As recently summarized by Pew Trusts’ reviews of the antimicrobial pipeline, there is a lot of interest in non-traditional (alternative) antimicrobial agents but there has also been a lot of concern that they are harder to develop than more traditional agents. If you’ll permit me to (briefly) coin the term Fleming Antibiotic to describe things like penicillin, I find it helpful to approach the challenge of non-traditional products by envisioning a continuum defined by these ideas:
- Fleming antibiotic:
- Qualitatively, is like a penicillin in that it has the spectrum for a defined syndrome and the speed required to be suitable as standalone therapy (SSSS, if you like acronyms)
- By virtue of these properties, it is readily developed as monotherapy using standard non-inferiority trial designs.
- Non-Fleming = non-traditional = everything else
- This category captures anything not completely having the Spectrum-Syndrome-Speed-Standalone properties of a Fleming Antibiotic.
- This can include phage, antibodies, small molecules, large molecules, microbiome … it doesn’t matter. It’s non-Fleming because of what it does (or, rather, what it does NOT do).
- Most often used in combination with a base therapy and hence may have to be studied in a trial where it is possible to see superiority of the combination relative to the base therapy alone. Showing this type of superiority can be very challenging!
I’ll admit to having long been fascinated by the potential for non-traditional products: the idea of, for example, a virulence factor inhibitor really appeals to me! But, and as was discussed in Czaplewski et al. “Alternatives to antibiotics—a pipeline portfolio review”, LancetID, 2016), such products are often hard to develop because of issues such as the need to show superiority, the very narrow spectrum of some products, and/or product effects that are not well captured by the clinical endpoints used in our trials.
If this tension resonates with your work, you will be interested in knowing about two upcoming discussions of non-traditional products.
First, there is an interactive session on Sunday 22 Apr 2018 during ECCMID (Madrid, 9-11am, Hall G) entitled “Expediting antibacterial development: core lessons and key tools for a rocky road.” In a session co-sponsored by CARB-X and GARDP, there will be talks by Marco Caveleri (EMA), Sumati Nambiar (FDA), and William Hope (PK-PD guru). I am the 4th speaker and will be covering the problem of non-traditional products. I am working closely with my co-speakers on this talk with the goal of presenting a good perspective on possible approaches. I’m also going to work with my co-speakers to make the slides from the symposium promptly available.
Second, the Duke-Margolis Health Policy Center has recently announced a 14 June 2018 workshop entitled “Understanding the Development Challenges Associated with Emerging Non-Traditional Antibiotics”. Running from 8:30am-5:00pm on that day and supported by a cooperative agreement with FDA, “this public event will focus on the range of non-traditional pharmaceutical approaches being developed to combat bacterial infections. Speakers will address the importance of development in this area, the full spectrum of technologies currently under development, and the outstanding scientific challenges in assessing efficacy of these products in pre-clinical and clinical settings. Discussion will help to prioritize challenge areas in which additional considerations and research will need to be developed moving forward.”
I hope to see you at one or both of these events!
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: http://amr.solutions/blog/
Upcoming meetings of interest to the AMR community:
- 16 Apr 2018 (Washington): Duke-Margolis & FDA event: “Evaluating Inclusion and Exclusion Criteria in Clinical Trials”
- 18-20 Apr 2018 (Portland, OR): SHEA (Society for Healthcare Epidemiology of America)
- 21-24 Apr 2018 (Madrid): ECCMID
- 4-7 Jun 2018 (Boston): BIO (multiple AMR-focused sessions are expected)
- 7-11 Jun 2018 (Atlanta): ASM Microbe
- 14 June 2018 (Washington): Duke-Margolis & FDA event: “Understanding the Development Challenges Associated with Emerging Non-Traditional Antibiotics”
- 22-27 Jul 2018 (Bryant University, Smithfield, RI): Gordon Research Conference on Drug Resistance for Cancer, Infectious Disease and Agriculture
- 4-7 Sep 2018 ESCMID-ASM Conference (#3) on Drug Development for AMR (Lisbon, Portugal)
- 3-7 Oct 2018 (San Francisco): ID Week
- 6-14 Oct 2018 International Course on Antibiotics and Resistance (ICARe, Les Pensières, Annecy, France)