Kevin Outterson – AMR.Solutions https://traf-x.amr.solutions Antimicrobial Resistance Solutions with Dr. John H. Rex Tue, 17 Feb 2026 09:07:30 +0000 en-US hourly 1 https://traf-x.amr.solutions/wp-content/uploads/2022/04/Fire-Extinguisher-icon-70x70.png Kevin Outterson – AMR.Solutions https://traf-x.amr.solutions 32 32 UK Subscription model goes live! Value bands cover entire UK! https://traf-x.amr.solutions/2024/08/19/uk-subscription-model-goes-live-value-bands-cover-entire-uk/ Mon, 19 Aug 2024 14:52:44 +0000 https://amr.solutions/?p=16775

Dear All (with thanks to Kevin for leading on this newsletter and with a wonkish / long-read alert on this email … settle in for the ride!),

Great news from TEAM UK! As of 12 August, the UK Subscription Program is no longer a pilot but is fully operational with an initial application deadline of 12 Sep 2024. Here are the links you need to follow along:

There’s a fair bit to digest if you are going apply, but the key points that everyone needs to know are briefly summarized here with extended details below our signatures:

  1. The subscription process now covers the entire UK (England, Scotland, Wales, and Northern Ireland) and with this the value bands are higher.
  2. The payments can be made for up to 16 years, until the UK exclusivity expires (including patents, SPCs, or regulatory data protection).
  3. The Clinical Technical Evaluation has been thoughtfully updated, giving best-in-world clarity on what will qualify for an antibacterial pull incentive.
  4. Eligible products include existing and upcoming products.
  5. This year’s tender has an application deadline of 12 Sep 2024.
  6. And a few constructive critiques
    1. The financial stability criteria should better consider both the circumstances and importance of small companies in providing critical antibiotics
    2. Provisions are needed regarding global stewardship and access
    3. Provision are needed for increasing value with label expansion [see addendum, below]

27 Aug 2024 addendum: Per a discussion with staff at NICE, products could be moved to a higher (or lower) band if new evidence emerges. The sponsor could submit new efficacy data at/after 3 years in the subscription model; NICE could trigger a review sooner if safety issues arise.

Woot, woot! Wow! Our critiques not withstanding, it is marvelous to see this process become business as usual! MANY THANKS TO TEAM UK for their WORLD-LEADING WORK on Pull Incentives!

It truly is the case that we’ve pushed as hard as we can and and now we need to start pulling via the PASTEUR Act in the US, the different (and potentially complementary) proposals of pull incentives from the European Commission, as well as the ideas/pilots from Japan, Canada, Italy, and Switzerland.

Onward! All best wishes, Kevin and 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.

EXTENDED DETAILS, POINT-BY-POINT
1. The subscription process now covers the entire UK (England, Scotland, Wales, and Northern Ireland) and with this the value bands are higher:

As you can see, the highest possible value is GBP 23.7m ($30.6m at current exchange rates). As the total budget allocated for the entire program is up to £100 million per year, the UK is certainly paying its “fair share” for antibacterial innovation (see also our 2023 article on “fair share”). 

2. The payments can be made for up to 16 years, until the UK exclusivity expires (including patents, SPCs, or regulatory data protection).

3. The Clinical Technical Evaluation has been thoughtfully updated, giving best-in-world clarity on what will qualify for an antibacterial pull incentive. The details are found in Document 6 (“Clinical_Technical_Evaluation criteria”) and we highlight 2 key elements:

3.a. The Product will be scored against the criteria below, with the weights shown below. The criteria are in 3 groups: (1A-D) Relative effectiveness and unmet clinical need (45%) of the overall value, (2A-F) pharmacological benefit (25%), and (3A-G) Health system benefit (30%):

3.b. Each of these factors is explained in the text of Document 6, including the types of evidence that will be accepted. For example, the extended rules for Criteria 1A show how the awarded points follow the WHO Priority Bacterial Pathogen List to vary by pathogen (and these rules also make clear the focus on bacterial pathogens; the pathogens from the fungal PPL are not in scope for this tender): 

The technical criteria in document 6 are required reading for anyone developing an antibiotic which might want a UK subscription.

4. Eligible products include existing and upcoming products. Here are the eligibility rules:

  • “an antimicrobial with a license for the UK and a UK launch where the marketing authorisation has already been granted or is likely to be granted before 31 July 2025 and
    • “the Licensed Indication(s) include one or more pathogens on the WHO critical priority pathogen list 2024 against which the antimicrobial is active.
  • “The product should also be within the period of the exclusivity defined either by the patent, supplementary protection certificate or regulatory data protection and
    • “have a minimum remaining twelve (12) months before the date of loss of exclusivity from the date of commencement of the contract”


5. Don’t miss the bus! The application timeline for the next round of subscriptions is very short: 12 September (one month from publication, see time table below). The expectation is that the tender will be repeated annually with the proviso that its terms might be updated (from the long read webpage, we have this: “The documentation will include the eligibility and the award criteria. These will be reviewed each year before notice of the tender is given.”)

CONSTRUCTIVE CRITIQUES, POINT-BY-POINT

  1. We would like to see the UK modify Document 3, “Guide for assessing financial standing.” 
    1. In a normal procurement process, governments want to ensure that the counterparty is financially sound.
      1. For antibiotics, especially in small companies, pull incentives like the Subscription are also designed to rescue financially struggling companies. It make little sense to apply the standard financial scoring methodology to small antibacterial biotechs.
      2. It would be akin to requiring proof of financial solvency prior to receiving disaster assistance after a storm.
      3. This issue was raised in the comment process on the program: In the pilot stage of the Subscriptions, some small company applicants found this to be a formidable barrier.
      4. This might force small companies to partner with larger, more solvent, companies in order to apply to UK. That might be a good thing, but the decision should be made on business grounds, not the standard language of a procurement agreement.
    2. Further, the company gets a lower score if this contract is a substantial portion of their global revenue and if they have a bad D&B score.
      1. Rather than this, we think that we want small companies with no other revenue yet to apply to G7 pull incentives. They need 22 points to pass this financial check.
      2. We want to hear from any small companies who have a product UK might want, but who miss this pass/fail financial hurdle.
  2. We would like to see provisions added regarding global stewardship & access.
    1. The UK has a clear opportunity to lead here by imposing reasonable contractual conditions that support global stewardship and access.
    2. Shionogi’s license of cefiderocol to GARDP is a good model for this (25 Sep 2023 newsletter).
    3. This would be a great opportunity to reinforce the ideas from the Stewardship & Access Guide created by CARB-X, Wellcome, and partners (22 March 2021 newsletter).
  3. No provisions were found allowing the selected drug to be rescored upward after a label expansion or other evidence of greater clinical utility.
    1. We would like to see processes that support label expansions.

