A bill introduced in Congress late last month has given antibiotic-development advocates renewed hope that policy makers recognize—and want to do something about—the crisis that's threatening the pipeline for new antibiotics.
Dubbed the PASTEUR (Pioneering Antimicrobial Subscriptions to End Upsurging Resistance) Act, the bill would create a subscription payment model based on the value of new antibiotics for the healthcare system, rather than on the volume of units sold.
Under this model, the federal government would award a contract, ranging from $750 million to $3 billion over a period of up to 10 years, to a company that develops a "critically needed antimicrobial." In return, patients covered by federal insurance programs would receive the drug at no cost. Drug developers and providers would also have to promote appropriate use of the drug.
If the legislation is passed, Congress would provide $11 billion over 10 years to support the program.
It's the kind of legislation that John Rex, MD, has been waiting for. Rex, a physician and drug developer with more than 30 years of experience in the antimicrobial development space, has been focusing his efforts in recent years on advancing regulatory and reimbursement policies that could help solve the broken financial model for new antibiotics. His newsletter, AMR Solutions, keeps readers up to speed on the latest policy news on antibiotic resistance, antimicrobial research and development (R&D), and stewardship.
Medical 'fire extinguishers'
CIDRAP News spoke recently with Rex about the significance of the PASTEUR Act and the AMR Action Fund, how the COVID-19 pandemic has added new urgency to efforts to boost antibiotic development, and why he calls antibiotics the "fire extinguishers of medicine."
The following excerpts from the conversation have been lightly edited for clarity.
CIDRAP News: It seems that the COVID-19 pandemic has given some momentum to efforts to develop policy-based solutions to the broken financial model for new antibiotics. Do you sense that people are taking this issue more seriously because of COVID-19?
Rex: I do think COVID-19 has helped increase understanding. If nothing else, it permits you to tell a really compelling story. The simplest version of it is, imagine that a year ago you had been a drug company with a drug for COVID-19, or for coronaviruses in general. Could you have stayed in business a year ago? The answer is no.
And yet, here today, the lack of that fire extinguisher is catastrophic for the world. Had we had that fire extinguisher, we'd have a few cases in China, and a few cases here and there before we caught on, but we would have put the fire out back in March with an appropriate therapy. So it really brings it to life. Understanding the idea of preparedness is tricky, and this gives you a real feel for why you want to prepare things in advance for infections.
Let's talk about the PASTEUR Act, a bill introduced recently by Sen. Michael Bennett (D-Colo.) and Sen. Todd Young (R-Ind.). What are your thoughts on the legislation? Does the bill address the underlying problem of the financial hurdles for antibiotic development? How so?
Rex: PASTEUR is a fantastic step forward. That's the only way I can describe it. We have been working for 10 years to articulate the why and the what of a tool that would address the fundamental disconnect around new antibiotics, and PASTEUR has done it right.
It has proposed the idea that new antibiotics would be scored on a set of targets that we would agree on, and those goals would be defined based on clear science. And it says that if you achieve these goals, you will receive a delinked reward. And that's the third element here, that the payment to the sponsor is not dependent upon on how much drug we use in human beings, it's dependent on the value of the drug as a fire extinguisher for future infections.
Here's where I have to insert this notion of antibiotics as the fire extinguisher of medicine. Infections, like fires, go quickly: once the building is on fire, it's too late to build a fire department. And PASTEUR recognizes that. And the value it has put on these fire extinguishers is in the right numerical range. It's between $750 million and $3 billion, for the United States. And what we hope is that other parts of the developed world—the rest of the G7 countries at least—will chip in.
The United Kingdom is testing a subscription-type model for antibiotics. What are your thoughts on the UK program?
The United Kingdom has already started a pilot project that is very similar to PASTEUR. It has a point scoring system, they're looking for two good drugs, they're saying it's a pilot, and they're going to build on it. PASTEUR basically has funding for about five or six drugs, and it's got a 10-year clock.
So both the United Kingdom and the United States are doing the right thing. They're laying out concrete targets that will tell the R&D world, "if you develop a drug that has these properties, that's a fire extinguisher we need, [and] we will pay you for the existence of that fire extinguisher if you bring it to market."
