PASTEUR Act re-introduced and levels up antimicrobial economics for strong innovation!

Dear All (and with thanks to Kevin Outterson for co-authoring this newsletter),

Woot, woot! Woot, woot! US Senators Michael Bennet (D-Colo.) and Todd Young (R-Ind.) and Representatives Mike Doyle (D-Pa.) and Drew Ferguson (R-Ga.) have today reintroduced the PASTEUR (Pioneering Antimicrobial Subscriptions to End Up surging Resistance) Act!

Here are the links you need:

• The text of the bill (41 pages)
• A section-by-section summary (6 pages)
• A one-page summary
• A 5-minute video from Andrew Jack at the Financial Times, a good introduction to antibiotic subscriptions like PASTEUR
• A good write up in STAT from Ed Silverman
• And a copy of the press release (found below our signatures)

As a brief review, PASTEUR was initially introduced during the last session of Congress (30 Sep 2020 newsletter) with the goal of getting feedback on the idea and generating initial support. With advice and comments taken on board, it is now being introduced in this session of Congress with the intent of getting it passed. In addition to the bicameral (Senate and House), bipartisan (Republican and Democratic) support implied by the co-sponsors, please also check the press release for statements of support from Industry, academia (Infectious Diseases Society of America), and even the UK (Thank you, Dame Sally!). We expect this to be just the beginning: already additional endorsements can be seem from groups like the Cystic Fibrosis Foundation (CF patients suffer from dangerous lung infections).

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To summarize the essence of the Act (text from the one-pager, emphasis added), PASTEUR would:

• “Form a Committee on Critical Need Antimicrobials, consisting [entirely] of representatives from relevant federal agencies, as well as [an Advisory Group of] doctors, patients, and outside experts, to develop and implement necessary guidance regarding infections of concern, and the favored characteristics [essentially, a TPP or Target Product Profile] of potential treatments.
• “Establish a Subscription Model to encourage innovative antimicrobial drug development aimed at treating drug-resistant infections. This model will be delinked, meaning that participating developers would not receive income, as a part of their subscription payments, based on volume or quantity of sales.
• “Terms & Conditions of the subscription contracts would include product availability to individuals on a government health insurance plan, supporting appropriate use, and completion of post market studies. These contracts could be valuated between $750 million and $3 billion.
• “Build on Existing Frameworks to improve appropriate use through the CDC National Healthcare Safety Network and other programs to collect and report on antibiotic use and resistance data.
• “Include Transition Measures such as smaller subscription contracts [a total of $1B is set aside for this purpose] to support novel antimicrobial drug developers that need a financial lifeline.”

Stated with a bit more detail: 

1. A Committee of federal HHS officials, with advice from an external Advisory Group, will create a scoring scheme for new antimicrobials based on favored characteristics such as novelty, spectrum, infection(s) treated, etc.  Think of this as elements of a target product profile (TPP).
   • It will take about a year after passage and establishment of the Committee for the scoring system to emerge, but we’d expect it to have features similar to those in the NHS pilot — for details on this, see our 29 Mar 2020 newsletter and search for “point system”.  The scoring system will be issued as a proposed HHS regulation, with opportunity for everyone to give comments.
2. That system will define the value that could be earned by a product and developers can request in advance an estimate of the value, as early as IND:
   • “If the Secretary approves a request, it shall publish the value of the contract that the critical need antimicrobial developer would be eligible to receive if such developer successfully demonstrates that the drug meets the maximum value of the favored characteristics listed in the application”
   • This means that sponsors will be able to raise funds for clinical trials with a clear view of the commercial value of the product to the US government. The designation derisks the commercial risks, leaving the company to deliver on the technical/scientific front.
3. The potential value of any given contract is $750m to $1b over 10 years.
4. $11b is set aside for PASTEUR. $1b of this can be used during a transitional period “… while the Secretary finalizes the subscription contract regulations.” $500M is set aside to strengthen stewardship, especially in rural, tribal, and safety-net hospitals.
5. Under this subscription, the federal government has prepaid for all of the drug needed by all US federal programs, but not private insurance in the US or any international sales. The bill encourages other governments and payers to design their own subscriptions.
6. If the drug turns out to be a dud or becomes a blockbuster, the subscriptions cease. 

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Wow! When PASTEUR passes, we’ll have all the pieces in place to drive a credible and functional AMR R&D ecosystem: the early R&D push incentives (CARB-X, Novo REPAIR, and multiple government level sources), a substantial late R&D push incentive (AMR Action Fund), and now substantial pull incentives with PASTEUR and the NHS Pilot.

The AMR R&D community has been working towards this for 10 years: the PASTEUR ACT levels the economic playing field so that it makes as much sense to pursue a new antimicrobial agent as it does to pursue a new cancer therapy. And this leveling up will only be improved as we (hopefully) see other governments jump into provide their fair share. The UK’s implied estimate of $4b as the value of truly innovative new agent has set the bar at an appropriate level and PASTEUR is saying the US will contribute its G20-proportionate share as well.