Current funding opportunities

  • The GHIT Fund has announced its 21st Request for Proposals for its Hit-to-Lead Platform to support drug discovery and development process to address Malaria, Tuberculosis, Chagas disease, and Visceral leishmaniasis. Go here for the RFP: GHIT-RFP-HTLP-2024-002. The deadline is 30 Aug 2024.
  • The AMR Industry Alliance have announced the 2024 edition of their ongoing annual series of stewardship prizes. Applications for innovative approaches to AMR stewardship are sought from public, private or not-for-profit health care organization or institution operating in an LMIC. This year’s deadline is 1 Sep 2024. Go here for details.
  • ENABLE-2 has continuously open calls for both its Hit-to-Lead program as well as its Hit Identification/Validation incubator. Applicants must be academics and non-profits in Europe due to restrictions from the funders. Applications are evaluated in cycles … see the website for details on current timing for reviews. 
  • CARB-X has open calls at intervals that span four areas: (i) Therapeutics for Gram-Negatives, (ii) Prevention for Invasive Disease, (iii) Diagnostics for Neonatal Sepsis, and (iv) Proof-Of-Concept for Diagnosing Lower-Respiratory-Tract Infections. See this 6 Mar 2024 newsletter for a discussion of the call and go here for the CARB-X webpage on the call. There are multiple opportunities to submit — see the CARB-X webpage for details.
  • BARDA’s long-running BAA (Broad Agency Announcement) for medical countermeasures (MCMs) for chemical, biological, radiological, and nuclear (CBRN) threats, pandemic influenza, and emerging infectious diseases is now BAA-23-100-SOL-00004 and offers support for both antibacterial and antifungal agents (as well as antivirals, antitoxins, diagnostics, and more). Note especially these Areas of Interest: Area 3.1 (MDR Bacteria and Biothreat Pathogens), Area 3.2 (MDR Fungal Infections), and Area 7.2 (Antibiotic Resistance Diagnostics for Priority Bacterial Pathogens). Although prior BAAs used a rolling cycle of 4 deadlines/year, the updated BAA released 26 Sep 2023 has a 5-year application period that ends 25 Sep 2028 and is open to applicants regardless of location: BARDA seeks the best science from anywhere in the world! See also this newsletter for further comments on the BAA and its areas of interest.
  • HERA Invest was launched August 2023 with €100 million to support innovative EU-based SMEs in the early and late phases of clinical trials. Part of the InvestEU program supporting sustainable investment, innovation, and job creation in Europe, HERA Invest is open for application to companies developing medical countermeasures that address one of the following cross-border health threats: (i) Pathogens with pandemic or epidemic potential, (ii) Chemical, biological, radiological and nuclear (CBRN) threats originating from accidental or deliberate release, and (iii) Antimicrobial resistance (AMR). Non-dilutive venture loans covering up to 50% of investment costs are available. A closing date is not posted insofar as I can see — applications are accepted on a rolling basis; go here for more details.
  • The AMR Action Fund is open on an ongoing basis to proposals for funding of Phase 2 / Phase 3 antibacterial therapeutics. Per its charter, the fund prioritizes investment in treatments that address a pathogen prioritized by the WHO, the CDC and/or other public health entities that: (i) are novel (e.g., absence of known cross-resistance, novel targets, new chemical classes, or new mechanisms of action); and/or (ii) have significant differentiated clinical utility (e.g., differentiated innovation that provides clinical value versus standard of care to prescribers and patients, such as safety/tolerability, oral formulation, different spectrum of activity); and (iii) reduce patient mortality. It is also expected that such agents would have the potential to strongly address the likely requirements for delinked Pull incentives such as the UK (NHS England) subscription pilot and the PASTEUR Act in the US. Submit queries to contact@amractionfund.com.
  • INCATE (Incubator for Antibacterial Therapies in Europe) is an early-stage funding vehicle supporting innovation vs. drug-resistant bacterial infections. The fund provides advice, community, and non-dilutive funding (€10k in Stage I and up to €250k in Stage II) to support early-stage ventures in creating the evidence and building the team needed to get next-level funding. Details and contacts on their website (https://www.incate.net/).
  • These things aren’t sources of funds but would help you develop funding applications
    • AiCuris’ AiCubator offers incubator support to very early stage projects. Read more about it here.
    • The Global AMR R&D Hub’s dynamic dashboard (link) summarizes the global clinical development pipeline, incentives for AMR R&D, and investors/investments in AMR R&D.
    • Diagnostic developers would find valuable guidance in this 6-part series on in vitro diagnostic (IVD) development. Sponsored by CARB-X, C-CAMP, and FIND, it pulls together real-life insights into a succinct set of tutorials.
  • In addition to the lists provided by the Global AMR R&D Hub, you might also be interested in my most current lists of R&D incentives (link) and priority pathogens (link).

John’s Top Recurring Meetings
Virtual meetings are easy to attend, but regular attendance at annual in-person events is the key to building your network and gaining deeper insight. My personal favorites for such in-person meetings are below. Of particular value for developers are the AMR Conference and the ASM-ESCMID conference. Hope to see you there!

  • 17-20 Sep 2024 (Porto, Portugal): ASM/ESCMID Joint Conference on Drug Development to Meet the Challenge of Antimicrobial Resistance. Go here to register!
  • 16-20 Oct 2024 (Los Angeles, USA): IDWeek 2024, the annual meeting of the Infectious Diseases Society of America. Go here for details.
  • 25-26 February 2025 (Basel, Switzerland): The 9th AMR Conference 2025. Go here to register! 
  • 11-15 April 2025 (Vienna, Austria): ESCMID Global 2025, the annual meeting of the European Society for Clinical Microbiology and Infectious Diseases. Go here for details. 

  Upcoming meetings of interest to the AMR community:

  • [HAS HAPPENED; NOTEWORTHY VIDEO]: 22-23 May 2024 meeting of PACCARB. If you were intrigued by the 23 July 2024 newsletter entitled “Conflict-Borne XDR Superbugs”, you should note that PACCARB devoted its 23 May 2024 morning session to the topic of combat-related drug resistance. See page 3 of the agenda and then follow along in the video on YouTube.
  • 22 Aug 2024 (virtual, 11a-12.30p EDT, 5p-630p CEST): GARDP REVIVE Webinar entitled “Exploring non-traditional antimicrobials: Insights from three cases.” Go here for details and to register. If non-traditional approaches interest you, please do be sure to review the challenges that are raised in the papers discussed in the 6 Aug 2019 newsletter entitled “Non-Traditional Antibiotics: A Pipeline Review And An Analysis Of Key Development Challenges.” Developing non-traditional products is MUCH harder than you might expect … it is important to know the issues!
  • [NEW – DON’T MISS IT] 28 Aug to 28 Sep (Off-Broadway, New York City, the Alice Griffin Jewel Box Theatre): Lifeline, the musical story of Sir Alexander Fleming’s discovery of penicillin. Previously entitled The Mould that Changed the World, the musical is a two-time Edinburgh Festival Fringe sell-out (2018 and 2022) and has toured to London, Glasgow, Atlanta and Washington DC (2022). This 5-week run in NYC is timed to be in support of the High-Level Meeting on AMR (HLM AMR) during UNGA 2024. Go here for a blurb and here to book your tickets!
  • [NEW – DON’T MISS IT] 9 Sep 2024 (9a-4p ET, in-person or virtual): FDA have announced an AMDAC (Antimicrobial Drugs Advisory Committee) meeting that will discuss “new drug application 213972, for oral sulopenem etzadroxil/probenecid tablets consisting of 500 milligrams (mg) sulopenem etzadroxil and 500 mg probenecid, submitted by Iterum Therapeutics US Ltd., for the proposed indication of treatment of uncomplicated urinary tract infections caused by designated susceptible bacteria in adult women 18 years of age and older.” Try to make time to listen to this … every FDA Advisory Committee is a master class in regulatory thinking! Go here for the Federal Register notice and here for the meeting’s webpage: materials are typically posted 2 days before the meeting. 
  • 17-20 Sep 2024 (Porto, Portugal): ASM/ESCMID Joint Conference on Drug Development to Meet the Challenge of Antimicrobial Resistance. See Recurring Meetings list, above.
  • [NEW] 24 Sep 2024 (in person, 7.45-10a ET, New York City): Breakfast meeting entitled “Advancing Together: Securing the Global AMR Agenda by Harnessing the Collective Strength of Multi-Sector Partnerships”, sponsored by bioMèrieux, The Wellcome Trust, The American Society of Microbiology, and the Republic of Malawi. This occurs two days before the 26 Sep 2024 UNGA HLM on AMR. Go here to register.
  • 16-20 Oct 2024 (Los Angeles, USA): IDWeek 2024, the annual meeting of the Infectious Diseases Society of America. See Recurring Meetings list, above. 
  • [NEW] 16 Oct 2024 (virtual and in-person, 10a-1p ET): FDA’s Rare Disease Innovation Hub, in collaboration with the Reagan-Udall Foundation will discuss how the recently announced Rare Disease Innovation Hub can engage and prioritize its work. This may seem somewhat remote, but could this have implications for rare infections? Hmm! Attend if you can! Go here for the meeting’s webpage.
  • 19-27 Oct 2024 (Annecy, France, residential in-person program): ICARe (Interdisciplinary Course on Antibiotics and Resistance). Now in its 8th year, Patrice Courvalin directs the program with the support of an all-star scientific committee and faculty. The resulting soup-to-nuts training covers all aspects of antimicrobials, is very intense, and routinely gets rave reviews! Seating is limited, so mark your calendars now if you are interested. Applications open in March 2024 — go here for more details.
  • 4-5 Dec 2024 (in person, Washington, DC): “Fungal Dx 2024: Fungal Diagnostics in Clinical Practice” is a 2-day in-person workshop organized by ISHAM‘s Fungal Diagnostics Working Group. The program and registration links are available at https://fungaldx.com/; the agenda is comprehensive and features an all-star global list of speakers.
  • 11-15 April 2025 (Vienna, Austria): ESCMID Global 2025, the annual meeting of the European Society for Clinical Microbiology and Infectious Diseases. See Recurring Meetings list, above.
]]> Impact of PASTEUR: 9.9m lives saved, ROI of 125:1 https://traf-x.amr.solutions/2022/11/29/impact-of-pasteur-9-9m-lives-saved-roi-of-1251/ Tue, 29 Nov 2022 14:43:30 +0000 https://13.43.35.2/?p=8751

