Scary, Scarier, Scariest: Achaogen / FT editorial / CBS “60 Minutes” on AMR

There is a follow-up to this note.  Go here to read it.

Dear All: I don’t like writing about doom and gloom, but a sequence of events in the past few days really drives home both the importance of the work we do to create new antibiotics as well as the fragile state of the ecosystem supporting that work. Here we go…

Scary: Alan Carr today posted a superb summary of Achaogen’s bankruptcy (html version, pdf version; you might also want to review his recent broader survey of the antibiotic sector). If you’ve not followed the Achaogen story closely, the key plot line is that the company (a) developed plazomicin (Zemdri), a novel intravenous aminoglycoside antibiotic with activity against carbapenem-resistant Enterbacteriaceae (CRE), (b) brought it successfully through registration to US approval, (c) had sales of $0.8m during 2018 and (d) declared bankruptcy (link) last week. As you read his full note, focus on the timeline:

  • “Achaogen initiated clinical development of Zemdri in 2009 with a focus on CRE.”
  • “Achaogen initiated a Phase 3 trial of Zemdri against colistin in CRE in 2014 (CARE trial)” but this trial was difficult to enroll with “2100 patients screened and 37 randomized over 2.5 years.”
    • Aside: When this study started in 2014, the only antibiotic on the market with even moderately reliable activity for CRE was colistin, an ancient and toxic antibiotic from the polymyxin class.
  • “A Phase 3 cUTI trial completed in Dec 2016 demonstrated impressive efficacy relative to meropenem (EPIC trial).”
  • “Allergan and Melinta launched Avycaz and Vabomere in 2015 and 2017.”
    • Aside: Avycaz and Vabomere are intravenous antibiotics that also cover CRE. Notably, they are both from the beta-lactam antibiotic class whereas Zemdri is from the aminoglycoside class.
  • “Zemdri was launched in the U.S. in Jul 2018.”
  • “Achaogen filed for Chapter 11 bankruptcy last week (April 2019).

Note how long it takes to bring a new antibiotic to market. It’s also expensive: per an estimate from Alan (personal communication), Achaogen raised around $450m in VC and public funds from founding to bankruptcy, not counting non-dilutive support and debt. Then, note that Zemdri is an especially welcome addition to the very small number of agents for CRE by virtue of being a different class of antibiotic relative to Avycaz & Vabomere (beta-lactam class) and colistin (polymyxin class). Finally, note how Alan summarizes the market dynamics for these four agents:

  • “Avycaz gained traction in the CRE market, but four years after launch, polymyxins still dominate.
  • “We assumed Vabomere and Zemdri would displace Avycaz and accelerate a decline in polymyxin use.
  • “Instead, polymyxin use is stable while Vabomere and Zemdri are essentially not used at all.”

So, what went wrong (and is still going wrong) here? We’ll doubtless be talking about this at many future meetings, but the basis for a key paradox can be seen in the slow recruitment into the CARE trial of plazomicin vs. colistin for CRE: 2,100 screened to enroll 37 … and at a cost (by verbal report) of $70m. While we do need new drugs for CRE, we work really hard in parallel to make CRE infections rare and hence it is difficult to run a study of CRE. And, of course, we also do everything we can to limit use of new antibiotics once approved.

For more on this complex topic, please see my current lecture (link) on Funding, Filing, and Finance, especially slides 11-15. And also be sure to attend the 6-9 Sep ASM-ESCMID Conference on Antibiotic Development (link) where one of the Bootcamp sessions on 3 Sep will focus on post-approval antibiotic economics. For now, we need to move on to…

Scarier: Yesterday (21 Apr 2019), Jeremy Farrar, Director of Wellcome Trust, wrote an editorial in the Financial Times (link)

  • The editorial briefly reviews the Achaogen story.
  • The editorial’s core theme: “There is no viable path for new drugs, however valuable they are to society.”

