Dustin Brown, a slight, dark-haired guy who lives in southwest Indiana, is 36, married, and a stay-at-home dad. He never expected to achieve any of those milestones: wife, toddler son, moving away from his family in Kentucky. Not even adulthood. Brown has cystic fibrosis, an inherited disorder that clogs major organs with sticky, sludgy mucus and makes them breeding grounds for infections. When he was born, newly diagnosed patients weren't expected to survive past elementary school.
That the roughly 40,000 CF patients in the US have managed to beat that prediction is due to better treatments—just three years ago, the US Food and Drug Administration (FDA) fast-tracked a new drug combination to address the effects of the underlying genetic mutation—but also to hard work. Every day, Brown follows a tailored regimen of exercises, supplements, and pharmaceuticals to keep down the disease's worst effects. That includes antibiotics: inhaled, in pills, and several times a year, through a catheter threaded up a vein into his heart. Brown calls taking care of his health "a full-time job."
Still, he's losing ground. The mucus in Brown's lungs harbors Pseudomonas aeruginosa, bacteria that cause serious infections in people whose immune defenses are impaired. If that simmering occupation flares up into pneumonia, the results could be deadly, because tests by his doctors have shown that Brown's strain of Pseudomonas is fully resistant to four antibiotics and partially resistant to two more. Brown has already tried the one remaining antibiotic the organism responds to. It triggered a life-threatening anemia.
"What are we going to do, if all these medicines run out?" he asks. "It's scary, when you have a family and you've come this far. In the back of your mind, it can get you."
The possible collapse of Brown's treatment could be avoided, if there were another option. Right now, there are no new antibiotics that doctors can add to his regimen. In the US, antibiotic innovation has skidded to a halt. The last novel class approved by the FDA debuted in 1984.
A piece of legislation lined up for a vote in Congress, called the Pasteur Act (named both for the 19th-century microbiologist and to stand for Pioneering Antimicrobial Subscriptions to End Upsurging Resistance), could repopulate that empty landscape by guaranteeing government funds to help a small number of new antibiotics make it to market. The proposal has bipartisan support in both the House and Senate, is backed by the Department of Health and Human Services (HHS), was implicitly endorsed in the last White House budget, and resembles programs already implemented in other countries.
Independent analysts and drug-company personnel all say the measure is critically needed. But the Congress that reconvenes this week will be bruised from vituperative electioneering and distracted by races that remain unresolved. The body will also have to make decisions on a raft of legislative proposals that were delayed earlier in the year by hyperpartisan jostling, and will have to choose what they can accomplish before their session ends around Christmas Eve. If the Pasteur Act can't get through by then, it will need to be reintroduced when the new Congress convenes in January. But that session will be focused on the 2024 election, and it could be hard for other issues to break through.
"If this doesn't pass, or something like it doesn't get implemented, then I don't know what Plan B is," says Joe Larsen, a vice president at Locus Biosciences Inc. who launched an Obama–era program of antibiotic investment while serving in the US government's Biomedical Advanced Research Development Authority. "We need to re-envision the way we support antimicrobials in the US."
That patients might run out of effective antibiotics is a jarring thought. The Centers for Disease Control and Prevention estimates that antibiotic-resistant infections already kill more than 48,000 Americans each year and sicken 2.8 million. A January study in The Lancet estimated the annual global death toll at 1.27 million. Antibiotic resistance got worse during the pandemic as health care workers tried to protect Covid patients from bacterial infections, not just in individual outbreaks in hospitals but across the US.
But for more than two decades, the household-name pharmaceutical firms that used to lead the market—Eli Lilly and Company, Bristol Myers Squibb, Wyeth, and Novartis, among others—have been backing out of antibiotic production. The underlying reason: simple math. A team of economists estimated in 2016 that it costs $1.4 billion to bring any new drug to market, including a new antibiotic. Yet antibiotics aren't taken in the volume that, say, cardiovascular drugs are, and don't command the stratospheric prices of new cancer therapies. Once they pass FDA approval, they earn money slowly. This triggers a fatal mismatch between expenditure and earnings: By one estimate, a new antibiotic has to earn $300 million a year to break even—yet industry records show that few make even $100 million a year.