Dear All (and with thanks to Kevin Outterson for being lead author on this newsletter),

(wonkish alert on this one … refresh your coffee and dig in!) Bonnifield and Towse of the Center for Global Development have released a blog post and a paper estimating the potential impact of the PASTEUR Act. Here’s what you need:

You’ll need to read the paper itself (set aside at least an hour for this … the thinking goes quite deep), but the essential point is that the authors have estimated PASTEUR’s value to the US (and the world) in terms both of lives saved and financial benefit:cost ratio should PASTEUR provide the global foundation for a Pull award to 18 new qualifying antibiotics over 30 years (that’s just 6 new drugs qualifying for PASTEUR per decade).

The results are astonishing: The US alone sees 383k lives saved and an ROI of 28:1. For the globe, lives saved total 9.9m with an  ROI of 125:1 over 30 years! The methods used are discussed in more detail below our signatures, but the strength of this approach lies in its simplicity:

  1. The value of new qualifying antibiotics is built from years of life saved.
  2. The cost of the Pull award to the US government assumes an average award of $2.1b over 10 years to 6 qualifying new antibiotics per decade.
  3. The US contribution is assumed to be 46% of a global system of Pull awards (46% is the US share of G7+EU GDP).
  4. The math includes adjustments for inflation and discounting.

The top-line results are presented first for the domestic US economy (Table 1) and then for the global economy (Table 2):

DALY = Disability-Adjusted Life Years; DALYs are assumed to convert 1:1 to QALYs (Quality-Adjusted Life Years); QALYs are assumed to have a value of $100k/year.


Yes … that’s an ROI of 28:1 for the US and 125:1 globally with 9.9 million lives saved over 30 years! Astounding!

And importantly, the US ROI remains robust at 13:1 even if the the US shoulders the entire burden by providing 100% of the Pull (see the estimates labeled “Free Rider” in the 2nd line of Table 3, below; lives saved do not change):


These results are especially striking in that the model was built using a very simple approach that is different from prior pull incentive estimates. In particular, STEDI values were not used (for a refresher on STEDI, see this newsletter or this YouTube explainer). 

Conservatively, the global health calculations also did not include additional benefits from saving health care costs as these data were not reliable on a global level. Productivity gains were also excluded, both domestically and globally, even though the World Bank found them to be substantial in their 2016 report..

Impressively, the core analysis demonstrated such high levels of cost-effectiveness from saving lives that there was no need to resort to secondary benefits.

This is as close to a slam dunk economic analysis as you will ever see. Their analysis is also congruent with the STEDI-based analyses used in the UK’s pilot showing that the high social value of antibiotics is evident even with very conservative estimates. Given their impressive social value, the funding proposed in the PASTEUR Act for compelling new antibiotics is truly a bargain.

—
The report also gives a clear account for why we have a market failure. These 8 key issues summarized on pp.4-6 of the report should be required reading for anyone trying to understand and fix the problem of AMR. Here’s their list along with our commentary:

  1. Initial sales volumes are low. Comment: Good stewardship makes this so; stewardship is great for public health but deadly for R&D companies.)
  2. Most social value is after patent expiry (Comment: This makes it difficult for a company to be appropriately rewarded during the patent period.)
  3. Clinical value is difficult to demonstrate (Comment: This surprises many when they first encounter the problem; for details, see previous newsletters on 19 Sep 2020 and 30 June 2020.)
  4. Traditional reimbursement approaches undervalue new antimicrobials (Comment: See discussions of the STEDI values (aka, the “fire extinguisher” values) of antibiotics in this newsletter and this YouTube video.) 
  5. Common hospital payment mechanisms disincentivize use of novel (more expensive) antimicrobials (Comment: This is an unanticipated impact from the 1983 reforms that bundled hospital reimbursements in Medicare. The DISARM Act would address this issue.)
  6. Point of care diagnostic tests are not being used to reduce drug resistance (Comment: Like unhappy families in Tolstoy’s Anna Karenina, each market failure in AMR is broken in unique ways. For diagnostics, we await the release of the recent US National Academies of Science, Engineering, & Medicine report.)
  7. The science is difficult (Comment: This is undoubtedly true, but the experience of CARB-X suggests that the innovation teams around the world can overcome the scientific challenges if the economics were turned around.)
  8. Regulatory approval processes for new antimicrobials are time-consuming (Comment: While antibiotics might have been at some unique regulatory disadvantage in times past, this is no longer a top-tier reason for why antimicrobial innovation is harder than other drug classes. Regulators will continue to work, but we should celebrate progress to date.)


—
Wow … what a timely and impressive paper! The authors (Towse and Silverman) as well as their funders (Schmidt Futures and Founders Pledge) are indeed to be thanked for this valuable new contribution to the economic arguments in support of delinked Pull awards such as that proposed by the PASTEUR Act. Now let’s just get it passed! Have you written to your Members of Congressx?

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.

Brief summary of the methodology

  1. The annual rate of AMR-attributable deaths was taken from the GRAM project report published earlier this year
  2. Conservatively, they focused on attributable deaths from the 6 leading pathogens causing 79% of these deaths (E. coli, S. aureus, K. pneumoniae, S. pneumoniae, A. baumannii, and P. aeruginosa)
  3. They estimate lost DALYs (disability-adjusted life years) from these deaths using data from the GRAM report.
  4. DALYs are assumed to convert 1:1 to QALYs (quality-adjusted life years) and QALYS are valued at $100k/QALY.
  5. They assume that 18 new qualifying antibiotics are needed over 30 years for for these 6 pathogens (3 new drugs/pathogen) and that:
    • The 18 new qualifying antibiotics appear steadily over that 30 years
    • Each new drug is held completely in reserve for its first 4 years
    • Each new drug reduces deaths/year by 5% from year 5 onward
    • From year 6, each new drug loses effectiveness 2% year-on-year due to emergence of resistance
    • Note that the focus on just the top 6 pathogens conservatively leaves a bit of room in the math for new qualifying drugs to cover more bugs
  6. They assume the Pull Award will provide (on average) a 10-year fully delinked award equal to the $4.2b central “best guess” required value that was estimated in Outterson 2021 “Estimating The Appropriate Size Of Global Pull Incentives For Antibacterial Medicines” (https://www.healthaffairs.org/doi/abs/10.1377/hlthaff.2021.00688).
    • They adjust the numbers for inflation
    • They use the same average value for all antibiotics that earn an award but they explicitly note that the actual reward size would need to be adjusted to reflect the merits of each qualifying antibiotic.
    • Implicit in this discussion of antibiotic value is that antibiotics not providing interesting new coverage of the target pathogens would have zero value, again consistent with the notion that not all drugs would receive a Pull award.
  7. The US fair share of this amount is 46% based on proportion of GDP within the G7 + EU.
    • This equates to $2.1b per drug from the US, a value that is roughly at the mid-point of the $750m to $3b range proposed as part of PASTEUR.

