Bill that puts more antibiotics on market no sure thing

Bacteria resistant to antibiotics continue to be a problem that merits monitoring because the pathogens can possibly kick-start the next pandemic, but a bill before Congress promises to wheel new medicinal weapons into the contest.

The Pioneering Antimicrobial Subscriptions to End Upsurging Resistance (PASTEUR) Act, if passed, would create a public-private effort to create new antibacterial medications by reassuring pharmaceutical companies that there’d be a market for their product.

The legislation awaits approval by the current Congress, and some proponents worry the next Congress might not pass it. On the other hand, in a desert of hyperpolitical polarization, PASTEUR can be seen as a rare oasis of across-the-aisle cooperation.

The bill had originally been put forward in 2020 and then put forward again in June 2021 by Sen. Michael Bennet, D-Colorado; Sen. Todd Young, R-Indiana; Rep. Mike Doyle, D-Pennsylvania; and Rep. Drew Ferguson, R-Georgia. The bill mandates that the Department of Health and Human Services forge subscription contracts with pharmaceutical companies in which those companies would be assured of a market thanks to federal funding.

Neil Clancy, M.D., an infectious disease physician at the University of Pittsburgh and the VA Pittsburgh Healthcare System, told Fierce Healthcare “it is important for physicians, particularly those outside of the field of infectious disease, to understand how big a problem antimicrobial resistant bacteria and fungi are, and fragile the antibiotic development pipeline is."

"Without some changes to the current antibiotic development and reimbursement model, we run the risk of not having new antibiotics to treat emerging resistant infections in the future," Clancy said.

The bill said that “a manufacturer of a Food and Drug Administration-approved antimicrobial drug may apply to HHS to have the drug designated as a critical-need antimicrobial, and HHS may enter into a subscription contract for such a critical-need antimicrobial. The bill imposes certain requirements related to such contracts, including a mechanism to lower payments under the contract in certain instances to limit the manufacturer's revenue from the drug.” Proponents of the act refer to this as the “pull” incentive.

About 165 organizations, including the Infectious Diseases Society of America and the Pharmaceutical Research and Manufacturers of America, sent a letter (PDF) urging Congress to pass the PASTEUR Act.

The letter said that “delays in the passage of PASTEUR are delays in the development of novel antimicrobials to treat highly resistant, life-threatening infections—delays that many patients, including those particularly susceptible to infections, such as patients with cystic fibrosis, cancer, or organ transplants, cannot afford.”

Not every individual or organization in the healthcare establishment backs the passage of the act. Some experts and medical organizations sent another letter (PDF) to Congress in November in which they raise their objections.

That letter said that the act “would award billions in federal funding to pharmaceutical companies for newly developed antimicrobials as a financial incentive. However, it does not address the overarching problem that recent antimicrobials approved by the FDA have not been proven to work against resistant infections or are not more beneficial than other available and less expensive alternative treatments. Under the PASTEUR Act, taxpayer dollars will be wasted as a blank check to pharmaceutical manufacturers for antimicrobials of limited benefit.”

Clancy said that the letter against the PASTEUR Act “doesn’t reflect how antibiotic development works or how antibiotics get approved or used in the marketplace.”

The letter writers don’t acknowledge that in the real world, antibiotics that were shown to be noninferior to existing antibiotics have proven to be superior once in the clinic to what’s typically used against infections by resistant bacteria. Not everything can be measured in a clinical trial, said Clancy. A new antibiotic might be less toxic or easier to administer. Perhaps it can be given less frequently. These considerations aren’t usually taken into account when measuring the superiority of a new antibiotic.

Brad Spellberg, M.D., chief medical officer at the Los Angeles County+University of Southern California Medical Center, said he worries that the incentives offered to pharmaceutical companies in the PASTEUR Act would foist upon the market antibiotics that aren’t that much better than what’s currently available.

“We already have multibillion dollar push incentives from numerous funded sources, including NIAID, BARDA, Wellcome Trust, REPAIR Fund, AMR fund, CARB-X,” Spellberg told Fierce Healthcare in an email. “It is actually now possible for industry to literally spend not one dollar of their own R&D money to pay for all work from pre-clinical development (including lead optimization through GMP and tox to IND filing) through Phase II/III clinical trials (funded by BARDA) for new antibiotics.”

He added that the antimicrobial resistance situation is much better than it was 20 years ago and had been improving year over year up until the COVID-19 pandemic, but should again continue improving once COVID becomes endemic.

“We have a breathing period to actually make fundamental long-term sustainable changes that will last for decades and centuries, rather than throwing money at the problem for six new drugs that resistance will catch up to 10 years later anyway,” Spellberg said.

The idea of a subscription model is the one thing about PASTEUR that differentiates it from other proposed solutions, he says.

“A subscription model makes a lot of sense when you have a drug that you want people to use widely, but its uses are limited because it is so expensive,” said Spellberg. “So, it has worked well in the Hepatitis C Virus space, for example, where treatment not only benefits the individual, but limits transmission to others. You want as many people as possible on HCV therapy, but the drugs are multiple tens of thousands of dollars to prescribe, which limits health systems' abilities to prescribe them.”

Netflix, he said, is a great deal for somebody who watches a lot of programs that they’d otherwise have to pay for per episode.

“PASTEUR is a clever maneuver by industry to flip the subscription model around and get the government to pay them high amounts of money for drugs that will barely ever be used,” said Spellberg. “It’s the opposite of how subscription models have been used to date. It would be like paying monthly fees for a service no one in your family ever watches. Why keep paying? Who is the customer in this scenario? If the public and the taxpayers are the customer, this is a bad deal. If pharma is the customer, it’s a great deal.”