Dear All (and heads-up for a rather lengthy and wonkish note … settle in for the details),
Last week saw substantial AMR-related news released in / around the Davos 2020 World Economic Forum. A brief summary follows, with some supplemental details below my signature.
- Access to Medicine Foundation (ATMF) released their 2nd scorecard on industry actions to address AMR
- Highlight: In her opening essay entitled The Fragile Antibiotic Market Has Reached a Tipping Point (link), ATMF Executive Directory Jayasree Iyer points to the idea that Access requires Innovation when she says “… large and prominent drugmakers have retreated from the antibiotics field and smaller innovative biotech companies have gone bankrupt … tough market conditions must be replaced through a mix of public and private investment to ensure a healthy ecosystem of pharmaceutical innovation, production and supply.”
- For more: Go here for the ATMF website and here for their report (the report is nearly 10MB, so be patient).
- The AMR Industry Alliance (AMR IA) has released their 2nd progress report on industry commitments and actions
- Highlight: Despite investments of $1.6b during 2018 from AMR IA companies plus public investment of approximately $0.5b in support of > 60 new products, companies, “Current investments are not enough to drive a sustainable and robust R&D ecosystem for antibiotics, and investments may further decrease in the coming years if market conditions remain unchanged.”
- For more: Go here for the AMR IA website, here for the press release, and here for the report itself.
- On 21 Jan 2020, Novo sponsored a panel discussion at Davos on AMR (link).
- The panel is about an hour in length, was chaired by Kevin Outterson (Executive Director, CARB-X and Professor of Law, Boston University), and features comments by Jeremy Farrar (Director, Wellcome Trust), Lars Rebien Sørensen (Chairman, Novo Holdings and the Novo Nordisk Foundation), Malin Grape (Public Health Agency of Sweden), Jayasree Iyer (Executive Director, Access to Medicine Foundation), and Thomas Cueni (Director General of IFPMA).
- (i) A consistent call by all speakers for public and private funding to ensure a viable ecosystem. On this point, it was interesting to hear two large foundations (Novo and Wellcome) describe the problem beyond their capabilities and make the case that public funding is also needed.
- (ii) Sweden is developing a partially delinked model for antibiotic purchases (see further notes just below).
- (iii) Kevin Outterson framed the problem as solvable for only $2-3B per year from global governments, a very achievable number compared to other important global issues like climate change.
Let me also point out /remind you of these parallel events, both of which also highlight the need to reimburse differently for antibiotics:
- The delinkage actions of the Public Health Agency of Sweden (PHAS) mentioned by Malin Grape during the Davos discussion are new and intriguing. As background, PHAS published a 2017 report (link) calling for a study of models to ensure antibiotic availability.
- Details beyond the brief comments at Davos are scant but I did find two online comments.
- First is a brief note online (link) dated 14 Nov 2019 that describes “a public procurement process which is planned to be completed in spring 2020” seeking to ensure that the Swedish healthcare system will not risk being without active antibiotics via a new reimbursement model which guarantees a minimum annual revenue to the pharmaceutical company in return for delivery of a certain amount of antibiotic within specified time limits.
- Second is a LinkedIn commentary (link) by Aleks Engel (Director, Novo REPAIR Impact Fund) in which he shows a diagram laying out a simple guaranteed revenue model.
- Fascinating … I am eager to learn more!
- Last week’s Duke-Margolis workshop (link) was consistent with the Davos panel discussion but also included a verbal update on the progress of the UK’s NHS-NICE antibiotic subscription model. I then heard a further presentation on 22 Jan from Team NICE about their progress towards their subscription model. In brief, the plan as summarized in my 29 Nov 2019 note (link) remains on track with a goal of signing contracts with two companies by 1Q21.
Although these reports and conversations may seem repetitive and it may seem that progress is slow, it is important to remember that NONE of this was underway even 5 years ago. Rather, this is progress and it is these sorts of events that will repair the antibiotic ecosystem. If you want to learn more and only have limited time, I highly recommend the Davos panel discussion (link) — the calls for public and private collaboration are notable in their clarity and alignment.
With all best wishes, –jr
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/
Further details: Progress report from the AMR Innovation Alliance (AMR IA; go here for their website, here for the press release, and here for the report itself). Established in 2017, the AMR IA encompasses about 100 companies, 20 trade associations, and about half of the AMR-focused product work being done globally. AMR IA was founded on commitments in 4 areas (Research & Science, Access, Appropriate Use, and Manufacturing & Environment) and this report summarizes data collected during 2019 regarding company activities.
