Commissioner Gottleib (New FDA initiatives, need for Pull incentives) + updated Pew pipeline analyses

Dear All: It was a HUGE day at the Pew Charitable Trusts today!

First, Commissioner Scott Gottleib gave a superb and very exciting speech. You can either read or listen to the entire speech. There is also a panel discussion after his talk that is worth replaying. Here are some highlights from Commissioner Gottleib’s talk:

• FDA is working to coordinate all its AMR efforts and part of this is a new integrated website that is effectively a one-stop shop for all FDA AMR-related activities. On this website you can read about …
  • FDA’s new 5-year plan for stewardship in veterinary settings
  • FDA’s public RFI (Request for Information) on development of new antibacterial drugs active against MDR bacteria
  • FDA’s specific focus on 4 topics:
    • Efficient product development
    • Support for antimicrobial stewardship
    • Collecting data on antimicrobial resistance
    • Development of new regulatory tools
  • And much more … you’ll need to look through the entire webpage to understand its impressive scope.

• The RFI (Request for Information) on development of new antibacterial drugs active against MDR bacteria is especially noteworthy and you should consider submitting your thoughts. FDA are interested in suggestions for research in 5 areas:
  1. Evaluate potential innovations in clinical trial design for new antibacterial drugs such as enrollment strategies, data collection streamlining, drug development tools,clinical endpoints, and new statistical analytic approaches.
  2. Advance the science of in vitro, animal model, and/or pharmacokinetic studies to facilitate antibacterial drug development, including studies focused on drug development for special populations such as patients with unmet need, children and patients with renal or hepatic dysfunction.
  3. Evaluate the use of rapid diagnostic tests in clinical trials for new antibacterial drugs to enrich enrollment of patients with the condition of interest.
  4. Advance the science of antibacterial drug susceptibility evaluation.
  5. Evaluate potential endpoints in clinical trials in the area of unmet medical need.

• In his comments, Commissioner Gottleib calls for both Push and Pull incentives:
  • His discussions of Pull incentives were completely on target — he clearly lays out the background issues and rationale.
  • He indicated that FDA and CMS are working together to further develop these ideas.
  • His initial focus is on some form of subscription model to ensure access to new drugs while providing enough of a foundation for a guaranteed market to encourage ongoing work.
  • During the Q&A, he very clearly articulated the principles of paying for new antibiotics using the equivalent of market-entry rewards. 
• I think it is incredibly powerful to have such a clear call for Pull incentives from the FDA
  • Although it is easy to criticize any given set of Pull incentives, the challenge is to propose an alternative that can actually be implemented.
  • The attractive thing to my ear about the ideas from Dr. Gottleib is that the ideas align well with the principles elucidated by DRIVE-AB for solutions that could actually be effectively implemented.
  • And the core advice to those of us doing development is to focus on innovation. I don’t think it will be possible for all new products to be part of the early wave of Pull incentives — successful products will offer something special or distinctive.

Second, Pew Trusts’ antibiotic resistance projecthas updated its pipeline reviews of both the 42 small molecules as well as the 30 non-traditional products (antibodies, vaccines, etc.) currently in clinical development. It’s exciting to see that the pipeline includes a reasonable number of products for Gram-negative bacteria (12) of which at least a few are truly novel products (1 small molecule, 5 non-traditional products). At the same time, these numbers are tiny by comparison to the magnitude of the public threat, as well as being dwarfed by the number of products in development in other areas (e.g., oncology).

On the theme of non-traditional antibiotics, the panel discussion that follows Dr. Gottlieb’s talk is really worth your time. The key messages firmly reinforce those from the 21-22 Aug 2018 FDA workshop on non-traditional products: These products can usually be developed using existing tools and trial designs and those approaches should be followed if at all possible.

Wow! A big day! There’s a lot to review here … you should set aside a couple of hours for a detailed look. And, you’ll want to seriously consider responding to the RFI on new antibacterial drugs for MDR bacteria.

Good work by Team Pew and by FDA! 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: https://13.43.35.2/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.
• BARDA DRIVe’s Solving Sepsis Broad Agency Announcement (BAA-18-100-SOL-00018) is open for applications through 31 May 2019. See also this prior newsletter as well as the FedBizOpps.gov website for general details.

Upcoming meetings of interest to the AMR community:

• 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] 23-26 Sep 2018 (Washington, DC): ASM Conference on Rapid Applied Microbial Next-Generation Sequencing and Bioinformatic Pipelines.
• 24-28 Sep 2018 (Big Sky, Montana): MSG-ERC (Mycoses Study Group) Biennal meeting
• 25 Sep 2018 (New York City): UN General Assembly side-event entitled “Launch of the AMR Challenge.” Sponsored by CDC, BMGF, Pew, Wellcome, and the UN foundation, this is a kick-off event for a year-long effort to encourage commitments to tackling the AMR problem.
• 26 Sep 2018 (Columbus, OH): Opening meeting of PACCARB. The available data about the meeting are found here.
• 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
• 8 Nov 2018 (Alderley Park, UK): Bionow’s 1-day Bioinfect conference
• 13 Nov 2018 (London): All-Parties Parliamentary Working Group on AMR meeting. Online materials here. 
• 16 Nov 2018 (Berlin): Max Planck Institute for Innovation and Competition is organizing a conference on life sciences and innovation. Online materials here.
• 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.