But (and this is a key point for the R&D community!), these sums of money will only be made available to products that really shine in some obvious, readily demonstrable way.

“Yet another” won’t cut it … everybody doing antimicrobial R&D needs to take a deep breath and ask if the world will be excited by what they are developing! On the theme of avoiding products that provoke a yawn response, please review the 5 June 2021 newsletter entitled “G7 Health Ministers 3-4 June Communique / Implications For Choosing Wisely.” Please also consider the ways that the various pipeline reviews have evaluated novelty and potential utility — there are some very important lessons here. 

Enough said! Let’s get busy and innovate our way out of the AMR crisis! All best wishes, John & Kevin

John H. Rex, MD | Chief Medical Officer, F2G Ltd. | Operating Partner, Advent Life Sciences. Follow me on Twitter: @JohnRex_NewAbx. See past newsletters and subscribe for the future: https://amr.solutions/blog/. All opinions are my own.

Kevin Outterson, JD, Professor of Law, Boston University & Executive Director, CARB-X (these views are personal and do not necessarily reflect the views of CARB-X or any of its funders) @koutterson

=== COPY OF PRESS RELEASE ===
FOR IMMEDIATE RELEASE
Wednesday, June 16, 2021

CONTACTS: 
Olivia Bercow (Bennet) – 202-860-5234
Heidi Reutebuch (Young) – 202-224-5623
Matt Dinkel (Doyle) – 202-557-1285
Nadgey Louis-Charles (Ferguson) – 202-802-0078

Bennet, Young, Doyle, Ferguson Introduce PASTEUR Act to Fight Antimicrobial Resistance
Bipartisan, Bicameral Legislation Would Support Development of Innovative Antibiotics to Treat Resistant Infections and Improve Appropriate Antibiotic Use

Washington, D.C.  – Today, U.S. Senators Michael Bennet (D-Colo.) and Todd Young (R-Ind.) and Representatives Mike Doyle (D-Pa.) and Drew Ferguson (R-Ga.) reintroduced the Pioneering Antimicrobial Subscriptions to End Up surging Resistance (PASTEUR) Act to encourage innovative drug development targeting the most threatening infections, improve the appropriate use of antibiotics, and ensure domestic availability when needed.

“After witnessing the COVID-19 pandemic, it has never been more clear that we need to invest in research to prepare for the next public health crisis,” said Bennet. “Infectious disease experts are already sounding alarms, and they need resources to prepare for the threat that antimicrobial resistance infections pose. With our bipartisan PASTEUR Act, we have the chance to not only learn from the mistakes we have made up to this point, but to invest in tools to better prepare for the future.”

“Americans understand – now more than ever – that we must take every reasonable and responsible measure to prevent future public health crises. Antimicrobial resistance has become a growing crisis in recent years. Market failures have resulted in a lack of needed research and development in this field which is a threat to public health. That’s why I’m proud to reintroduce our Pioneering Antimicrobial Subscriptions to End Upsurging Resistance (PASTEUR) Act to incentivize development of new antibiotics. At the same time, the PASTEUR Act will focus on educating health care providers on how to avoid overuse or misuse of these life-saving medications in order to slow the emergence of antibiotic-resistant pathogens,” said Young.

“Tens of thousands of Americans die each year from antimicrobial-resistant infections,” said Doyle. “Infectious disease experts agree that antimicrobial resistance is an urgent public health threat that requires a comprehensive, effective solution now. The PASTEUR Act will help scientists and researchers bring better antimicrobials to market, and it will help hospitals and doctors ensure these drugs are used properly.”    

“Antimicrobial resistance is a looming public health and national security crisis that may one day be our next pandemic if left unaddressed,” said Ferguson. “Applying the lessons learned from COVID by investing in pandemic preparedness now will save lives later, which is why I am so proud to be a part of this bipartisan, bicameral effort. We must bring together the unique capabilities and resources of the public and private sectors to solve the market failures impeding the development of new lines of antibiotics. The PASTEUR Act accomplishes this and I look forward to working with my partners on this legislation towards its enactment.”

According to the Centers for Disease Control and Prevention’s (CDC) Antibiotic Resistance Threats in the United States report, more than 2.8 million antibiotic-resistant infections occur in the United States each year, and at least 35,000 people die as a result. In March 2015, the U.S. National Action Plan for Combating Antibiotic-Resistant Bacteria directed federal agencies to accelerate a coordinated, full government response to antibiotic resistance and take action to expand the ability of our health care system to prevent, identify, and respond to the infection pandemic threat posed by antimicrobial resistance. Part of this plan was to increase and incent development of innovative antimicrobial drugs to treat resistant infections. Because of severe market failures in the health care system, many of the innovative antibiotic companies doing this work have filed for bankruptcy and stopped producing their critical drugs completely. 