Lacking enough income to balance their expenditures, the big companies left the field to small biotechs. These new players believe in the mission, but typically don't have income from other product lines to buoy them while they wait for sales. Since 2010, the makers of five out of 15 new antibiotics approved by the FDA have folded or sold themselves at auction because they could not outlast the lag between approval and earnings. A sixth company backed off an antibiotic in Phase 3 trials in May and laid off three-fourths of its staff. A seventh reorganized itself just last month.
"The market is broken," says Zachary Zimmerman, cofounder and director of the small antibiotic firm Forge Therapeutics, which currently has two new antibiotics under development. "So what we need to do is take the market out of the equation."
This is what the Pasteur Act would do. In its current form, it commits $6 billion over several years to construct a sort of subscription plan for developing new antibiotics. That dollar amount is the result of numerous compromises—when first introduced in 2020, the bill called for $11 billion—and it wouldn't all be spent on drugs. The program it would create in HHS would assemble panels of experts to evaluate whether any newly proposed antibiotic addresses an unmet need. Then they would estimate a societal value for the drug, anywhere from $750 million to $3 billion. The Treasury would disburse that money in tranches over several years. In return, the government would receive doses of the drug to dispense to federally insured patients, at no charge to them.
Compare the $6 billion in funding with the more than $1 billion cost of bringing out a single drug, and it's clear the Pasteur Act won't go far. It could support a couple of new drugs before it would need to be reauthorized. But experts who have been pressing for a program like this say that it won't only guarantee the success of individual products, but will also signal to public markets and private capital that antibiotic development can be a reliable investment.
"We hear loud and clear, especially from smaller drug companies, that they view this funding mechanism as extremely valuable to the sustainability not only of the individual antibiotics that they will put forth as candidates, but to the viability of their entire company," says David Hyun, a physician and director of the Pew Charitable Trusts' antibiotic resistance project.
There are several hurdles in the way. The first is that the returning Congress doesn't have much time left. The second is that, to succeed, the Pasteur Act will have to be attached to a larger piece of legislation, at a moment when lots of sponsors are trying to get their pet proposals through. One vehicle might be an omnibus spending bill that reauthorizes health programs on the verge of expiring. Another may be the annual, bipartisan, usually nonpolitical National Defense Authorization Act. With 66 cosponsors from both parties, Pasteur seems like a natural fit.
Yet last week, a coalition of six academics and 11 organizations—including the liberal-leaning groups Public Citizen and Doctors for America—asked the legislators who oversee military authorization to keep the measure out of that end-of-year act. In a letter to Senators Jack Reed of Rhode Island and James Imhofe of Oklahoma—the Democratic chair and Republican ranking member of the Senate Armed Services Committee—the group called the Pasteur Act "a blank check to pharmaceutical manufacturers."
That objection offers a glimpse of what might spoil the Pasteur Act while it's on the brink of success: its cost. So many large companies have been excoriated for extortionate pricing that the prospect of giving any money to any drugmaker is risky. Yet while the small biotechs holding up the field may be in pharma, they're not Big Pharma: many have just a few employees, are working on their first-ever product, and aren't earning anything yet, let alone extortionate returns. "We're hearing: It's just too much. We're not prepared to spend this much," says Mary Dwight, the chief policy and advocacy officer at the Cystic Fibrosis Foundation, which has taken on the Pasteur Act as a cause. "We would really like to flip that narrative, because it's pretty clear to us that combating antimicrobial resistance is cost effective."
According to research supported by the CDC, the US already spends $4.6 billion each year to respond to antibiotic-resistant infections. If that spending could be obviated, it would save in one year most of what the Pasteur Act would spend over several.
"If Pasteur passes, it would help not just CF patients, but the whole population," Brown says. "We got through Covid, but if there are not more antibiotics to help treat bacterial infections, then Covid is going to look like the least of our worries. If a superbug gets out and nobody has anything to work with, then we're all going to be in trouble."