Dear All: (18 June addendum: the materials from the meeting are now posted!)
First, planning continues apace for the 14 June Duke-Margolis workshop on non-traditional products. There is now a link for registration, confirmation that the event is going to be webcast, and a draft agenda. Mark your calendar now to attend either in person or via the webcast!
Second, I would like to expand a bit on my very brief 23 Apr 2018 post on the discussion of non-traditional products at the CARB-X– and GARDP-sponsored ECCMID symposium on regulatory issues. The full talk can be found here and was based on conversations with multiple colleagues (see list on slide 4). The key ideas are:
1. “Non-traditional” covers a lot of territory and it is helpful to refine the idea by envisioning a continuum for antimicrobial therapeutic products that runs from Fleming to non-Fleming products:
- Fleming: A product that 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). Importantly, this means that standard non-inferiority trial designs can be used as the basis for registration.
- Non-Fleming = Everything else = Non-traditional. This can include phage, antibodies, small molecules, large molecules, microbiome … it’s non-Fleming because it lacks one or more of the spectrum-syndrome-speed-standalone properties of a Fleming .
2. Digging more deeply, it then becomes helpful to replace the ambiguous terms alternative to antibiotics, potentiator, and enhancer with four functional archetypes for the non-Fleming therapeutic products: Create, Transform, Enhance, and Restore:
To emphasize, this taxonomy of non-Fleming antimicrobial products is entirely functional: physical nature of the product (large, small, phage, etc.) is not relevant! Rather, the behavior of the product defines the opportunities it brings and the challenges it faces. You should review the entire talk, but here’s a quick summary:
- The archetypes Create and Enhance have the advantage of often being really novel, but the challenges of often being narrow, not standalone, requiring superiority study designs, and not being able to use an MIC as the basis for PK-PD thinking.
- Conversely, the archetypes Transform and Restore have the advantages of leveraging a known component, of being able to leverage an MIC for PK-PD, and often being suitable for standalone development despite the challenge of sometimes being very narrow in terms of spectrum.
3. Agents for prevention are a distinct category and the Fleming/Non-Fleming idea is really not relevant. Instead, the problem is the general challenge of showing an advantage over best Standard of Care. See the slide deck for a specific example.
OK, that’s enough for now … I look forward to the conversation on 14 June where we will hopefully expand further on the challenges around non-traditional products!
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:
- 4-7 Jun 2018 (Boston): BIO (multiple AMR-focused sessions are expected)
- 7-11 Jun 2018 (Atlanta): ASM Microbe
- 12-13 Jun 2018 (Washington): National Academies of Science workshop: Understanding the Economics of Microbial Threats
- [UPDATED] 14 June 2018 (Washington): Duke-Margolis & FDA event: (link to register) “Understanding the Development Challenges Associated with Emerging Non-Traditional Antibiotics”
- 21-22 Jun 2018 (I presume London but don’t know for sure, announcement is pending): joint EMA-FDA-PMDA workshop on pediatric development of antibacterial agents.
- 22-27 Jul 2018 (Bryant University, Smithfield, RI): Gordon Research Conference on Drug Resistance for Cancer, Infectious Disease and Agriculture
- 21-22 Aug 2018 (Rockville, MD): NIAID-NINDS-DTRA workshop entitled “Infectious Disease in The CNS and Therapeutic Strategies to Cross the Blood-Brain Barrier”
- 4-7 Sep 2018 ESCMID-ASM Conference (#3) on Drug Development for AMR (Lisbon, Portugal)
- 24-28 Sep 2018 (Big Sky, Montana): MSG-ERC (Mycoses Study Group) Biennal meeting
- 3-7 Oct 2018 (San Francisco): ID Week
- 6-14 Oct 2018 International Course on Antibiotics and Resistance (ICARe, Les Pensières, Annecy, France)