The public health implications of AMR have been known for years, but the number of people affected is just beginning to come into focus. A study published earlier this year in The Lancet estimated that 4.95 million deaths in 2019 were associated with AMR, including 1.27 million that were directly attributable to a drug-resistant infection. And data from the Centers for Disease Control and Prevention (CDC) show that US hospitals saw a 15% increase in infections and deaths from drug-resistant, hospital-acquired bacteria in 2020.
"More and more patients are being impacted by antibiotic resistance, and physicians do not have the tools they need to help take care of those patients," Jezek said.
While the public health value of antibiotics is unquestionable, they are not as profitable as other drugs. Unlike many other medications, antibiotics are used only for a limited time. And to prevent the development of resistance, new antibiotics are used sparingly and reserved mainly for infections that are resistant to older drugs. As a result, new antibiotics don't produce sufficient revenue for the companies that develop them.
This has led many large pharmaceutical companies to abandon antibiotic development altogether in favor of more lucrative drugs. And while there many small biotech companies that are developing innovative new antibiotics, research and development is costly. Discovering and developing a new antibiotic and successfully getting it through clinical trials and regulatory approval can cost well over $1 billion.
In recent years, groups like the Biomedical Advanced Research and Development Authority (BARDA) and the Combating Antibiotic-Resistant Bacteria Biopharmaceutical Accelerator (CARB-X) have emerged to provide financial "push" incentives that provide early-stage funding help cover some of the costs of developing of new antibiotics. This funding has been critical for getting antibacterial products into and through expensive clinical trials.
But with the limited return on investment from antibiotics, smaller companies struggle to survive even when they get new products approved by the FDA. According to a report earlier this year from the Biotechnology Innovation Organization, of the 12 antibiotics companies that have gone public over the last decade, only 5 are still active today.
These economic challenges have, in turn, led to a relatively thin pipeline of new antibiotics. According to the most recent World Health Organization (WHO) analysis, there are only 27 new antibiotics in development against the bacteria that the agency has deemed "priority" pathogens because of their resistance to current antibiotics and their ability to cause severe infections. Altogether, there are 77 antibacterial agents in clinical development.
In contrast, in 2020 there were more than 1,300 drugs medicine and vaccines in development for various cancers, according to an analysis by the industry lobbying group PhRMA.
A 'Netflix-style' model
That's the dilemma that advocates hope the PASTEUR Act could help solve. The bipartisan legislation, reintroduced in June 2021 by Sen. Michael Bennet (D-Colo.), Sen. Todd Young (R-Ind.), Rep. Mike Doyle (D-Pa.), and Rep. Drew Ferguson (R-Ga.), would authorize the Department of Health and Human Services (HHS) to enter into subscription contracts with companies that develop a "critically-needed antimicrobial" that targets infections identified by a congressionally appointed body of experts.
Under the contracts, the government would pay pharmaceutical companies anywhere from $750 million to $3 billion up front for patients covered by federal insurance programs (such as Medicare, Medicaid, and the Veterans Health Administration) to have access to a new antibiotic for 5 to 10 years. The bill would also establish a grant program under the CDC to support appropriate use of the antibiotics in hospitals.
Dubbed by some a "Netflix-style" model, the idea is similar to a program that's under way in the United Kingdom, where the National Health Service has agreed to pay up to £10 million ($12.4 million US) a year for up to 10 years for access to the antibiotics cefiderocol and ceftazidime-avibactam, manufactured by Shionogi and Pfizer, respectively. UK policymakers hope that paying an annual fee to drugmakers for new antibiotics will ease concerns about the return on investment and incentivize other companies to pursue antibiotic development.
David Hyun, MD, director of the Antibiotic Resistance Project at the Pew Charitable Trusts, says that a "pull" incentive that provides set funding based on the public health value of a new antibiotic, rather than on sales volume, will help provide a more stable return on investment for companies that develop new antibiotics.
"We view the PASTEUR Act as a really integral and essential component of the battle against antibiotic-resistant infections," Hyun said. "It's going to go a long way toward fixing the stagnant antibiotic development pipeline."
Pew and IDSA were among 165 organizations that recently sent a letter to congressional leaders calling on them to pass the PASTEUR Act.
"Novel antimicrobials must be used judiciously to limit the development of resistance, so payment based on volume fails to drive innovation," the letter stated. "PASTEUR's subscription model is an innovative way to pay for novel antimicrobials that will revitalize the pipeline and support appropriate use."