Updated ATMF AMR Benchmark! Signs of progress but access lags

Dear All (and with thanks to ATMF’s Damiano de Felice for co-authoring this newsletter),


Last week, the team at ATMF (Access to Medicine Foundation) released a 3rd update to the AMR Benchmark series that they started in 2018. For those not familiar with the ATMF, its independent analyses (all its funding is from governments or private foundations) are widely used by companies to benchmark their activities against peers and learn from best practices. To follow along, here are the links you need:


This year’s report offers a wealth of granular data, in-depth analyses and revealing graphs about what the biggest pharmaceutical companies in the global antibiotic and antifungal markets are doing to tackle the rise of AMR and the global need for appropriate access to antimicrobials. You can find a high-level summary of the main findings, with some comments, in the paragraphs below. Further (wonkish!) details, with links to relevant past newsletters, can be found below the signature block.

  • On R&D, the report confirms that (i) the AMR pipeline of ‘big pharma’ companies grew modestly but remains small compared to the scale of the AMR threat and (ii) most innovation is in smaller biotech companies.
    • This is not bad considering the negative trend of the past decades. The urgent need for appropriate pull incentives (e.g., PASTEUR Act) remains: we need the resources and capabilities of multinational companies to bring new products to patients in multiple markets across the world, and we cannot take the risk of losing even more companies while we wait. The AMR Action Fund will help in the interim but it, too, is ultimately dependent on global implementation of good pull incentives.
  • A very positive finding of the report is about gains in planning for stewardship and access. Encouraged (we think) by ideas such as those proposed in the CARB-X Stewardship and Access Plan (SAP) Development Guide, SAPs now cover 18 of the 20 medicine candidates in Phase II or beyond!
    • This is a significant improvement since the first Benchmark analysis (2018)!
    • As a further drive for having an SAP, the AMR Action Fund committed to a specific set of Access and Stewardship Principles as well.
  • With respect to manufacturing, the pharmaceutical industry is making greater efforts to curb the release of APIs (active pharmaceutical ingredients) into wastewater. This is encouraging, even though a very small number of suppliers’ factories are, as yet, reported as being compliant with AMR limits.
    • Here, the report identifies a role for public procurers to ensure responsible manufacturing practices when buying anti-infectives. For more on this, note the intriguingly entitled webinar “How procurement can contribute to reduced emissions from the pharmaceutical industry” on 25 Nov 2021 (10-11am Sweden) from the Swedish Procurement Agency.
  • Frustratingly, access to both on-patent and off-patent antibiotics and antifungals continues to lag in both LMICs and the developed world.
    • The surprising delays in the developed world were highlighted in this 19 Aug 2021 newsletter.
    • Resolving this requires actions at many levels of the AMR ecosystem. Governments and international organisations should definitely do more as well to create better market conditions in all countries across the income spectrum – a new initiative worth mentioning here is SECURE, in addition to the many National Action Plans supported by the WHO. Best practices for pharma include ideas such as tech transfer for local manufacturing as discussed here.
  • Like access, stewardship requires actions across the AMR ecosystem, and some companies play their part by managing the way they set incentives for sales representatives and by avoiding conflicts of interest when contributing to educational activities for healthcare professionals.
    • Companies can also contribute with data to guide stewardship. Here Pfizer is leading the way by publicly sharing the raw data from its largest surveillance programme (ATLAS) on the AMR Register, an open-access data platform, and partner with Wellcome to make this data actionable through the SPIDAAR and GRAM projects (see also this 29 June 2020 newsletter on that project). Other companies with large surveillance datasets (e.g., MSD, GSK, Shionogi, JNJ) could join these efforts.


As you can see, the report has plenty of actionable information across multiple topics! We encourage you to read it fully and reach out to the Access to Medicine Foundation in case you have any questions about the research process.

All best wishes, John and Damiano

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.

Damiano de Felice, PhD | Director of Strategy, Access to Medicine Foundation. Follow me on Twitter: @damidefelice. All opinions are my own.