Yes, and Achaogen would certainly seem to be the poster child for this! The editorial concludes by calling for “creative new models to stabilise the antibiotics market and stimulate private sector innovation without exposing public funders to all the risk.” For more on the approaches that are needed and especially the lonely state of Pull incentives, see this note (link). And with this we come to…

Scariest: Finally, and also yesterday, CBS aired a superb 60 Minutes episode on AMR (link). In it, you can see:

  • E. coli becoming visibly resistant to ciprofloxacin over about 10 days,
  • Colistin purchased over-the-counter in Delhi, and
  • How easy it is for any of us to acquire highly resistant bacteria, especially during global travel.

The clip in which the reporter purchases OTC colistin is stunning. 

Inhale, exhale, and keep working. All best wishes, –jr

John H. Rex, MD | Chief Medical Officer, F2G Ltd. | Expert-in-Residence, Wellcome Trust. Follow me on Twitter: @JohnRex_NewAbx. See past newsletters and subscribe for the future:

Upcoming meetings of interest to the AMR community:

  • 24-26 Apr 2019 (Boston): Annual SHEA (Soc. for Hospital Epidemiology of America) Spring meeting
  • 6-11 May 2019 (Ljubljana, Slovenia): 37th Annual Meeting of the European Society for Paediatric Infectious Diseases (ESPID). Details here.
  • 20 May 2019 (everywhere): Application deadline for NIAID solicitation (HHS-NIH-NIAID-BAA2019-1) for proposals to support new vaccine or therapeutics candidates targeting antibiotic-resistant bacterial infections. Go here for more details.
  • 3-6 Jun 2019 (Philadelphia): Annual BIO meeting
  • 20-24 June 2019 (San Francisco): Annual ASM Microbe meeting.
  • 10-11 Jul 2019 (Madison, WI): Tiny Earth Symposium, a teaching consortium that uses crowd-sourcing of antibiotic-producing microbes to improve undergraduate education. Details here.
  • 12 July 2019 (FDA, White Oak Campus): Public workshop to discuss the 2018 LPAD guidance. Register here.
  • [Mark your calendar now!] 3-6 Sep 2019 (Boston). Annual ASM-ESCMID Conference on Antibiotic Development. The Bootcamp series will continue on 3 Sep with main meeting on 4-6 Sep. Mark your calendar now and check back here for details.
  • 6-8 Sep 2019 (Bilbao, Spain): 5th ESCMID conference on Vaccines. Check back here for details.
  • 2-6 Oct 2019 (Washington, DC): IDSA’s annual IDWeek meeting.
  • 19-27 Oct 2019 (Annecy, France): International Course on Antibiotics and Resistance (ICARe) – A soup-to-nuts intensive residential training program on all things AMR, especially R&D for new antibiotics. See this link for details.
  • [Mark your calendar now!] 1-6 Mar 2020 (Il Ciocco, Tuscany, Italy): GRC on Antibacterial Discovery and Development: “Now is the time to re-boot antibiotic R&D before it’s too little, too late.” Not yet online, but the date is firm. Will share a link when it becomes available.
  • 12-13 Mar 2020 (Berlin?): BEAM-, Novo REPAIR-, CARB-X-, DZIF-, ND4BB-, ENABLE-supported (among a long list!) Conference on Novel Antimicrobials and AMR Diagnostics. Final location is TBD, details will appear here, and you should mark your calendar now. 
  • 18-21 Apr 2020 (Paris): Annual ECCMID meeting (#30)
  • 10-13 Apr 2021 (Vienna): Annual ECCMID meeting (#31)

Dear All,
The IDWeek 2024 program committee is again seeking programs on novel antimicrobial agents and novel diagnostics for presentation in pipeline sessions! Here’s what is sought:

  • “Industry partners are invited to submit antimicrobials that are in preclinical stages of development (Phase II and III preferred) or recently approved after January 2024.
  • “The pipeline sessions will include antibacterials, antifungals, and antivirals (excluding COVID-19 and HIV).
  • “The committee also invites companies developing novel diagnostic technologies with a minimum of some preliminary proof of concept data to submit.” 

