Dear All, It’s been a busy 48 hours .. three (and a half) things for you!
First up, you will find notes below my signature on today’s “Antimicrobial Resistance: Examining an Emerging Public Health Threat” hearing in the US House of Representatives. The recording of today’s hearing is now available on YouTube. It was a fabulous 2 hours of discussion about AMR and I highly recommend listening to it when you have the time. In my notes, I include links to particular time stamps in the video should you want to hear more about the subjects discussed.
Second, the PASTEUR Act has been reintroduced! As you may recall, all pending legislation dies at the end of each 2-year session of Congress. As PASTEUR did not pass during the 117th Congress, it needed to be reintroduced to the 118th (current) session. Done!
Helpfully, the Wall Street Journal released an article about the push for the PASTEUR Act. The article is short, excellent summary for the uninitiated. Definitely shareworthy on your social media!
Third, and as well-timed and very pertinent perspective on the way that long-term efforts reap dividends, CARB-X has released its annual report. The report is beautifully laid out and has some great graphics. It is wonderful to see that CARB-X has been very busy strengthening the R&D chain. Amazing progress — please make time to look through the report itself!
As to that final half … there are very exciting things afoot in the EU with an AMR-related proposal from the European Commission … stay tuned for a separate newsletter on same!
YOW! Well done to all involved and particularly to those involved in today’s hearing! Exciting times!
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/. All opinions are my own.
== Detailed Notes from today’s hearing of the House E&C Committee ==
During the opening comments, I found it very instructive to hear the various ways that the members of the subcommittee became interested in AMR. Opening statements were given by Chair Griffith, Ranking Member Castor, Chair Rodgers, and Ranking Member Pallone. Each opening statement recognized the threat that is AMR while also highlighting that there was a need to understand how to improve current US government efforts. Chair Griffith made a particular remark that this was about fact finding, not promoting legislation (even though PASTEUR was mentioned several times as part of answers during the Q&A). Their interest in AMR was evident and several mentioned the fact that COVID-19 has sparked an overall public interest in pandemic preparedness. There were remarks about the hearing that had happened yesterday afternoon in regards to the value of this. And with that, we were off to the Q&A!
Each summoned witness gave short statements before the floor opened for questions. Each read an opening statement; you may also want to read their written Witness Testimony here. Think of the testimonies as assigned reading for the hearing!
First up was Mary Denigan-Macauley of the US Government Accountability Office (GAO). The GAO has been making motions to increase federal funding to fight AMR for several years now. A GAO report to Congress in March 2020 provided an in-depth report about the US government efforts to monitoring antibiotic resistance and what needed to change in order for the country to counter spread of AMR. This report was referenced multiple times during the hearing so make sure to add that to your reading!
She highlighted 4 key areas for improvement which were a) the precise magnitude of this problem is not known and data is not complete, b) limitations on diagnostics in terms of development and use, c) the R&D pipeline is weak and it needs to be fixed (and, non-traditional therapies need to be investigated), and d) Antibiotic stewardship and monitoring needs to be improved.
Next was Kevin Outterson of CARB-X who spoke of resistance eating away at antibiotics like rust on a bridge and that we “put [new antibiotics] on a shelf, behind glass like they are a fire extinguisher”. This naturally segued into paying for antibiotics like fire extinguishers and how we don’t currently do that as a society. He pushed for a subscription program and, by proxy, the PASTEUR Act. “It’s time to invest in the future of antibiotics again.” Agreed!
Up next was Amanda Jezek of IDSA who highlighted some infection statistics before advocating for good antimicrobial stewardship. She mentioned staffing of ID physicians at hospitals as part of good stewardship and that the lack of ID physicians across the country was an issue. She also noted how poor pay and medical student debt were contributing to the issue. Phage therapy and additional research should also be pursued as a possibility. During a quick microphone fix, she mentioned off-hand that “ID people are used to dealing with the unexpected”. Truer words have never been said!
Finally, Amy J. Mathers of the University of Virginia School of Medicine spoke on behalf of the American Society for Microbiology (ASM). As a frontline physician, she spoke of her experience with patients that have drug-resistant bugs and also her work with promoting good antibiotic stewardship at her hospital. She advocated for better research and diagnostics to help counter AMR. Staffing shortages and interest as AMR as a career are a problem — “we need more people post-pandemic in the clinical lab.”
Now, to the Q&A —
- Chair Griffith opened his 5 minutes of questioning by mentioning his own interest in AMR was sparked by reading a book! The book in question is The Perfect Predator by Steffanie Strathdee and Thomas Patterson which is a memoir of a couple’s experience with a lethal superbug. Phage, creativity in clinical trial designs, the need for sharing of clinical data, the value of a patient-based hearing, and finding another magic bullet were all discussed.