Current funding opportunities (most current list is here)

  • FDA have announced five RFPs spanning antifungal animal models, usability of antimicrobial drug labeling, urine PK-PD, and interpretive breakpoints. Applications are due dates of 23 Jan 2023 — see this newsletter for more details.
  • Current funding rounds from CARB-X are as described in this newsletter!
  • The AMR Action Fund is now open to proposals for funding of Phase 2 / Phase 3 antibacterial therapeutics. Per its charter, the fund prioritizes investment in treatments that address a pathogen prioritized by the WHO, the CDC and/or other public health entities that: (i) are novel (e.g., absence of known cross-resistance, novel targets, new chemical classes, or new mechanisms of action); and/or (ii) have significant differentiated clinical utility (e.g., differentiated innovation that provides clinical value versus standard of care to prescribers and patients, such as safety/tolerability, oral formulation, different spectrum of activity); and (iii) reduce patient mortality. It is also expected that such agents would have the potential to strongly address the likely requirements for delinked Pull incentives such as the UK (NHS England) subscription pilot and the PASTEUR Act in the US. Submit queries to contact@amractionfund.com.
  • BARDA’s long-running BAA-18-100-SOL-00003 offers support for both antibacterial and antifungal agents. This BAA has offered 4 deadlines/year since 2018 … check the most current amendment for details.
  • INCATE (Incubator for Antibacterial Therapies in Europe) is an early-stage funding vehicle supporting innovation vs. drug-resistant bacterial infections. The fund provides advice, community, and non-dilutive funding (€10k in Stage I and up to €250k in Stage II) to support early-stage ventures in creating the evidence and building the team needed to get next-level funding. Details and contacts on their website (https://www.incate.net/).
  • It’s not a funder, but AiCuris’ AiCubator offers incubator support to very early stage projects. Read more about it here.
  • The Global AMR R&D Hub’s dynamic dashboard (link) summarizes the global clinical development pipeline, incentives for AMR R&D, and investors/investments in AMR R&D.
  • In addition to the lists provided by the Global AMR R&D Hub, you might also be interested in my most current lists of R&D incentives (link) and priority pathogens (link).


Upcoming meetings of interest to the AMR community (most current list is here):

  • 27-30 Nov 2022 (Perth, Australia): 32nd International Congress of Antimicrobial Chemotherapy is the biennial congress of the International Society of Antimicrobial Chemotherapy (ISAC). Go here for details.
  • [NEW] 2 Dec 2022 (Harvard, Boston, 9a-6p with reception to follow): BAARN, the Boston Area Antimicrobial Resistance Network. A full day of networking and lectures, including a keynote by Gerry Wright. Go here for details and here to register.
  • 3-7 Dec 2022 (Banff, Canada): Novel Approaches Against Emerging Antimicrobial Resistance by Keystone Symposia. Go here for details. 
  • [NEW] 1-2 Feb 2023 (virtual): Antimicrobial Chemotherapy Conference by GARDP and BSAC in collaboration with ReAct Africa and Africa CDC. Go here for details.
  • 14 Apr 2023 (Copenhagen, Denmark; 3-6.30p CEST): ECCMID and the Global Leaders Group on AMR will jointly sponsor a symposium entitled “Forging partnerships between science and policy in Antimicrobial Resistance (AMR).” Go here to register.
  • 15-18 Apr 2023 (Copenhagen, Denmark): 33rd ECCMID. Go here for details and to register.
  • 8-12 May 2023 (Lisbon, Portugal): 41st Annual Meeting of the European Society for Paediatric Infectious Diseases. Go here for details.
  • [NEW] 14-22 Oct 2023 (residential, Annecy, France): ICARe, the Interdisciplinary Course on Antibiotics and Resistance. Now in its 7th year, this course is a deep-dive into the world of antibiotic development. Intense, rigorous, and HIGHLY recommended. Seats are always limited … apply sooner rather than later! Go here for details.

Dear All (and with thanks to Kevin Outterson for being lead author on this newsletter),

(wonkish alert on this one … refresh your coffee and dig in!) The Center for Global Development have released a blog post and a paper estimating the potential impact of the PASTEUR Act. Here’s what you need:

You’ll need to read the paper itself (set aside at least an hour for this … the thinking goes quite deep), but the essential point is that the authors have estimated PASTEUR’s value to the US (and the world) in terms both of lives saved and financial benefit:cost ratio should PASTEUR provide the global foundation for a Pull award to 18 new qualifying antibiotics over 30 years (that’s just 6 new drugs qualifying for PASTEUR per decade).

The results are astonishing: The US alone sees 383k lives saved and an ROI of 28:1. For the globe, lives saved total 9.9m with an  ROI of 125:1 over 30 years! The methods used are discussed in more detail below our signatures, but the strength of this approach lies in its simplicity:

  1. The value of new qualifying antibiotics is built from years of life saved.
  2. The cost of the Pull award to the US government assumes an average award of $2.1b over 10 years to 6 qualifying new antibiotics per decade.
  3. The US contribution is assumed to be 46% of a global system of Pull awards (46% is the US share of G7+EU GDP).
  4. The math includes adjustments for inflation and discounting.

The top-line results are presented first for the domestic US economy (Table 1) and then for the global economy (Table 2):

DALY = Disability-Adjusted Life Years; DALYs are assumed to convert 1:1 to QALYs (Quality-Adjusted Life Years); QALYs are assumed to have a value of $100k/year.


Yes … that’s an ROI of 28:1 for the US and 125:1 globally with 9.9 million lives saved over 30 years! Astounding!

And importantly, the US ROI remains robust at 13:1 even if the the US shoulders the entire burden by providing 100% of the Pull (see the estimates labeled “Free Rider” in the 2nd line of Table 3, below; lives saved do not change):


These results are especially striking in that the model was built using a very simple approach that is different from prior pull incentive estimates. In particular, STEDI values were not used (for a refresher on STEDI, see this newsletter or this YouTube explainer). 

Conservatively, the global health calculations also did not include additional benefits from saving health care costs as these data were not reliable on a global level. Productivity gains were also excluded, both domestically and globally, even though the World Bank found them to be substantial in their 2016 report..

Impressively, the core analysis demonstrated such high levels of cost-effectiveness from saving lives that there was no need to resort to secondary benefits.

This is as close to a slam dunk economic analysis as you will ever see. Their analysis is also congruent with the STEDI-based analyses used in the UK’s pilot showing that the high social value of antibiotics is evident even with very conservative estimates. Given their impressive social value, the funding proposed in the PASTEUR Act for compelling new antibiotics is truly a bargain.

