Updated ATMF AMR Benchmark! Signs of progress but access lags

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:

• The PDF of the report itself
• The AMR Benchmark website (go here for interactive features such as a motivational list of best practices)
• For context on how the report is used, here are some examples:
  • Corporate interest in using the results to benchmark their work is evident in this 2019 workshop hosted by ATMF
  • The previous iteration of the Benchmark was well received at the World Economic Forum in 2020
  • The Investor Action on AMR Initiative held a virtual event last week at which the report was discussed

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.”