2022-12-19

Is Legislation to Safeguard Americans Against Superbugs a Boondoggle or Breakthrough?

With time running out in the 2022 congressional session, a bipartisan coalition of lawmakers and infectious disease specialists is scrambling to pass a bill aimed at spurring the development of antibiotics to combat the deadly spread of drug-resistant pathogens.

The PASTEUR Act, as amended, would provide $6 billion in federal funding over several years to give drugmakers incentive to develop and manufacture lifesaving medications for the small but growing number of infections highly resistant to antibiotics.

A range of supporters in the health care and drug sectors say the measure would fix the “broken market” for antibiotics by providing stable funding for an industry that tends to focus its research on areas considered good business opportunities. In recent years, most major drug companies have abandoned antibiotic development due to lackluster sales, and several smaller ones involved in the work have declared bankruptcy.

But the measure also has staunch critics in the medical community who deride it as a multibillion-dollar boondoggle and giveaway to Big Pharma. They argue it won’t solve the longer-term problem of relying on profit as the primary motive to discover and develop antibiotics.

“This is a very clever maneuver to get the taxpayers to bail out an industry that’s foundering,” said Dr. Brad Spellberg, an infectious disease specialist and the chief medical officer at the Los Angeles County+USC Medical Center. “If the government is going to spend money on this, it should spend it smartly.”

The PASTEUR Act, which stands for Pioneering Antimicrobial Subscriptions to End Upsurging Resistance, was introduced by Sens. Michael Bennet, a Colorado Democrat, and Todd Young, an Indiana Republican, and in the House by Reps. Mike Doyle, a Pennsylvania Democrat, and Drew Ferguson, a Georgia Republican. It has more than 65 bipartisan co-sponsors across both chambers.

People for and against the bill agree that antimicrobial resistance is a critical problem the federal government needs to address. Superbugs that can’t be treated kill more than 35,000 Americans and an estimated 1.27 million people worldwide each year.

While pharmaceutical companies can make billions on medications that patients take for months or years, such as cancer therapies and cholesterol-lowering drugs, the industry often loses money on antibiotics, which are prescribed for only a few days or weeks, said Amanda Jezek, senior vice president for public policy and government relations at the Infectious Diseases Society of America.

Hospitals are trying to administer fewer antibiotics, whose use stimulates the growth of resistant organisms, and are particularly hesitant to employ newer antibiotics that target bugs highly resistant to drugs. That’s because such bacteria infect a minority of patients, and using the new drugs widely would only cause more mutations and resistance, Jezek said.

“When someone makes a new antibiotic, the first thing that infectious disease doctors say is, ‘Don’t use it,’” said Dr. Amesh Adalja, a senior scholar at the Johns Hopkins University Center for Health Security, who helps oversee antibiotic use at his hospital. “We need to save it until we really need it, because we don’t want to lose this drug.”

Instead of paying by the pill for antibiotics — a practice that encourages companies to promote their use — the PASTEUR Act would allow the federal government to advance lump sums for promising FDA-approved drugs that could then be administered to patients covered by government insurance programs such as Medicare and Medicaid. Such payments would provide manufacturers enough income to cover their costs for these drugs, even if they were rarely used.

But critics, including Public Citizen, say the PASTEUR Act offers the pharmaceutical industry what amounts to a windfall, without standards rigorous enough to ensure that new drugs are really safer and more effective than existing ones. And they cite a recent study that showed the vast majority of hospital deaths in patients with invasive bacterial infections were caused by treatable bugs, often in very old or frail patients.

Opponents also argue that drugmakers already have access to financial incentives to create antibiotics. Federal agencies including the National Institutes of Health and the Biomedical Advanced Research and Development Authority have invested hundreds of millions of dollars during the past decade in antibiotics research. Drugmakers also have access to financing from nonprofits such as CARB-X and Wellcome, as well as public-private partnerships such as the AMR Action Fund.

Congress and the FDA in recent years have made it easier for companies to get antibiotics approved and extend their marketing exclusivity.

The problem is not funding, but rather a lack of vigorous approval standards at the FDA, said Dr. Reshma Ramachandran, an assistant professor at the Yale School of Medicine.

The FDA approved 15 new antimicrobial drugs between 2016 and 2019. But a recently published study indicates these drugs often appear no more effective than older medications, even as companies charge up to 100 times more for them.

That explains why these drugs don’t sell, said Dr. John Powers, a former FDA official, clinical professor at George Washington University School of Medicine, and one of the study’s authors. “Insurers aren’t paying, doctors aren’t using them, because the evidence doesn’t show patients do better on them than older drugs.”

Powers argued that FDA reviews of new antibiotics don’t put enough emphasis on how they benefit patients. In one clinical trial of cefiderocol, for example, the drug was better at killing bacteria, but 34% of patients taking it died, compared with 18% taking older drugs. The FDA approved cefiderocol under a policy that allows approval of new drugs even if trials show they are less effective than old ones by as much as 10%.

“We need evidence these drugs improve patient outcomes,” Powers said. “They may kill more bacteria, but doctors don’t treat bacteria, doctors treat patients.”

Spellberg and other researchers have proposed an alternative. A federally funded nonprofit, or several nonprofits, endowed with $1 billion to $2 billion, could fund antibiotic research for decades, Spellberg predicted. A board made up of patient advocates, doctors, industry representatives, and others would regularly update an official list of which pathogens to target, aiming to ensure taxpayer dollars are being used where most needed.

Each nonprofit would include microbiologists, medical chemists, and pharmacologists “all under one roof,” Spellberg added. “They would not focus on one drug, per se. They would focus on discovering and developing new, impactful technologies.”

Supporters counter that the PASTEUR Act already includes built-in quality controls.

The bill would create a committee, similar to the board that Spellberg proposes, to identify the most dangerous superbugs. PASTEUR also would fund $500 million in federal grants to help hospitals improve stewardship of antibiotics — programs that manage their use with an eye to preventing the spread of resistant organisms — prioritizing rural and safety-net hospitals that serve low-income patients.

The United Kingdom has adopted a similar program, which supporters hope could demonstrate the effectiveness of subscription models.

Even supporters of PASTEUR, such as Dr. Thomas Frieden, a former director of the Centers for Disease Control and Prevention, note that antimicrobial resistance is a complex, long-term problem to be attacked on multiple fronts.

Hospital controls on antibiotic use have dramatically reduced the prevalence of one class of “nightmare bacteria,” the carbapenem-resistant Enterobacterales. Other tools, such as new vaccines, could reduce bacterial threats, he said. Doctors also could prescribe fewer antibiotics if they had rapid tests to allow them to quickly distinguish between viral and bacterial infections, and to determine which bacteria have mutations requiring a special approach.

“The idea here is not to come up with one superior best antibiotic,” said Dr. Cornelius Clancy, a University of Pittsburgh professor of medicine who supports the PASTEUR Act. “The point is to have a pipeline.”

KHN (Kaiser Health News) is a national newsroom that produces in-depth journalism about health issues. Together with Policy Analysis and Polling, KHN is one of the three major operating programs at KFF (Kaiser Family Foundation). KFF is an endowed nonprofit organization providing information on health issues to the nation.