—
The report also gives a clear account for why we have a market failure. These 8 key issues summarized on pp.4-6 of the report should be required reading for anyone trying to understand and fix the problem of AMR. Here’s their list along with our commentary:

  1. Initial sales volumes are low. Comment: Good stewardship makes this so; stewardship is great for public health but deadly for R&D companies.)
  2. Most social value is after patent expiry (Comment: This makes it difficult for a company to be appropriately rewarded during the patent period.)
  3. Clinical value is difficult to demonstrate (Comment: This surprises many when they first encounter the problem; for details, see previous newsletters on 19 Sep 2020 and 30 June 2020.)
  4. Traditional reimbursement approaches undervalue new antimicrobials (Comment: See discussions of the STEDI values (aka, the “fire extinguisher” values) of antibiotics in this newsletter and this YouTube video.) 
  5. Common hospital payment mechanisms disincentivize use of novel (more expensive) antimicrobials (Comment: This is an unanticipated impact from the 1983 reforms that bundled hospital reimbursements in Medicare. The DISARM Act would address this issue.)
  6. Point of care diagnostic tests are not being used to reduce drug resistance (Comment: Like unhappy families in Tolstoy’s Anna Karenina, each market failure in AMR is broken in unique ways. For diagnostics, we await the release of the recent US National Academies of Science, Engineering, & Medicine report.)
  7. The science is difficult (Comment: This is undoubtedly true, but the experience of CARB-X suggests that the innovation teams around the world can overcome the scientific challenges if the economics were turned around.)
  8. Regulatory approval processes for new antimicrobials are time-consuming (Comment: While antibiotics might have been at some unique regulatory disadvantage in times past, this is no longer a top-tier reason for why antimicrobial innovation is harder than other drug classes. Regulators will continue to work, but we should celebrate progress to date.)


—
Wow … what a timely and impressive paper! The authors (Towse and Silverman) as well as their funders (Schmidt Futures and Founders Pledge) are indeed to be thanked for this valuable new contribution to the economic arguments in support of delinked Pull awards such as that proposed by the PASTEUR Act. Now let’s just get it passed! Have you written to your Members of Congressx?

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.

Brief summary of the methodology

  1. The annual rate of AMR-attributable deaths was taken from the GRAM project report published earlier this year
  2. Conservatively, they focused on attributable deaths from the 6 leading pathogens causing 79% of these deaths (E. coli, S. aureus, K. pneumoniae, S. pneumoniae, A. baumannii, and P. aeruginosa)
  3. They estimate lost DALYs (disability-adjusted life years) from these deaths using data from the GRAM report.
  4. DALYs are assumed to convert 1:1 to QALYs (quality-adjusted life years) and QALYS are valued at $100k/QALY.
  5. They assume that 18 new qualifying antibiotics are needed over 30 years for for these 6 pathogens (3 new drugs/pathogen) and that:
    • The 18 new qualifying antibiotics appear steadily over that 30 years
    • Each new drug is held completely in reserve for its first 4 years
    • Each new drug reduces deaths/year by 5% from year 5 onward
    • From year 6, each new drug loses effectiveness 2% year-on-year due to emergence of resistance
    • Note that the focus on just the top 6 pathogens conservatively leaves a bit of room in the math for new qualifying drugs to cover more bugs
  6. They assume the Pull Award will provide (on average) a 10-year fully delinked award equal to the $4.2b central “best guess” required value that was estimated in Outterson 2021 “Estimating The Appropriate Size Of Global Pull Incentives For Antibacterial Medicines” (https://www.healthaffairs.org/doi/abs/10.1377/hlthaff.2021.00688).
    • They adjust the numbers for inflation
    • They use the same average value for all antibiotics that earn an award but they explicitly note that the actual reward size would need to be adjusted to reflect the merits of each qualifying antibiotic.
    • Implicit in this discussion of antibiotic value is that antibiotics not providing interesting new coverage of the target pathogens would have zero value, again consistent with the notion that not all drugs would receive a Pull award.
  7. The US fair share of this amount is 46% based on proportion of GDP within the G7 + EU.
    • This equates to $2.1b per drug from the US, a value that is roughly at the mid-point of the $750m to $3b range proposed as part of PASTEUR.

Current funding opportunities (most current list is here)

  • FDA have announced five RFPs spanning antifungal animal models, usability of antimicrobial drug labeling, urine PK-PD, and interpretive breakpoints. Applications are due dates of 23 Jan 2023 — see this newsletter for more details.
  • Current funding rounds from CARB-X are as described in this newsletter!
  • The AMR Action Fund is now open to proposals for funding of Phase 2 / Phase 3 antibacterial therapeutics. Per its charter, the fund prioritizes investment in treatments that address a pathogen prioritized by the WHO, the CDC and/or other public health entities that: (i) are novel (e.g., absence of known cross-resistance, novel targets, new chemical classes, or new mechanisms of action); and/or (ii) have significant differentiated clinical utility (e.g., differentiated innovation that provides clinical value versus standard of care to prescribers and patients, such as safety/tolerability, oral formulation, different spectrum of activity); and (iii) reduce patient mortality. It is also expected that such agents would have the potential to strongly address the likely requirements for delinked Pull incentives such as the UK (NHS England) subscription pilot and the PASTEUR Act in the US. Submit queries to contact@amractionfund.com.
  • BARDA’s long-running BAA-18-100-SOL-00003 offers support for both antibacterial and antifungal agents. This BAA has offered 4 deadlines/year since 2018 … check the most current amendment for details.
  • INCATE (Incubator for Antibacterial Therapies in Europe) is an early-stage funding vehicle supporting innovation vs. drug-resistant bacterial infections. The fund provides advice, community, and non-dilutive funding (€10k in Stage I and up to €250k in Stage II) to support early-stage ventures in creating the evidence and building the team needed to get next-level funding. Details and contacts on their website (https://www.incate.net/).
  • It’s not a funder, but AiCuris’ AiCubator offers incubator support to very early stage projects. Read more about it here.
  • The Global AMR R&D Hub’s dynamic dashboard (link) summarizes the global clinical development pipeline, incentives for AMR R&D, and investors/investments in AMR R&D.
  • In addition to the lists provided by the Global AMR R&D Hub, you might also be interested in my most current lists of R&D incentives (link) and priority pathogens (link).


Upcoming meetings of interest to the AMR community (most current list is here):

  • 27-30 Nov 2022 (Perth, Australia): 32nd International Congress of Antimicrobial Chemotherapy is the biennial congress of the International Society of Antimicrobial Chemotherapy (ISAC). Go here for details.
  • [NEW] 2 Dec 2022 (Harvard, Boston, 9a-6p with reception to follow): BAARN, the Boston Area Antimicrobial Resistance Network. A full day of networking and lectures, including a keynote by Gerry Wright. Go here for details and here to register.
  • 3-7 Dec 2022 (Banff, Canada): Novel Approaches Against Emerging Antimicrobial Resistance by Keystone Symposia. Go here for details. 
  • [NEW] 1-2 Feb 2023 (virtual): Antimicrobial Chemotherapy Conference by GARDP and BSAC in collaboration with ReAct Africa and Africa CDC. Go here for details.
  • 14 Apr 2023 (Copenhagen, Denmark; 3-6.30p CEST): ECCMID and the Global Leaders Group on AMR will jointly sponsor a symposium entitled “Forging partnerships between science and policy in Antimicrobial Resistance (AMR).” Go here to register.
  • 15-18 Apr 2023 (Copenhagen, Denmark): 33rd ECCMID. Go here for details and to register.
  • 8-12 May 2023 (Lisbon, Portugal): 41st Annual Meeting of the European Society for Paediatric Infectious Diseases. Go here for details.
  • [NEW] 14-22 Oct 2023 (residential, Annecy, France): ICARe, the Interdisciplinary Course on Antibiotics and Resistance. Now in its 7th year, this course is a deep-dive into the world of antibiotic development. Intense, rigorous, and HIGHLY recommended. Seats are always limited … apply sooner rather than later! Go here for details.
]]> UK Pull (“Netflix-like”) pilot: STEDI-based QALY value of new antibiotics implies societal value > 10m GBP/year! https://traf-x.amr.solutions/2022/04/11/uk-pull-netflix-pilot-qaly-value-of-new-antibiotics-implies-societal-value-10m-gbp-year/ Tue, 12 Apr 2022 01:40:21 +0000 https://13.43.35.2/?p=7408

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

We’ve written before about the UK’s “Netflix” pilot antibiotic Pull incentive in which England leads the way on showing how it plans to provide its fair share of a global antibacterial Pull incentive (for background on Pull incentives, see this superb 5-minute video explainer).

