From an IV arsenical to PO fexinidazole for Sleeping Sickness: A doctor’s dream

Dear All,

As those of us who have had the privilege of standing at the bedside and delivering care know first hand, the magical power of a safe and effective antimicrobial agent is little short of magic. Sometimes, the (nearly) dead can get up and walk!

With that idea in mind, I was just blown away this evening by a film that won a Grand Prix award at the 12 May 2020 inaugural WHO Health for All film festival. The film (link to see it now on YouTube) is a marvelous 7.5-minute tour of the DNDi-sponsored project that led to the development of fexinidazole (an oral therapy for Human African Trypanosomiasis, HAT, aka Sleeping Sickness), a devastating parasitic infection. The human star of the film is Dr Victor Kande, the Neglected Tropical Diseases Expert Advisor to the Ministry of Health of the Democratic Republic of Congo (DRC) as well as the principal investigator of the fexinidazole trials. But, the real star is the incredible team of people who delivered the tools and training required to implement a GCP (Good Clinical Practice)-compliant trial in the DRC.

The film (link, same as above, just in case you missed it, and be ready to cry as you watch), is put into text/visual story form here: https://stories.dndi.org/sleepingsickness-doctors-dream/.

As the film and text make clear, the arsenical melarsoprol (think Paul Ehrlich, very first antibiotic class ever discovered, Salvarsan, Compound 606, and Out of Africa) that was the standard therapy for decades was discovered in the 1940s. While melarsoprol did cure some patients, it was IV-only, would burn your skin if not handled properly, felt like “fire in the veins” as it was administered, and killed about 1 in 20 who received it!

Approved in 2018 (link), fexinidazole is an oral, once daily, 10-day therapy that replaced both melarsoporol and NECT (link), a combination IV and PO non-arsenical therapy introduced in 2009 by DNDi. Talk about a paradigm shift … from IV to IV+PO to all PO; from fighting fire with fire (the vein-burning melarsoprol) to a fighting fire with a simple (seemingly — but think of the enormous effort behind it) pill. Yow!

Well done to all involved … and please share the link to this short film. As the world is learning right now during the COVID-19 pandemic, the lack of a good antimicrobial (fire extinguisher) can be devastating. The resilience of our AMR community never ceases to amaze me … please get busy and invent that new class antimicrobial agent!

All best wishes, –jr

PS: There were also a number of other clever submissions and award winners at the Film festival: Check them out here!

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.

Current funding opportunities:

  • Dates for the 2020 funding rounds for Novo REPAIR Impact Fund will be announced May 2020. Go here for current details.
  • 2020 funding rounds for CARB-X have not been announced.
  • The Global AMR R&D Hub’s dynamic dashboard (link) summarizes funders and projects by geography, stage, and more.


Upcoming meetings of interest to the AMR community:

  • 12 May 2020 (online, 17:00-18:30 CEST): GARDP REVIVE webinar. Title: “Probability of target attainment analyses for dose selection in antimicrobial drug development.” Speaker: Shampa Das. Go here to register.
  • 19 May 2020 (online, 17:00-18:30 CEST): GARDP REVIVE webinar. Title: “Assay development for measuring antibiotic accumulation in Gram-negative bacteria.” Speakers: Jessica Blair, Mark Bronstrop, David Six. Go here to register.
  • [NEW] 28 May 2020 (online, noon-1p EST): CARB-X webinar. Title: “How to Prepare for an FDA Pre-IND Meeting: Planning for Success.” Speakers: Carmella Moody and Michael Bevilacqua. Go here to register.
  • 9 Jun 2020 (online, 17:00-18:30 CEST): GARDP REVIVE webinar. Title: “Test tube to patient: PK/PD of fixed dose beta-lactam/beta-lactamase inhibitor combinations.” Speaker: Vincent Tam. Go here to register.
  • 30 Jun 2020 (online, 17:00-18:30 CEST): GARDP REVIVE webinar. Title: “Clinical development of antimicrobials – Phase 1 development challenges.” Speaker: Markus Zeitlinger. Go here to register.
  • 9 Jul 2020 (online, 09:00-10:30 CEST): GARDP REVIVE webinar. Title: “The challenges and opportunities for antimicrobial R&D in low- and middle-income countries – India case study.” Speaker: Anand Anandkumar and Kamini Walla. Go here to register.
  • 17 Jul-2 Aug 2020 (Marine Biology Laboratory, Woods Hole, MA): Residential course entitled “Molecular Mycology: Current Approaches to Fungal Pathogenesis.” This 2-week intensive training program has run annually for many years and gets outstanding reviews. Go here for details.
  • 29 Jul-2 Aug 2020 (Philadelphia, PA): Small World Initiative Instructor Training Workshop – training for undergraduate professors and high school teachers in wet lab techniques, parallel curricula, pedagogical instruction to engage students in the hunt to find new antibiotics in soil. Go here to register.
  • 4 Aug 2020 (Silver Spring): FDA workshop entitled “Development Considerations of Antifungal Drugs to Address Unmet Medical Need.” Go here to register.
  • 5 Aug 2020 (Silver Spring): FDA workshop entitled “Developing Antifungal Drugs for the Treatment of Coccidioidomycosis (Valley Fever) Infection.” Go here to register.
  • September 2020. University of Sheffield (UK). Applications are being taken for a new 1-year (full-time) or 2-year (part-time) Masters of Science course in Antimicrobial Resistance. The program runs annually from September and covers microbiology, clinical practice and policy. The course webpage is here.
  • 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.
  • 26-29 Oct 2020 (Rotterdam), Annual ESPID meeting (European Society for Pediatric ID, #38)
  • 10-13 Apr 2021 (Vienna): Annual ECCMID meeting (#31)
  • 20-24 June 2021 (Toronto): International Symposium on Pneumococci and Pneumococcal Diseases (ISPPD-12). Go here for details.
  • 3-7 Jun 2021 (Anaheim), ASM Microbe 2021. Go here for details.
  • 8-11 Oct 2021 (Aberdeen, Scotland): 10th Trends in Medical Mycology. Go here for details.
  • 16-24 Oct 2021 (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. Registration is here and is limited to 40 students.

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 program@idsociety.org. 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: https://amr.solutions/blog/. 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 https://fungaldx.com/; the agenda is comprehensive and features an all-star global list of speakers.

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