US National Action Plan for Combatting AMR: 2020-25 update!

Dear All (and with thanks to Kevin Outterson for doing the heavy lifting on this note),

As you may recall, the US National Action Plan for Combatting Antimicrobial Resistant Bacteria (US NAP CARB) was launched in 2015 on the heels of the 2013 CDC report on antimicrobial threats (link to that report) and is/was a 5-year plan for the period 2015-2020. This report was the engine behind such US Government (USG) activities as PACCARB (the Presidential Advisory Council on CARB, link), CDC’s 2019 updated list of antibiotic resistance threats (link to that report), CARB-X (69 projects funded to date!), and much, much more.

Released today, we now have an updated US NAP for the period 2020-2025 (link)! There’s a whole lot in this report and we will summarize the top-level ideas:

• The 2020-25 NAP proposes the same 5 goals as the 2015-2020 plan:
  • Goal 1: Slow the Emergence of Resistant Bacteria and Prevent the Spread of Resistant Infections 
  • Goal 2: Strengthen National One Health Surveillance Efforts to Combat Resistance  
  • Goal 3: Advance Development and Use of Rapid and Innovative Diagnostic Tests for Identification and Characterization of Resistant Bacteria
  • Goal 4: Accelerate Basic and Applied Research and Development for New Antibiotics, Other Therapeutics, and Vaccines 
  • Goal 5: Improve International Collaboration and Capacities for Antibiotic-resistance
• The key frameshift for this report is that there is a serious effort to create integrated activities across the entire USG with very specific targets in the near term.

We can’t do a deep dive on everything, so here’s a selective tour of the topics of greatest direct impact for the R&D community.

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Focusing in on Goal 3: (“Advance Development and Use of Rapid and Innovative Diagnostic Tests for Identification and Characterization of Resistant Bacteria”), we have these high-level objectives that span both bacterial and fungal pathogens:

1. Develop new and enhance existing diagnostics for both pathogen identification and susceptibility in at least 10 funded projects by 2021 (p.29).
2. Stimulate the appropriate adoption and use of diagnostics, supported by guidelines (p.30).

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Focusing in on Goal 4: (“Accelerate Basic and Applied Research and Development for New Antibiotics, Other Therapeutics, and Vaccines”), we have these high-level objects that are focused on therapeutics for bacterial infections but that also include mentions of non-traditional approaches such as “bacteriophages, monoclonal antibodies, immune modulators, and phytochemicals” (p.31) as well as vaccines for both bacterial and fungal infections. Note also the integration of goals from both agriculture and DoD:

1. Expand basic and applied interdisciplinary research with a target 1000 (!) publications by 2021.
2. Welcome attention is paid to small steps to rebuild the research workforce, calling for at least 60 new or early-career investigators by 2021 (p.31).
3. 100 new awards (including CARB-X, NIH, and BARDA awards) for pre-clinical therapeutic R&D by 2024 as well as additional candidate therapeutics from the DoD and the Department of Agriculture (p.33, Objective 2.1).
4. In clinical development, 10 clinical therapeutic candidates by 2022, with 3 NDAs for antibacterial therapeutics by 2025 (p.33, Obj. 2.2).
5. 25 preclinical programs for prevention by 2022, plus 2 for agricultural use (p.34). Along with this, there is a strong push to clarify pathways for preventatives, including vaccines (p. 34-35).
6. FDA guidance in support of the above.

Within Goal 4, the sub-objectives of “promote sustainability of the commercial market for new antibiotic products” are of great interest and are quite specific, even if they fall short of calling for additional push and especially pull incentives (as the GAO noted earlier this year, link to report). The 4 initiatives are:

1. Support the creation of a network of clinical trial sites to reduce barriers to research and to establish a comprehensive understanding of the safety and effectiveness of new antibiotic agents in challenging clinical settings and indications, to enroll patients by 2023 (p.35). (Note that this is a long-standing wish: See this prior manuscript in CID, this white paper sponsored by Wellcome Trust, and this concrete business plan developed by Wellcome Trust.)
2. Examine changes in new technology add-on payments (NTAP) under the CMS Inpatient Prospective Payment System (IPPS) Final Rules, starting with the FY 2020 IPPS/long-term care hospital prospective payment system final rule, to inform potential additional actions. (But, note that HHS passed up the chance earlier this year to make a change that would have substantially moved the needle.)
3. Strengthen commercial markets for antibiotic products through direct Public Health and National Security purchases by BARDA (p.36). This appears to call for more contracts similar to the one BARDA recently (Dec 2019) awarded to Paratek (link to press release).  
4. Support efforts to secure U.S.-based manufacturing infrastructure (p.36)

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Within Goal 5 (” Improve International Collaboration and Capacities for Antibiotic-resistance”), global leadership:

• The most surprising commitment is to appoint a “US federal champion” to be the global ambassador on this issue (p.37): Can the US find its own Dame Sally?
• Goal 5 also featured strong support for global leadership and multilateral collaboration.
  • Specific targets are included to assist 10-15 LMICs with national action plans (including WASH [Water, Sanitation, And Hygiene] capacity building) and 4 LMICs with capacity building for stewardship by 2022 (p.39).
  • Also, there is a strong emphasis on building shared surveillance capacity: e.g., “one international AR Lab Network project” (p. 40).
• Plus, we are promised a global regulatory conference to align clinical trial regulations by 2023 (p.42). Kudos to the HHS Office of Global Affairs!

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Wow! When combined with the momentum behind (i) the PASTEUR Act and its intent to create a delinked reward model (link to 30 Sep 2020 newsletter), (ii) the DISARM Act and its intent to level the playing field for use of novel inpatient antibiotics (background article by Kevin), and (iii) the CMS IPPS FY2020 Final Rule that begins to implement a way to recognize the overall cost of managing drug-resistant infections (link to 4 Aug 2019 newsletter), we are seeing a further increase in support of R&D for antibacterial agents.

Way to go on the part of our USG colleagues! How VERY exciting — the potential benefits to the global community are immense! Thank you!

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So, please go get busy and discovery something new … and if you need inspiration, please check out the 28 April 2020 newsletter (link) entitled “Movies to Discovery Antibiotics By!” A few things have been added to the online version since the newsletter was sent around!

All best wishes, Kevin & John

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  

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.