In an exciting update, NICE has now published the draft guidance for the first two pilot drugs: cefiderocol and ceftazidime-avibactam! Both documents are well worth your time to download and read. In addition, NICE have published this commentary and there’s a also good summary posted by FT.

You may remember that these two drugs were chosen competitively to receive subscriptions of up to £10M each every year for up to 10 years, pending the outcome of economic assessments and a Committee review calculating the societal value of these fire extinguishers of medicine using the STEDI principles (Spectrum, Transmission, Enablement, Diversity, Insurance; for a refresher on STEDI, see this newsletter or this YouTube explainer).

The initial numbers are now in and while there remains work to do, it’s also a moment to celebrate: We don’t (yet) have a specific $/£ value but NICE has stated each drug has a QALY-based value to the NHS in England: for ceftazidime-avibactam it is 530 QALYs/year x 10 years; for cefiderocol, the value is 970 QALYs/year x 10 years. As NICE typically uses £20,000 and £30,000 per QALY as a threshold for the idea of good value (that is, things that cost more than this per QALY are too expensive), a simple scaling of these QALYs/year x £20k/QALY = £11-19M/year. We can see that contract negotiations need to be completed to determine the actual £ figure for each drug (and the actual award will be limited by the £10m/year cap in the pilot program), but it’s evident that the math shows that major new antibiotics have a real social value that can be estimated and should be rewarded!

Pop a cork and raise a glass: we are witnessing the successful maiden voyage of the first antibacterial pull incentive! When the rest of the G7 and (at least some of the) G20 follow suit to bring the global Pull reward into the target range of ~$3b for a substantial new antibiotic, we will have a sustainable solution. Thank you to the entire Team UK! This is what leadership looks like! Woot, woot! 

Note that the economists didn’t quite have all of the data they wanted to calculate some of the STEDI values of antibiotics, so the UK government committee for the project stepped up and made some reasonable estimates. This was precisely the sort of courage needed in the face of some uncertainty, and shines a light on the need to continue to improve both data and methods.

And, that’s why we run Pilot projects: to work out the kinks and to prepare the way to do better next time. Who wants to go next? The PASTEUR ACT in the US is poised to happen in 2022 … as an early sign, the 2023 US budget recently proposed by the White House includes a proposal that “… would provide annual payments from a contract valued between $750 million and $3 billion to the developers of newly approved antimicrobial drugs” — this is, of course, exactly the PASTEUR concept! With Canada, Europe, and Japan also taking steps, we are seeing the momentum build.

it’s just stunning to contemplate how far we’ve come since the 17 Sep 2009 conference hosted by Sweden on Innovative Incentives for Effective Antibacterials. IDSA had sounded the Bad Bugs, No Drugs call in 2004, but there was really zero momentum on global solutions until the meeting in 2009 triggered a cascading series of actions by multiple stakeholders: New Drugs for Bad Bugs (ND4BB)! CARB-X! DRIVE-AB! UK AMR Review! Novo REPAIR Impact Fund! GARDP! The Global AMR R&D Hub! The IACG on AMR! The $1b AMR Action Fund!

And now we see the creation of the first true Pull incentive that would make it possible for new #FireExtinguishersOfMedicine to reach registration, stay on the market, and be available to the many who will desperately need them! As stated in the NICE commentary: “The NHS will now use its commercial power to secure deals that will enable NHS patients to benefit from these treatments, delivering on its Long Term Plan commitment and paving the way for a pipeline of future treatment options.”

Our world is beset with many vexing problems; the broken economics of antibiotics is a problem we can truly start to fix in 2022. 

We’ll say it again: Woot, woot! WELL DONE, TEAM UK!

All best wishes, Kevin and 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.

Current funding opportunities (most current list is here):

  • JPIAMR’s 14th call is now open. Entitled “Disrupting drug resistance using innovative design”, the call seeks consortia that would seek to “improve the treatment of bacterial and fungal infections (including co-infection) and/or the prevention of the emergence/spread of resistance in humans, animals or plants through the improvement of the efficacy, specificity, delivery, combinations and/or repurposing of drugs and plant protection agents.” Bacteria, fungi, human health, animal health, and plant health are all in scope! Pre-proposals are due 8 Mar 2022; full proposals would be due 5 July 2022. Go here for details.
  • The AMR Action Fund is now open to proposals for funding of Phase 2 / Phase 3 antibacterial therapeutics. Per its charter, the fund prioritizes investment in treatments that address a pathogen prioritized by the WHO, the CDC and/or other public health entities that: (i) are novel (e.g., absence of known cross-resistance, novel targets, new chemical classes, or new mechanisms of action); and/or (ii) have significant differentiated clinical utility (e.g., differentiated innovation that provides clinical value versus standard of care to prescribers and patients, such as safety/tolerability, oral formulation, different spectrum of activity); and (iii) reduce patient mortality. It is also expected that such agents would have the potential to strongly address the likely requirements for delinked Pull incentives such as the UK (NHS England) subscription pilot and the PASTEUR Act in the US. Submit queries to contact@amractionfund.com.
  • INCATE (Incubator for Antibacterial Therapies in Europe) is a newly launched early-stage funding vehicle. Details are still coming into focus, but per comments on 25 Aug 2021 at the BIOCOM conference, their goal is to support ~4 companies per year with about $250k/company. Contact details are on their website (https://www.incate.net/).
  • CARB-X recently announced that their existing resources will be reserved to fund their existing portfolio (more than 80 total awards, and counting, as they include contracting from prior rounds). New rounds from CARB-X will occur only after new funding is obtained in 2021.
  • It’s not a funder, but AiCuris’ AiCubator offers incubator support to very early stage projects. Read more about it here.
  • The Global AMR R&D Hub’s dynamic dashboard (link) summarizes the global clinical development pipeline, incentives for AMR R&D, and investors/investments in AMR R&D.
  • In addition to the lists provided by the Global AMR R&D Hub, you might also be interested in my most current lists of R&D incentives (link) and priority pathogens (link).


Upcoming meetings of interest to the AMR community (most current list is here):