In a forward to the AMR IA report, Dame Sally Davies notes that “The battle against the growing challenge of AMR may well be won or lost in the next decade.” It is thus encouraging to learn that 2018 private investments of $1.6b from AMR IA companies were matched by public investment of approximately $0.5b to support development of > 60 new products.
But, Dame Sally further notes that “Current investments are not enough to drive a sustainable and robust R&D ecosystem for antibiotics, and investments may further decrease in the coming years if market conditions remain unchanged.”
The AMR IA report is divided into 4 sections. There’s a lot of detail in each, but here are key points by section:
- R&D: Supported in part by public funds (see just above), Industry has invested heavily at least through 2018. Note that it may well be a much smaller amount in 2019; there is real angst about the future of the companies. See also prior notes about the bankruptcy of Melinta (link) and Achaogen (link).
- Access: This one is hard to summarize, but comprehensive access strategies are widely implemented, often via partnering with governments and NGOs
- Appropriate Use: Appropriate use and stewardship plans are reported by most companies, as are revisions to promotional activities to align with stewardship (e.g., removing volume-based incentives for sales personnel)
- Manufacturing: AMR IA committed to and now has published (2 years ahead of plan) predicted no-effect concentrations (PNECs) which can be used to establish discharge targets for antibiotic manufacturing sites.
Further details: 2020 scorecard from the Access to Medicine Foundation (ATMF; go here for the website and here for the report; the report is nearly 10MB, so be patient!). Reinforcing the themes highlighted by Dame Sally in the introduction to the AMR IA progress report, Executive Director Jayasree K. Iyer titles her introduction to the ATMF scorecard “The Fragile Antibiotic Market Has Reached a Tipping Point” and she goes on to say:
- “… large and prominent drugmakers have retreated from the antibiotics field and smaller innovative biotech companies have gone bankrupt…
- “…disinvestment and industry consolidation has created an increasingly fragile manufacturing and supply chain…
- “This second Benchmark provides a reality check … tough market conditions must be replaced through a mix of public and private investment to ensure a healthy ecosystem of pharmaceutical innovation, production and supply.”
The goal of the ATMF scorecard is to evaluate pharmaceutical companies “in areas where they have the biggest potential and responsibility to limit AMR, such as R&D, managing manufacturing waste and ensuring appropriate access and stewardship. ATMF used a variety of metrics (R&D investments, Pipeline size, Novelty, Projects targeting critical pathogens, Access and stewardship planning) to score the activities of 8 large research-based pharma companies and 13 small/medium-size enterprises. Here are their key findings from the Executive Summary:
- “The clinical pipeline of antibiotics for priority infections remains small, but companies have plans for access and stewardship in place for more of them than in 2018. Eight out of 32 key candidate antibiotics (25%) have such plans, up from 2 out of 28 (7%) in 2018. However, such advance planning is so far benefitting only a few diseases.
- “Companies are missing opportunities to make antibiotics available, by not seeking to register new antibiotics in countries where the need is greatest and by not widely supplying to lower-income countries older antibiotics that are still clinically useful.
- “There is progress in responsible promotion practices that address the overselling of antibiotics. By decoupling bonuses from sales volumes, or not using any sales staff at all, companies mitigate against overselling antibiotics and driving resistance. Ten companies now take such steps. That compares with five companies taking such action in 2018.
- “More companies are supporting or running AMR surveillance programmes that track the rise and spread of resistance, and most publish the results. Pfizer has become the first company to share the raw data, publishing it on an open-access AMR online register.”
Notable in the ATMF metrics is the focus on novelty and priority pathogens. With featuring heavily in reviews from WHO (link) and Pew (link), neither of these ideas should be a surprise. But as discussed in my 17 Jan 2020 notes on the WHO review (same link), true novelty is rare and we should not overlook the value to be gained by improvements on known classes.
Across the ATMF and AMR IA reports, another notable element is that Industry is working steadily towards Access and Stewardship. I was especially interested in the discussion of Access on pages 20-23 of the ATMF report. A subtitle here is “Pharmaceutical companies are not registering new antibiotics where need is greatest.”
Although access is a multifaceted problem that spans more than regulatory approvals (go here for a CDDEP study on same), I wonder if there might not be a flip side to this … what are LMICs (Low and Middle-Income Countries) doing to make it straightforward to be on the market? Could initiatives such as the African Medicines Regulatory Harmonisation (AMRH, link) or the Pan-American Network for Drug Regulatory Harmonization (PANDRH, link) help turn the corner? The level of effort required to make and maintain regulatory filings in any given country is a significant lift! Along these lines, the recent announcement that Swissmedic would in some cases scale back its review procedure for US- or EU-approved Infectious Diseases vaccines (link) is relevant. All good food for thought!