That's what we need. Because otherwise, new antibiotics fall flat, and that's the brutal truth. Of the last 15 antibacterials approved by the FDA [Food and Drug Administration], five of the companies or products are effectively unavailable, or in bankruptcy, or both. And these are interesting new drugs. There are circumstances where you would have liked to have had them. And they're not available.
Seeking optimal financial incentives
Is the subscription-style model a more feasible solution than market-entry rewards? Or are market-entry rewards a possible solution as well?
In effect the PASTEUR Act is a market-entry reward. If you think about it, the definition of a market-entry reward—and we've kind of gone back and forth on what that is or should look like—is it's a payment you receive when you bring a drug onto the market. And it is a payment that does not have to do with how many fires we put out.
Again, I have to go back to the fire extinguisher analogy. How do we set the fire person's salary? Do we pay them per fire? Of course not. We pay them an annual salary. And if, at the end of the year, there have been no fires, do we reduce their salary? Do we dock them? No.
Antibiotics are so different from any other drug. There's no point in paying for cancer drugs unless you're treating somebody's cancer. But with antibiotics, there's huge value in paying to have them in a pharmacy near you.
You wrote in your newsletter that the AMR Action Fund "brought tears to your eyes," but you also noted that it isn't a complete fix. So what can the AMR Action Fund achieve, and what can't it achieve?
Rex: The AMR Action Fund can do two things. First, it's money that's ready right now. And that money can be used to fund phase 2 and 3 [trials] for a handful of drugs, so that by approximately 2030, there will be two to four drugs that have come to approval. That's the goal.
At the same time, those drugs will all either fail to come to market or fail to stay on the market. They'll all fail unless things like the PASTEUR Act get done. The AMR Action Fund is an opportunity to say strongly and clearly to the global community "You can see these drugs, and you can't have them, unless you do X, and here's what X looks like."
It goes all the way back to COVID-19. Think about how differently we'd all be feeling if we had a therapy for COVID-19. We would not be anywhere near in as bad shape as we are right now.
So it is in some sense a virtuous circle. We've got people awakened to the problem, and not just the techy types, but our political leadership, our economic leadership. Why should the financiers care about this? Because it screws up the ability of healthy citizens to go do healthy citizen things that make our economy go. It wreaks havoc with everything.
If we don't see action on the policy front to address the broken financial model for antibiotics, are we going to see more bankruptcies like with Achaogen and Melinta in the coming years?
Rex: That's easy. Yes. We will see more compounds fail—compounds that you would like to have that will fail. And they will fail because we don't pay for them in a fashion that compensates for their medical utility.
I should come back to PASTEUR, because something else that PASTEUR does right [is that] it recognizes stewardship and it has explicit calls for how that would be woven in as well. And that's the cool thing about the de-linked [reimbursement] model: It actually takes stewardship and the value of the new drug and brings them together so that everyone can say, "I want to do both of those things."
I'd like to talk about the origins of the idea of antibiotics as the fire extinguisher of medicine. Explain more about what you mean by that, and why is that a useful way to look at antibiotics?
Rex: Kevin Outterson [executive director of CARB-X] and I were standing in Oslo at a DRIVE-AB meeting talking about antibiotics and how to convey this concept of "you need them, but you don't want to use them." I remember standing in the hallway with him, and the words "they're like fire extinguishers" came out of my mouth.
Kevin and I had actually started off with the idea of battleships—but that was too militaristic. So we were batting around ways to get there, and Kevin and I kind of forced those words into the air, and suddenly we had this really useful meme.
Why is it helpful? Because the parallels are so strong. Infections go really quickly. Fires go really quickly. You have smoke detectors for fires; you have microbiologists for infections. You have antibiotics that can be used to put out the infection, just as fire extinguishers can be used to put out the fire.
The whole idea of preparedness is hard to explain, but antibiotics as fire extinguishers, people get that. It's just turned out to be a really vivid metaphor.
What do you hope to see 10 years from now? If we look to 2030, if you are optimistic, what does the antibiotic development, antibiotic payment landscape look like?
Rex: The PASTEUR Act and its equivalents in other countries around the world are clearly established, so much so that starting a development program for an anti-infective makes as much financial sense as starting a program for Alzheimer's, or cancer, or anything else. That's the big goal.