  • 8 Dec 2021: “The New Winds Pushing and Pulling Antibacterial Development.” This FABULOUS program featured talks from the UK team behind the NHS “Netflix” pilot, Kevin Outterson’s recently released report documenting the need for global Pull incentives to have a value of $2.2 – 4.8b, and speakers covering PASTEUR and work in the EU on pull incentives. The video is here — please make time to listen to this program!
  • The stunning 4 Feb 2022 webinar for the GRAM report (Global Research on Antimicrobial Resistance “1.27 million deaths per year are directly attributable to AMR”) is now available for replay. #AMRSOS! 
  • 23-26 Apr 2022 (Lisbon): 32nd European Congress of Clinical Microbiology & Infectious Diseases (ECCMID). Go here for details.
  • 9-13 May 2022 (Athens and online): 40th Annual Meeting of the European Society for Paediatric Infectious Diseases, Go here for details.
  • 16-18 June 2022 (Perth, Australia): Australasian Society for Infectious Diseases Annual Scientific Meeting is a hybrid event for adult and pediatric infectious disease and clinical microbiology specialists. Go here for details.
  • 11-14 July 2022 (Sydney): Australian Society for Microbiology Annual National Meeting is a hybrid event that will feature a range of lectures and symposium sessions, as well as extensive opportunities for networking. Go here for details.
  • 24-27 July 2022 (Il Ciocco, Tuscany): Gordon Research Conference entitled “New Antibacterial Discovery and Development”. Go here for details, go here for the linked 5-6 Mar Gordon Research Seminar that precedes it.
  • 28-31 July 2022 (Singapore): 10th International Congress of Asia Pacific Society of Infection Control is a hybrid event for professionals in the Asia Pacific region. Go here for details.
  • 20-24 Sep 2022 (New Delhi): 21st Congress of the International Society for Human and Animal Mycology (ISHAM). Go here for details.
  • [NEW] 4-7 Oct 2022 (Dublin, Ireland): The 2022 ASM/ESCMID Joint Conference on Drug Development to Meet the Challenge of Antimicrobial Resistance. This is an excellent meeting, especially for developers … and if you’ve missed it, the recordings from the 2021 meeting are online. Go here for details on the 2022 meeting.
  • 19-23 Oct 2022 (Washington, DC): IDWeek 2022, the joint annual meeting of the Infectious Diseases Society of America (IDSA), Society for Healthcare Epidemiology of America (SHEA), the HIV Medicine Association (HIVMA), the Pediatric Infectious Diseases Society (PIDS), and the Society of Infectious Diseases Pharmacists (SIDP). Go here for details.
  • 15-23 Oct 2022 (in person, residential, Les Pensières, Veyrier-du-Lac, France): The 6th edition of Patrice Courvalin’s fabulous ICARe residential training course covering all things AMR is on for 2022! This is a soup-to-nuts training in AMR: it is very intense, very detailed, and always gets rave reviews from attendees. Registration is open 21 Mar 2022 to 21 June 2022 and is limited, so book your slot as soon as you can. Go here for more: https://www.icarecourse.org/
  • 19-23 Oct 2022 (Washington, DC): IDWeek 2022, the joint annual meeting of the Infectious Diseases Society of America (IDSA), Society for Healthcare Epidemiology of America (SHEA), the HIV Medicine Association (HIVMA), the Pediatric Infectious Diseases Society (PIDS), and the Society of Infectious Diseases Pharmacists (SIDP). Go here for details.
  • 25-28 Oct 2022 (Stellenbosch, South Africa): The University of Cape Town’s H3D Research Centre will celebrate its 10th anniversary with a symposium covering the Centre’s research on Malaria, TB, Neglected Tropical Diseases, and AMR. Go here to register.
  • 27-30 Nov 2022 (Perth, Australia): 32nd International Congress of Antimicrobial Chemotherapy is the biennial congress of the International Society of Antimicrobial Chemotherapy (ISAC). Go here for details.
]]> Appropriate pull incentive for new antibacterials: $2.2-4.8b for full delinkage https://traf-x.amr.solutions/2021/11/01/appropriate-pull-incentive-for-new-antibacterials-2-2-4-8b-for-full-delinkage/ Tue, 02 Nov 2021 00:54:07 +0000 https://13.43.35.2/?p=6474

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

Readers of these newsletters will need few reminders of why pull incentives are critical to restoring the R&D ecosystem for antibacterials. (But if you are new to the issue, Andrew Jack’s 5-minute video explainer is a great start; see also this annotated list of newsletters on incentives).

Across all the debates about how create a pull incentive, a persistent question has been: What is the appropriate size for these pull incentives? Underpay, and we risk failure; overpay, and we’ve wasted taxpayer money.
 
That question is the subject of my research article out today in Health Affairs, the highest-ranked health policy journal. Entitled “Estimating The Appropriate Size Of Global Pull Incentives For Antibacterial Medicines,” the paper’s key conclusions are:

  • Prior reports (ERG, O’Neill, DRIVE-AB, BCG, WHO) underestimated the required size of pull incentives through a combination of factors, including unrealistically low manufacturing and post-approval costs, overestimating revenues, overestimating the success rate for preclinical R&D, and not accounting for the cost of the market sales that are not delinked (thus mistakenly concluding that partially delinked awards are overall cheaper than fully delinked subscription programs). For the record, I was a co-author on two of these reports!
  • The key takeaway: A combination of push and pull incentives totaling several billion dollars per drug are required globally.
  • For a fully delinked global subscription program, the optimal size for a global pull incentive is $2.2 to $4.8 billion, with a best estimate of $3.1 billion.
  • Partially delinked market entry rewards come in with lower direct cost best estimate of $1.6b but this cost ignores the impact of acquisition costs in the marketplace. 
  • If other wealthy countries also contribute their fair share, the UK subscription (“Netflix”) program and the proposed PASTEUR ACT in the US will be effective and efficient, as they are well within bounds of these estimates.

 
For more information, see the article, the online supplement, and the the open-access Excel model behind the paper. Wonkish details on the model are found below the signature block. In addition, the paper will be discussed in these settings over the next couple weeks:


This is a critical moment in the global Push-Pull conversation! Based on the substantial Push incentives deployed over the past ~5 years, there are now many interesting prospects for new antibiotics. But, all this energy will come to a crashing halt if we don’t address the final problem by deploying suitable Pull incentives. Having a good estimate of the fair value to global economies of a new antibiotic is pivotal to supporting the political discussion needed to finally create these incentives.

All best wishes, Kevin

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

With administrative support from 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.

— FURTHER DETAILS —
 
The Model. The article deploys an expected Net Present Value (eNPV) model for antibacterial R&D, similar to the methods in most major studies on pull incentives over the past decade. And for good reason: this is how pharmaceutical companies make financial go/no-go decisions on R&D. The Model begins at Hit-To-Lead, including all phases to first regulatory approval and beyond to generic entry, a total of 26 years. For each phase, out-of-pocket costs are incurred over a predicted duration, with a predicted probability of technical and regulatory success in the current phase. After approval, sales revenue begin to come in, as do post-approval costs. All of these costs and revenues are discounted back to the eNPV at the decision point. Companies should not proceed if the eNPV is negative or if there are other available projects with higher eNPVs.
 
Transparency. All aspects of the model are published with this article, including all data, coding, parameters, and the Dashboard. This allows for full transparency in all assumptions so that other researchers can replicate this research and improve it as better data become available.
 
Funding. This work was solely funded by the sabbatical research program at Boston University School of Law. While Pfizer gave me an internal eNPV model, all coding decisions were mine alone. This is my academic work, and does not necessarily represent the opinions of CARB-X or any CARB-X funder.

Current funding opportunities (most current list is here):

  • The AMR Action Fund is now open to proposals for funding of Phase 2 / Phase 3 antibacterial therapeutics. Per its charter, the fund prioritizes investment in treatments that address a pathogen prioritized by the WHO, the CDC and/or other public health entities that: (i) are novel (e.g., absence of known cross-resistance, novel targets, new chemical classes, or new mechanisms of action); and/or (ii) have significant differentiated clinical utility (e.g., differentiated innovation that provides clinical value versus standard of care to prescribers and patients, such as safety/tolerability, oral formulation, different spectrum of activity); and (iii) reduce patient mortality. It is also expected that such agents would have the potential to strongly address the likely requirements for delinked Pull incentives such as the UK (NHS England) subscription pilot and the PASTEUR Act in the US. Submit queries to contact@amractionfund.com.
  • INCATE (Incubator for Antibacterial Therapies in Europe) is a newly launched early-stage funding vehicle. Details are still coming into focus, but per comments on 25 Aug 2021 at the BIOCOM conference, their goal is to support ~4 companies per year with about $250k/company. Contact details are on their website (https://www.incate.net/).
  • CARB-X recently announced that their existing resources will be reserved to fund their existing portfolio (more than 80 total awards, and counting, as they include contracting from prior rounds). New rounds from CARB-X will occur only after new funding is obtained in 2021.
  • It’s not a funder, but AiCuris’ AiCubator offers incubator support to very early stage projects. Read more about it here.
  • The Global AMR R&D Hub’s dynamic dashboard (link) summarizes the global clinical development pipeline, incentives for AMR R&D, and investors/investments in AMR R&D.
  • In addition to the lists provided by the Global AMR R&D Hub, you might also be interested in my most current lists of R&D incentives (link) and priority pathogens (link).