 === FURTHER DETAILS ===
R&D

  • “Among the eight large research-based companies, the Benchmark identified 92 R&D projects [medicines and vaccines] that target infections caused by ‘priority pathogens’ … This is a modest increase on 2020, when the same eight companies were developing a combined 77 projects.” Moreover, “[o]ne third (18) of the 54 projects that remained in the pipeline from the 2020 analysis have progressed to the next stage of development.” We all know that this is not enough to keep up with the emergence and spread of drug-resistant infections, and that these numbers are minuscule in comparison to the pipeline from these companies in other disease areas (e.g., cancer). Yet, it is positive to see that there are signs of continued investments from the few companies remaining active in the field, such as Pfizer acquiring Arixa and Amplyx, and investing in ContraFect (for the negative trend of disengagement during the past decades, see this 15 Sep 2019 newsletter).
  • Still, “75% of the antibacterial and antifungal R&D pipeline targeting priority pathogens is being developed by small biotech companies.” This is aligned with the results of other pipeline reviews, including from WHO (more details in this 14 Apr 2021 newsletter) and Pew (more details in this 10 Mar 2021 newsletter). Earlier this year, the ATMF published another report about the challenges that these smaller companies face to bring their products to the market and survive at the same time (more details in this 14 Jun 2021 newsletter), which is a problem that we discussed extensively in past newsletters, e.g., about Achaogen and Melinta. The case of Cipla withdrawing its marketing application for plazomicin (ZEMDRI) clearly showed that the most likely outcome for an approved antibacterial agent is bankruptcy for the developer and limited or no access to the drug for all of us (see 11 Jul 2020 newsletter). The hope is that new pull incentives in the US with the PASTEUR Act (16 Nov 2021 newsletter), in Europe with the new Pharmaceutical Strategy for Europe (5 Oct 2021 newsletter) and in other G7 countries will significantly improve the value for ‘big pharma’ companies acquiring smaller companies and replenishing their pipeline (if the size of the incentive will be appropriate, see 1 Nov 2021 newsletter for the latest estimates). Let us keep our fingers crossed! In the meantime, the AMR Action Fund will likely provide a crucial lifeline for some clinical-stage companies (18 Feb 2021 newsletter).
  • “Plans to address the access to and stewardship of new products in countries with high disease burdens have become common, now covering 18 of the 20 medicine candidates in Phase II or beyond. This is a significant improvement since the first Benchmark analysis, published in 2018, when only a handful of projects were covered by plans.” This is a clear sign that the work of the ATMF with the AMR Benchmark is bearing fruits, in conjunction with similar expectations and practical guidance put forward by partners like CARB-X and Wellcome (see 22 Mar 2021 newsletter about the publication of the Stewardship & Access Plan Development Guide, a document which outlines what can be reasonably expected of product developers in relation to stewardship and access).

Manufacturing

  • “There are 1,057 manufacturing sites in scope, consisting of 187 of the companies’ own sites (based on data from 15 companies) and 807 supplier sites (based on data from 12 companies). The majority of sites are reported to be subject to discharge limits. However, less than a third of all sites are reported as quantifying discharge levels to determine compliance with limits, while 13% are reported as compliant with the limits set. Focusing in on suppliers’ sites, the ‘compliance gap’ or ‘data gap’ becomes clear. Whereas 97 out of the pharma companies’ 187 directly-operated sites included in this analysis are reported as compliant (52%), just 45 of the 870 suppliers’ sites are reported as compliant (5.2%).”
  • Wastewater discharge is not a topic that we have covered many times, but this 19 Dec 2018 newsletter summarised some interesting research on the potential for the environment (e.g., soil and water) to be a source of antimicrobial-resistant microbes that can affect human health and this 22 Dec 2019 newsletter on a JPIAMR project on Aquatic Pollutants..

Access

  • Of the products in scope, only 35% of on-patent medicines have been filed for registration in more than 10 LMICs. And only 39% of off -patent/generic medicines supplied by large research-based companies are filed in more than 10 LMICs. For products in scope which are marketed by generic medicine manufacturers, that number drops down to 29% filed in more than 10 LMICs. Moreover, “[o]nly one third (54) of the pharma companies’ 166 antibacterial and antifungal products in scope are covered by any ‘access strategy’ in any of the 102 low- and middle-income countries where better access to antimicrobial products is most urgently needed.”
  • These findings are upsetting (not only patients suffer but also lack of appropriate access forces doctors to use suboptimal treatments, giving pathogens further opportunities to develop resistance). Unfortunately, they are not surprising. Even G7 and other high-income countries in Europe have troubles accessing new and old antibiotics (see 19 Aug 2021 newsletter and 7 Sep 2020 newsletter).

