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.

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