Upcoming meetings of interest to the AMR community (most current list is here):

  • [CONTENT UPDATE] 2 Nov 2021 (virtual, 8-9.30a US East Coast, noon-1.30p London, 1-2.30p Paris, 9-10.30p Tokyo): Pfizer-sponsored webinar entitled “The Global AMR Crisis: Is the scale of the action matching the scale of the threat?” With speakers including Hanan Balkhy (WHO), Ramanan Laxminarayan (CDDEP), Hon. Yasuhisa Shiozaki (multiple Cabinet-level roles in Japan’s government, Prof. Lothar H. Wieler (President, Robert Koch Institute), David Paterson (Director, U Queensland Centre for Clinical Research), Kevin Outterson (CARB-X), and me, this event will (i) discuss how the right incentives can simultaneously stimulate both improved patient access as well as innovation in anti-infectives and (ii) provide practical frameworks to support implementation of national action plans. Don’t miss this one … it is also the debut discussion of Kevin Outterson’s recently released report documenting the need for substantial global Pull incentives for antibacterial agents! Go here to register!
  • [NEW] 10 Nov 2021: (virtual, 3pm East Coast US): Health Affairs journal club Kevin Outterson’s recently released report documenting the need for substantial global Pull incentives as a part of the ecosystem that ensures a sustained pipeline of novel antibacterial agents. Link is pending — watch the Health Affairs Journal Club page for details.
  • 15-17 Nov 2021 (virtual, timings TBD but would expect global coverage): 3rd Call to Action on Antimicrobial Resistance: “Sharing evidence and best practice to empower national action.”
    • Building on the success of the previous Call to Action on Antimicrobial Resistance (AMR) conferences held in Berlin (2017) and Ghana (2018), the governments of Denmark, Colombia, Ghana and Zambia, with the International Centre for AMR Solutions (ICARS), UN Foundation, UNICEF, and the Wellcome Trust, are together organising a follow-up event to advance the response to rising rates of drug-resistant infections.
    • Go here for an  expression of interest form; contact the organizers at AMRCalltoAction@wellcome.org for other details.
  • [NEW] 16 Nov 2021 (virtual, 2-3.30p CET): Hosted by Reuters Events, this EFPIA-sponsored webinar entitled “Pandemic Prevention: how Europe can lead the fight against AMR” features a strong EU-focused panel (e.g., European Patients Forum, BEAM Alliance) with also CARB-X and the AMR Action Fund. Go here for full details, here to register.
  • [NEW] 17 Nov 2021 (virtual, noon-2p East Coast US): Duke-Margolis webinar entitled “Ensuring Pull Incentives for Priority Antibiotics Succeed.”  Mark McClellan will moderate; discussion will focus on (i) tailoring pull incentives for priority antibiotic development and (ii) the need for pull incentives beyond the US and UK. Of key importance, the webinar will feature a discussion of Kevin Outterson’s recently released report documenting the need for substantial global Pull incentives (for fully delinked models, these should be in the range $2.2 – 4.8b). Here is the agenda; go here to register.
  • 18-24 Nov 2021: World Antimicrobial Awareness Week (WAAW), sponsored by WHO. The theme is “Spread awareness, stop resistance.” Go here for details.
  • 1 Dec 2021 (virtual, 9a-1p UK): Westminster Health Forum policy conference “Tackling antimicrobial resistance in the UK and the UK’s role on the global stage.” Chaired by Kevin Hollinrake MP (Co-Chair, All-Party Parliamentary Group on Antibiotics, APPG-Antibiotics) and Professor the Lord Trees, Emeritus Professor, U Liverpool; and Treasurer, APPG-Antibiotics, this 5-h session includes keynotes from Dame Sally Davies and Haileyesus Getahun (WHO) and speakers spanning the UK’s AMR efforts. Go here to register.
  • [NEW] 1 Dec 2021 (virtual, 4-5p CET): Spotlight session at ISPOR 2021 entitled “Methods to Estimate the Value of New Antibiotics in the Context of Antimicrobial Resistance.” ISPOR is the International Society for Pharmacoeconomics and Outcomes Research and this spotlight session at their annual meeting will feature discussions of the modeling used by the UK in support of its “Netflix” delinked purchase pilot model. Go here to register if you are interested in the whole meeting; I am working to try to make this specific session free to access by streaming after the session.
  • 3 Dec 2021 (Boston, in person, 9a-6.30p, COVID vaccination required): 8th annual BAARN (Boston Area Antimicrobial Research Network) meeting. Go here for details; registration link is here.
  • 3 Dec 2021 (virtual, US daytime timings): Symposium entitled “Advances in Antibacterial Discovery” sponsored by the St. Jude Department of Chemical Biology and Therapeutics, is a part of the broader Bringing Chemistry to Medicine series and is supported by the St. Jude T32 Infectious Disease Therapeutics training program. Go here for details and to register.
  • [NEW] 8-9 Dec 2021 (virtual, 9a-noon East Coast US): ASM-ESCMID-sponsored joint conference on antimicrobial drug development. This is the 2021 online version of one of my favorite meetings and I strongly encourage attendance on both days to gain a perspective on how new reimbursement models are going to change the R&D landscape. Online agenda is here, registration link is pending so just mark your calendar for now.
    • [NEW] 8 Dec: “The New Winds Pushing and Pulling Antibacterial Development.” DO NOT MISS THIS ONE! Featuring (i) talks from the UK team behind the NHS “Netflix” pilot, (ii) Kevin Outterson’s recently released report documenting the need for fully delinked global Pull incentives to have a value of $2.2 – 4.8b, and (iii) speakers covering PASTEUR and work in the EU on pull incentives, this promises to be a key update for the whole community.
    • [NEW] 9 Dec: CARB-X – GARDP Boot Camp: What Makes a Good Project Succeed? Featuring speakers with many years of R&D experience, this session makes a good companion to the 8 Dec talk and will leave you well informed on best ways to guide your search for new antibiotics.
  • 3-6 Mar 2022 (Albuquerque, New Mexico): Biannual meeting of the MSGERC (Mycoses Study Group Education and Research Consortium). Details are here.
  • 6-11 Mar 2022 (Il Ciocco, Tuscany): Gordon Research Conference entitled “New Antibacterial Discovery and Development”. Go here for details, go here for the linked 5-6 Mar Gordon Research Seminar that precedes it.
  • 7-8 Apr 2022 (Basel and in person, we hope): The 6th edition of the annual AMR conference sponsored by the BEAM Alliance, CARB-X, the Novo REPAIR Impact Fund, the IMI Accelerator, and the European Biotechnology Network. Go here for the hold-the-date page and a way to be kept informed about the meeting. 
  • 9-13 May 2022 (Athens and online): 40th Annual Meeting of the European Society for Paediatric Infectious Diseases, Go here for details.
  • 20-24 Sep 2022 (New Delhi): 21st Congress of the International Society for Human and Animal Mycology (ISHAM). Go here for details.
  • 25-28 Oct 2022 (Stellenbosch, South Africa): The University of Cape Town’s H3D Research Centre will celebrate its 10th anniversary with a symposium covering the Centre’s research on Malaria, TB, Neglected Tropical Diseases, and AMR. Go here to register.
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