FDA workshop on non-traditional antibacterials (21-22 Aug 2018)

 Please be sure to look closely at the events calendar: Q&A with Scott Gottlieb, Lipinski on Lipinski, and more!

Dear All: FDA’s 21-22 Aug 2018 workshop on the development of non-traditional antibacterial agents was an excellent discussion of core challenges in this area. The agenda plus all the meeting materials (including the public comment slides and replays of the webcasts) are available on this web page. There’s a lot here to digest, so let me offer this guided tour:

• In the opening session,
  • Kevin Outterson and I provided an initial overview that discusses the core problem of showing value, the challenges with defining the idea of a Non-Traditional (NT) product, and why this matters to CARB-X.
  • Helen Boucher brought the challenges in the clinic together with the promise of NT products in her discussion of two powerful case vignettes. Any of us could be the patient who needs these products!
  • Owen McMaster provided a summary of key Pharmacology and Toxicology issues — my takeaway here was that the guidelines for NT products were not uniform but you should attempt where possible to apply the usual rules. When this is not possible, well-reasoned adaption is the order of the day.
  • Similarly, Tracey (Xiaohui) Wei discussed Clinical Pharmacology issues with a focus on highlighting some of the unusual ADME and dose-selection issues that may arise, especially with biological products.
  • Kalavati Suvarna rounded out the session by surveying the microbiology issues that arise with NT products.
• The heart of the meeting was then a series of hypothetical but realistic case scenarios:
  • Drug X-1: A monoclonal for preventing VABP (Mary Beth Dorr and Mayurika Ghosh)
  • Drug Z-2: An approach to preventing gut microbiome disruption (and hence C. difficile infection) due to beta-lactam drugs (Michael Kaleko and Ramya Gopinath)
  • Drug Z-3: Reducing the risk of infection due to an MBL-producer by preventing acquisition of same (John Rex)
  • Drug Z-4: A chimeric bacteriophage endolysin as an adjunct for S. aureus infections (Cara Cassino and Ed Weinstein)

My takeaway messages from the day are as listed just below. An expanded slide deck on this topic is found here.

• “Non-Traditional” is a very broad term and requires qualification
  • Sub-dividing into NT Structure vs. Goal (see also the opening Outterson-Rex talk) may help a bit
• Current development tools are often suitable
  • There may be gaps around measures of delayed (indirect) benefit
  • There may be gaps around evaluation of combination products
• The lack of a tool (or path) can be managed
  • New approaches have been / can be developed
• The product’s whole effect must be considered
  • Don’t be seduced by a pretty mechanism
• A high-level guidance document might be useful
  • But we’re not ready to commit to many details

My closing thought is that I think that 10-15 years from now we will view many non-traditional products as “business as usual.” This rather reminds me of the comment that “All Art was once Contemporary.”  If you want to dig a little deeper into the philosophy side, you could even (re)read Thomas Kuhn’s The Structure of Scientific Revolutions in which he discusses the contrast between small incremental changes and significant paradigm shifts. Some of the products we are discussing are incremental, but ideas around products with delayed (indirect, or community-level) benefits could represent a substantial shift in perspective.

Meditatively yours, –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/

General notes of interest for the AMR community

• Novo’s REPAIR Impact fund will re-open for proposals during the window 4 Sep – 11 Oct. Watch for further news here.
• IMI AMR Accelerator programme Pillar A within IMI Call 15: Capability-building network to manage the whole accelerator and strengthen AMR science. This is a two-stage call, with letter of intent from applicants expected on 24 Oct 2018.
• IMI AMR Accelerator programme Pillar B: Tuberculosis drug development network within IMI Call 15: Tuberculosis drug development network to collaboratively progress TB compounds and validate new tools for TB drug development. This is a two-stage call, with letter of intent from applicants expected on 24 Oct 2018.
• IMI Call 16: A series of individual programs where a single EFPIA partner works with a consortium to progress compounds for for TB, non-tuberculous mycobacteria, and Gram-negatives. This is a one-stage call, with full proposal from the EFPIA and applicant consortium expected on 24 Oct 2018.

Upcoming meetings of interest to the AMR community:

• 26-29 Aug 2018 (Atlanta, GA): CDC’s International Conference on Emerging Infectious Diseases (ICEID). Register here.
• [Don’t miss this one!] 4-7 Sep 2018 ESCMID-ASM Conference (#3) on Drug Development for AMR (Lisbon, Portugal). Full program is now posted.
• [NEW] 13 Sep 2018 (webinar): “Beyond the Lipinski Rule of 5“, a CDD-sponsored webinar featuring Dr. Lipinski himself!
• [NEW] 14 Sep 2018 (Washington, Pew Trusts): FDA Commissioner Gottlieb talks about FDA’s plans to combat AMR.
• 17 Sep 2018 (Washington): NIAID workshop entitled “Science and Regulation of Live Microbiome-Based Products Used to Prevent, Treat, or Cure Diseases in Humans.” More details and registration are here.
• [NEW] 26 Sep 2018 (Columbus, OH): Opening meeting of PACCARB. Agenda not yet posted online.
• 24-28 Sep 2018 (Big Sky, Montana): MSG-ERC (Mycoses Study Group) Biennal meeting
• 28 Sep 2018 (New York City): New York Academy of Sciences workshop entitled “Minimizing the Risk of Antimicrobial Resistance from Food Animal Production”
• 3-7 Oct 2018 (San Francisco): ID Week
• 6-14 Oct 2018 International Course on Antibiotics and Resistance (ICARe, Les Pensières, Annecy, France) 
• 23 Oct 2018 (New York City): New York Academy of Sciences workshop entitled “New Therapeutic Strategies to Combat Antibacterial Resistance“
• 26 Oct 2018 (London): EMA information day for SMEs: “Regulatory toolbox for medicines and combined devices developers”. Here is the current agenda. Webcast will be available. More details from sme@ema.europa.eu.
• 29-30 Oct 2018 (Washington: BARDA Industry Days, a 2-day conference on countermeasure development for the US Government
• 7-9 Nov 2018 (Seville, Spain): Better Methods for Clinical Studies in Infectious Diseases and Clinical Microbiology: A Hands-on Workshop
• 13 Nov 2018 (London): All-Parties Parliamentary Working Group on AMR meeting (advance notice, no online details as yet) 
• 16 Nov 2018 (Berlin): Max Planck Institute for Innovation and Competition is organizing a conference on life sciences and innovation. No online details as yet.
• 29-30 Nov 2018 (Birmingham, UK): BSAC (British Society Antimicrobial Chemotherapy): Antibiotic Resistance Mechanisms Workshop for Researchers.
• 14-15 Mar 2019 (Berlin): BEAM– and ND4BB-ENABLE-sponsored Berlin Conference on Novel Antimicrobials and AMR Diagnostics. Details here.
• 21-22 Mar 2019 (Birmingham, UK): BSAC Spring Conference.