Stewardship

  • “The Benchmark previously reported an increase in the number of pharmaceutical companies that had stopped the use of sales agents altogether, or had decoupled agents’ bonuses from sales volume. In 2021, three more generic medicine manufacturers took action to combat overselling: Abbott, Aurobindo and Viatris. … A range of strategies are now being implemented across the industry, for example pilots for full decoupling, or no promotion in some countries and/or for some products. However, the true impact of these pilots remains unknown. Further progress is still needed toward full decoupling, or towards a policy of no promotion to healthcare professionals globally.”
  • Pfizer leads on publicly sharing raw surveillance data via its ATLAS project on the AMR Register, an open-access data platform. Other companies could add to this: GSK and Shionogi have pledged to share raw surveillance data; MSD and JNJ also run or contribute to large surveillance programmes.
  • The fact that Shionogi and Pfizer are among the leaders in this area may not surprise the readers of this newsletter, given that the products of these two companies were selected for the UK pilot and the UK government made it clear that access and stewardship practices (as evaluated in the Benchmark) were part of the criteria used during the selection process (see 18 Dec 2020 newsletter). We also highlighted the importance of Pfizer’s work sharing the raw data of its ATLAS surveillance programme in this 29 Jun 2020 newsletter: “this is a first of its kind public-private partnership supporting surveillance in countries with limited capacity and capability and is proof of how multiple sectors can come together to address AMR.”

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):

  • 18-24 Nov 2021: World Antimicrobial Awareness Week (WAAW), sponsored by WHO. The theme is “Spread awareness, stop resistance.” Go here for details. 
  • 24 Nov 2021 (virtual, 9-10a New York / 3-4p Paris): Webinar sponsored by the Global Coalition on Aging and MSD entitled “AMR Threat to National Health Systems and Economies: A Call-to-Action.” The webinar will feature a discussion of GCOA’s 2021 AMR Preparedness Index as well as an upcoming report entitled “Developing National Strategies to tackle Antimicrobial Resistance across countries in the Eastern Europe, Middle East and Africa (EEMEA) region.” Go here to register.
  • 24 Nov 2021 (virtual, 10a CET and also 3.30p CET): WHO-sponsored webinar entitled “Applying behavioural and cultural insights to tackle antimicrobial resistance.” Register here for the 10a webinar, here for the 3.30p edition. I find this to be a fascinating topic … good for WHO!
  • [NEW] 24 Nov 2021 (virtual, 10a-11a Sweden): Webinar entitled “How procurement can contribute to reduced emissions from the pharmaceutical industry” from the Swedish Procurement Agency. Go here for details.
  • 26 Nov 2021 (virtual, 9.30a-12.30p, EU-centric timing): Webinar entitled “Horizon Europe Tackling Diseases and Antimicrobial Resistance (AMR) Webinar and Partnering – Cluster 1 / Destination 3 and 5′. Multiple calls for consortia participation (vaccines, pandemic preparedness, and more) as well as discussion of an upcoming JPIAMR Therapeutics Call that is expected to be announced on 18 Nov 2021. Go here to register.
  • [NEW] 30 Nov-1 Dec 2021 (virtual, 10a-3.30p EST on both days): US PACCARB (Presidential Advisory Council on Combatting Antimicrobial Resistant Bacteria) is holding a 2-day meeting that includes updates from the Global Leaders Group (GLG), the World Health Organization (WHO), and the recent National Academies report entitled “Examining the Long-term Health and Economic Effects of Antimicrobial Resistance in the United States”. This sounds like an excellent update! Go here for details and to register.
  • 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.
  • 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.
  • 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.
    • 8 Dec: “The New Winds Pushing and Pulling Antibacterial Development.” DO NOT MISS THIS ONE! Featuring 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, this promises to be a key update for the whole community.
    • 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.
  • 14 Dec 2021 (virtual, 9a-1030a EST): CDC webinar entitled “Hooves, Paws, or Feet: A Multispecies Examination of Antimicrobial Use and Stewardship Practices”. This event is the third installment of the AMR Exchange webinar series. Click here for details.
  • 2-3 Feb 2022 (virtual): 10th Advances Against Aspergillosis and Mucormycocosis. Registration closes on 30 Jan 2022. Go here for details.
  • 2-3 Feb 2022 (virtual): Antimicrobial Chemotherapy Virtual Conference jointly organised by GARDP with the British Society for Antimicrobial Chemotherapy (BSAC), Center for Disease Dynamics, Economics & Policy (CDDEP) and the Indian Council of Medical Research (ICMR). Click here for details.
  • 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 AllianceCARB-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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