Upcoming meetings of interest to the AMR community:
- 21 Jan 2020 (1700-1830 CET, online): GARDP-sponsored webinar entitled “Testing for the potential of emergence of resistance.” Go here to register.
- 28-29 Jan 2020 (Rockville, MD, NIAID campus): Two-day workshop entitled “Understanding the Biology, Antifungal Resistance and Clinical Implications of Candida auris.” Draft agenda is here and registration is here.
- [NEW] 7 Feb 2020 (1700-1830 CET, online): GARDP-sponsored webinar entitled “Non-traditional antibacterial therapeutic options and challenges.” Go here to register.
- 12 Feb 2020 (Alderley Park, UK): “2020 Bioinfect Conference” sponsored by Bionow (link), the NW England life science accelerator. Go here to register.
- 20 Feb 2020 (London, UK): Westminster Health Forum conference entitled “Antimicrobial resistance – coordinating a global response and progress on the UK strategy.” Go here for details.
- 24 Feb 2020 (London, UK): One-day workshop hosted by Royal College of Nursing and the Longitude Prize entitled “Developing point-of-care diagnostics for urinary tract infections (UTIs): addressing clinical need in the UK.” Register here.
- 26-27 Feb 2020 (Washington, DC): US PACCARB public meeting. Go here for details.
- 27 Feb 2020 (1700-1830 CET, online): GARDP-sponsored webinar entitled “PK/PD murine infection models: Focus on study elements, variability, and interpretation of results.” Go here to register.
- 1-6 Mar 2020 (Il Ciocco, Tuscany, Italy): Gordon Research Conference (GRC) on Antibacterial Discovery and Development: “Now is the time to re-boot antibiotic R&D before it’s too little, too late.” Go here for details.
- 12-13 Mar 2020 (Basel): BEAM-, Novo REPAIR-, CARB-X-, DZIF-, ND4BB-, ENABLE-supported (among a long list!) Conference on Novel Antimicrobials and AMR Diagnostics. Details are here, poster deadline is 12 Dec 2019.
- 16-17 Mar 2020 (London): BSAC Spring Conference entitled: “Bridging the gap between science, policy and effective antimicrobial use.” Go here for details.
- 26-30 Mar 2020 (Atlanta, GA): CDC- and SHEA-sponsored 6th International Conference on Healthcare Associated Infections. Go here for details.
- 30 Mar 2020 (everywhere): Deadline for applications for the Molecular Mycology pathogenesis course at Marine Biological Laboratory, Woods Hole. Now in its 24th year, the hands-on residential course runs 17 July to 2 Aug and gets rave reviews. Go here for more.
- 9 Apr 2020 (everywhere): Final date for applications for NIAID/DMID call (link) for AMR-related vaccines, therapeutics, and diagnostics.
- 18-21 Apr 2020 (Paris): Annual ECCMID meeting (#30)
- 25-30 May 2020 (Rotterdam), Annual ESPID meeting (European Society for Pediatric ID, #38)
- 18-22 Jun 2020 (Chicago), ASM Microbe 2020. Go here for details.
- 27-28 Jun 2020 (Bryant University, Rhode Island): Drug Resistance Gordon Research Seminar entitled “Mechanisms and Approaches to Overcoming Drug Resistance in Cancer, Infectious Disease and Agriculture” for graduate students and postdoctoral scientists. Go here for details … this immediately precedes the GRC listed just next
- 28 Jun-3 Jul 2020 (Bryant University, Rhode Island): Gordon Research Conference (GRC) entitled “Strategies to Disrupt Drug Resistance in Infectious Disease, Cancer and Agriculture.” Go here for details.
- 1-4 Sep 2020 (Dublin): Annual ASM-ESCMID Conference on Antibiotic Development #5! Mark your calendar now and go here for details.
- 9-10 Sep 2020 (Washington, DC): US PACCARB public meeting. Go here for details.
- 22-25 Sep 2020 (Albuquerque, New Mexico): Biannual meeting of the MSGERC (Mycoses Study Group Education and Research Consortium). Save-the-date announcement is here, details to follow.
- 17-25 Oct 2020 (Annecy, France): Interdisciplinary Course on Antibiotics and Resistance (ICARe). This is a soup-to-nuts residential course on antibiotics, antibiotic resistance, and antibiotic R&D. The course is very intense, very detailed, and gets rave reviews. The date is set for 2020 and the program will ultimately appear here. Registration is limited to 40 students and opens 15 Mar 2020.
- 10-13 Apr 2021 (Vienna): Annual ECCMID meeting (#31)
- 3-7 Jun 2021 (Anaheim), ASM Microbe 2021. Go here for details.