This is a great opportunity to tell the story of your development project! The deadline to submit is Wednesday, June 26 via the application portal. Any questions should be directed to Please share this email with anyone you think might be interested in applying!
In addition, I’ll also note that those with a more general story to tell should look at the BugHub Stage (and the Global BugHub stage). Both BugHub variants seek “presentations that touch on your experience of working in infectious diseases and presentations that ultimately lead to a greater understanding of our diverse field” via a TED Talk-esque speech about your work. The deadline for applications is 26 June, the same as for the pipeline sessions.

I look forward to seeing you there! 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: All opinions are my own.

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!

  • 27-30 April 2024 (Barcelona, Spain): 34th ECCMID, the annual meeting of the European Society for Clinical Microbiology and Infectious Diseases. Go here for details. 
  • 17-20 Sep 2024 (Porto, Portugal): ASM/ESCMID Joint Conference on Drug Development to Meet the Challenge of Antimicrobial Resistance. Go here for the meeting’s general website. You can’t register (yet) for the 2024 event, but save the date!
  • 16-20 Oct 2024 (Los Angeles, USA): IDWeek 2024, the annual meeting of the Infectious Diseases Society of America. Save the date! More details to come!
  • 25-26 February 2025 (Basel, Switzerland): The 9th AMR Conference 2025. Go here to register

Upcoming meetings of interest to the AMR community:

  • [NEW]  9 Apr 2024 (virtual, 830a-10a ET): GARDP’s next REVIVE webinar entitled “Progressing a discovery project – Criteria and challenges.” Register here.
  • [NEW] 9 Apr 2024 (virtual, 10a-1130a ET): CDC webinar “Impacts of Antimicrobial Resistance on Cancer Care.” Click here for details and to register.
  • 10-11 Apr 2024 (virtual): Sepsis Alliance AMR Conference, a 2-day conference focused on “Practical technologies to manage sepsis and counteract the expanding challenge of antimicrobial resistance.” Go here for details and to register.
  • 26 Apr 2024 (Barcelona, Spain): ESCMID workshop entitled “Using Data Science and Machine Learning for Infection Science: A Hands-on Introduction.” Click here to register or here for more details. 
  • 27-30 April 2024 (Barcelona, Spain): 34th ECCMID, the annual meeting of the European Society for Clinical Microbiology and Infectious Diseases. See Recurring Meetings list, above.
  • 26-31 May 2024 (Montreal, Canada): EDAR7, the McGill AMR Centre’s 7th edition of their Environmental Dimension of Antimicrobial Resistance conference. Go here for details; final abstract deadline is 21 Dec 2023.
  • 28-29 May 2024 (in person, Uppsala, Sweden): Uppsala Antibiotic Days, a broad-ranging 2-day program hosted by the Uppsala Antibiotic Center. Go here for details and to register.
  • [NEW] 30-31 May 2024 (face-to-face in Rockville, Maryland as well as online, 8.30-5.30p ET on 30 May, 9-2.40p on 31 May): NIAID-sponsored workshop entitled “Towards realizing the promise of adjunctive immune therapy for invasive fungal infections”. The agenda covers host immunity to invasive fungal infections, immune modulators in the context of fungal infections; and strategies for testing immune modulators as adjunctive therapy. Go here for more details and to register.
  • 9-13 June 2024 (in person, Ascona, Switzerland): “New Approaches to Combat Antibiotic-Resistant Bacteria, 2nd Edition” is a Sunday-Thursday residential workshop focused on the deep biology of AMR. Sponsored by NCCR AntiResist (a Swiss National Science Foundation consortium), the scientific program has the feel of a Gordon Conference. Space is limited, so you are encouraged to apply promptly — go here for details.
  • 13-17 June 2024 (Atlanta, Georgia): ASM Microbe, the annual meeting of the American Society for Microbiology. You can’t register yet, but you can go here for general details.
  • 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.
  • 16-20 Oct 2024 (Los Angeles, USA): IDWeek 2024, the annual meeting of the Infectious Diseases Society of America. See Recurring Meetings list, above. 
  • 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; the agenda is comprehensive and features an all-star global list of speakers.


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