The PASTEUR Act would address this market failure and increase public health preparedness by keeping novel antibiotics on the market and improving appropriate use across the health care system. While current contracts between the government and drug makers base payment on volume, the PASTEUR Act would establish a subscription-style model which would offer antibiotic developers an upfront payment in exchange for access to their antibiotics, encouraging innovation and ensuring our health care system is prepared to treat resistant infections. 

Statements of Support

“Colorado BioScience Association applauds Senator Bennet’s leadership on the PASTEUR Act,” said Jennifer Jones Paton, President and CEO of Colorado BioScience Association. “We appreciate your efforts to create new incentives for investment in this space. The proposed legislation will strengthen the development pipeline for antimicrobial products and accelerate the breakthrough work of Colorado companies focused on drug-resistant infections.”

“The global pandemic is a stark reminder that the nation must prepare for threats to public health—and we must act now on the growing threat of antibiotic resistance. Too many drug companies have already left the field, and the pipeline of new drugs is running dry. This bipartisan bill puts forth an innovative strategy to spur development, and make sure these lifesaving drugs will be available when we need them,” said David Hyun, Director, The Pew Charitable Trusts’ Antibiotic Resistance Project. 

“Antimicrobial resistance (AMR) threatens to unravel the gains of modern medicine, as lifesaving procedures including cancer chemotherapy, transplantation and other surgeries all rely upon the availability of safe and effective antibiotics.  AMR also weakens our preparedness and response to public health emergencies, as we have seen during the current pandemic with outbreaks of antibiotic resistant secondary infections in COVID-19 treatment units. The PASTEUR Act takes critical steps to address the threat AMR poses,” said Barbara Alexander, MD; President, Infectious Diseases Society of America; Professor of Medicine, Professor of Pathology, Duke University School of Medicine.

“Antibiotics are the quiet infrastructure undergirding modern medicine. For cancer patients, the second-leading cause of death is infection. The PASTEUR Act ensures that patients who win the fight against cancer don’t succumb to infections. It uses subscriptions to pay for antibiotics over a decade, based on value, not volume. It is the best solution for the AMR innovation gap, the final missing piece in the US National Action Plan on Combating Antibiotic-Resistant Bacteria, and demonstrates US leadership to keep us safe from the next pandemic,” said Kevin Outterson, Executive Director, CARB-X, Professor of Law & N. Neal Pike Scholar in Health and Disability Law – Boston University.

“The Antimicrobial Innovation Alliance has been working with Congress since 2012 on developing incentives in response to global AMR crisis, the silent pandemic. The PASTEUR Act represents the most thoughtful, balanced and meaningful mechanism to ‘pull’ through life-saving medicines for patients in need and we are eager to work for its implementation,” said Barrett Thornhill, Executive Director of the Antimicrobial Innovation Alliance.

“The PASTEUR Act will strengthen our nation’s preparedness and ability to confront multidrug resistant infections that claim at least 35,000 lives in the US annually.  Physicians and our patients need novel antibiotics and resources to support antibiotic stewardship, and the PASTEUR Act will deliver,” said Amy Beth Kressel, MD, MS, Professor of Clinical Medicine, Infectious Diseases, Indiana University School of Medicine.

“COVID-19 is showing that innovation and collaboration are necessary to strengthen global health security and prevent future crises, but COVID-19 will not be the last pandemic that the world faces. Now more than ever, the PASTEUR Act represents a global gamechanger in preparing for the silent pandemic of AMR. AMR is a shared priority for global leaders, with the G7 this month committing to ensure much-needed sustainable innovation in antimicrobial R&D. The global community welcomes the PASTEUR Act, and I applaud the US’ leadership in encouraging investment in developing sustainable, accessible and affordable treatments for patients. The bold action of the PASTEUR Act today would enable humanity to contain the global challenges of tomorrow, protecting global citizens against drug resistance and preserving modern medicine for all,” said Professor Dame Sally Davies, UK Special Envoy on Antimicrobial Resistance.

The PASTEUR Act would:

• Establish a subscription model to encourage innovative antimicrobial drug development aimed at treating drug-resistant infections. This model will be fully delinked, meaning that participating developers would not receive income, as a part of their subscription payments, based on volume or quantity of sales.  
• Subscription contracts would contain terms and conditions including product availability to individuals on a government health insurance plan, supporting appropriate use, and completion of postmarketing studies. These contracts could be valuated between $750 million and $3 billion.
• Build on existing frameworks to improve usage of the CDC National Healthcare Safety Network, the Emerging Infections Program, and other programs to collect and report on antibiotic use and resistance data.
• Include transition measures such as smaller subscription contracts to support novel antimicrobial drug developers that need a financial lifeline.