- Ranking Member Castor used her time to focus on diagnostics and surveillance. Fax machines need to be phased out! But also how much information is needed and when will we decide we have enough to understand a developing situation?
- Chair Rodgers spoke of the ongoing work on AMR within the government and asked about the GAO’s examination to what extent that these efforts were coordinated. As part of her answer, Mary Denigan-Macauley noted that surveillance reporting needs to include discussion of failures and shortcomings as well as successes.
- Ranking Member Pallone asked about lessons that can be drawn from COVID-19. As part of her excellent answer, Amy Mathers said “I feel mistrust from patients. It feels like somebody else is at the bedside…There’s just a lot of misinformation that’s been out there that has impacted trust” and “I think antimicrobial resistance awareness is such a complicated issue, it doesn’t fit the soundbite.”
- Representative Guthrie used his time to discuss the US AMR National Action Plan and how that work has progressed. He also wanted to understand how CARB-X chooses what projects to back and how they acquire funding.
- Representative Tonko wanted to mention the late Louise Slaughter who was a microbiologist and was passionate about AMR. He shared the story of a young patient who was diagnosed with cystic fibrosis before noting the allocation of funds from the US Budget for fiscal year 2024 to federal AMR efforts. Kevin Outterson noted that “[CF patients] aren’t dying from cystic fibrosis anymore, they are dying from resistant lung infections” and we need novel drug classes in order to help resolve this issue. Amy Mathers spoke of how federal investments have helped to combat AMR.
- Representative Cammack asked about natural disaster preparedness and AMR. Food spoilage, safe water, emergency shelters are crowded, and serious burns from wildfires were mentioned by Amanda Jezek. “We need tools in the toolbox to deal with these infections so we need those novel antimicrobial therapies and we need experts who know how to use them…because hours matter in infectious disease”. Rep. Cammack was also concerned about national security and if there was one area above all others that was most important to focus on. Mary Denigan-Macauley made it clear that we need a One Health approach to deal with AMR and, while there have been great efforts already, more needs to be done to handle this issue.
- Represenative Schakowsky brought up geriatric populations, Medicare, and the general overuse of antibiotics.
- “The death certificate does not say AMR, it says something else” – Kevin Outterson on advocating for better reporting.
- Representative Burgess wanted to discuss the difficulty of explaining AMR to patients, the spread of Valley Fever, possible lessons from other countries, diagnostics.
- Representative Ruiz asked about global collaboration and efforts to solve AMR. Mary Denigan-Macauley noted that “they turn to us as leaders so if the US doesn’t take action, then other countries do get worried“. He was then interested in how to spread out ID physicians and resolve the staffing issues.
- Representative Palmer was concerned about communication about avoiding overuse of antibiotics and wanted to understand current reporting standards. He also wanted to understand how antibiotics should be purchased moving forward to encourage development as well as how AMR could possibly effect the US military. The idea that a soldier could survive the battlefield only to die from an infection in the hospital seemed to resonate deeply!
- Representative Lesko asked about medical school education about AMR and the efforts of IDSA to educate. She also wanted Kevin Outterson to share the achievements of CARB-X (see the annual report that just came out!).
- Representative Armstrong wanted to discuss AMR and veterinary medicine.
- Representative Carter was concerned about the overuse of antibiotics. As a supporter of of the PASTEUR Act, he asked for a brief summary of Push/Pull incentives … and Kevin provided just that! As part of this discussion, Amanda Jezek spoke to factors causing the overuse of antibiotics … and, with that, the hearing was closed!
Current funding opportunities (most current list is here)
- [UPDATED – New application round] CARB-X again has an open-round for funding applications with a deadline of 1 May 2023. Applications are sought for any of 3 themes (oral products, vaccines for neonatal sepsis, gonorrhea products) 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 firstname.lastname@example.org.
- 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):
- 8-12 May 2023 (Lisbon, Portugal): 41st Annual Meeting of the European Society for Paediatric Infectious Diseases. Go here for details.
- 3-5 Jul 2023 (Tours, France): 9th Symposium on Antimicrobial Resistance in Animals and the Environment (ARAE). Sponsored by INRAE (French National Research Institute for Agriculture, Food, and Environment, itself a merger of merger of INRA, the French National Institute for Agricultural Research, and IRSTEA, the French National Research Institute of Science and Technology for the Environment and Agriculture), this conference has been running since 2005. Go here for details.
- [NOW OPEN FOR APPLICATIONS!] 7-15 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.
- 20-23 Oct 2023 (Athens, Greece): 11th TIMM (Trends in Medical Mycology). Go here for details.