
- Provide predictability. Any incentive needs to be structured in a way that ensures it will be available when an antibiotic developer meets eligibility criteria.
- Stabilize the market. Measures must be put in place to ensure that companies that have recently developed promising new antibiotics, often with the support of public funds, have an incentive to continue producing them.
According to one estimate, to fix the antibiotic market, a package of pull incentives should be worth an additional $1 billion in revenue for each qualifying antibiotic that a company develops, on top of sales earnings. The full amount would not need to come from the U.S., nor would it need to come exclusively from public sources. The U.S. contribution should be proportionate to the U.S. share of the global pharmaceutical market.
At a time when the cost of pharmaceuticals in the U.S. is already high, we do not suggest pull incentives lightly. But the antibiotic market is different from other drug markets in two important ways. When a new antibiotic is approved, public health requires that it be held in reserve as long as possible to slow the development of resistance. This means that new antibiotics often face anemic initial sales. For example, Allergan’s Teflaro—one of the very few drugs effective against multidrug-resistant pathogens that have been identified by the Centers for Disease Control and Prevention as serious threats to public health—garnered average annual sales of $130 million from 2016 through 2018. Contrast that figure with the $1.4 billion in sales generated last year by the 20th best-sellingcancer drug, and it isn’t surprising that Allergan announced plans last year to divest its anti-infectives business unit.
The second way in which antibiotics differ from other medications is that over time, bacteria will develop ever-greater resistance to existing drugs, rendering them ineffective and, making it inevitable that new antibiotics will be needed. When antibiotic development stands still, the options for patients go backward.
CDC data show that tens of thousands of Americans die each year because of resistant infections. The situation could quickly become exponentially worse if new, resistant mutations emerge. Indeed, alarming new types of antibiotic resistance have recently been identified—enabling pathogens to evade some of our most powerful antibiotics and spread quickly.
Private-sector investment in antibiotics has been falling for several decades, and there is no indication that the trend will slow. Public programs that support aspects of antibiotic development before they reach the market (often referred to as “push incentives”)—such as those of the Biomedical Advanced Research and Development Authority, the National Institutes of Health, and the Combating Antibiotic Resistant Bacteria Biopharmaceutical Accelerator (CARB-X) program—have been important steps forward, but not enough. We need to fundamentally change how the market for new antibiotics works.
We cannot afford to wait or hope any longer. Ensuring that the U.S. has effective antibiotics is not a luxury; it is a necessity for protecting medical advances, preventing the spread of drug-resistant pathogens, and saving lives. Congress must act now.
Allan Coukell directs health programs for The Pew Charitable Trusts. Helen W. Boucher, MD, is director of the Tufts Center for Integrated Management of Antimicrobial Resistance at Tufts Medical Center, professor of medicine at Tufts University School of Medicine, and a member of the Infectious Diseases Society of America board of directors.
This article first appeared in The Hill.