Alan Carr’s Sep 2019 Antibacterial-Antifungal Update; Pews’ updated pipeline review

Dear All,

First, Alan Carr’s Sep 2019 Antibiotic and Antifungal Update (link) is, as usual, required reading (see also this prior blog). Key highlights:

• He provides an updated by-month sales report from Jan 2016 through Jul 2019 of all products approved since 2009. Sadly, it remains the case that only 4 drugs have sold more than $100m in the 12 months ending Jul 2019 and the maximum for these products is $143m (ceftaroline).
• Approvals of Recarbrio (imipenem-relebactam) and Xenleta (lefamulin) are reviewed
• He predicts that the FY2020 CMS Final Rule (go here for details) will reduce some of the financial pressure on hospitals but will not strongly influence sales. I see his point but would add my personal guess that the new severity codes will encourage greater use of diagnostics and (I hope!) increase use of the right drug.
• Finally, he provides a fascinating analysis of the DISARM legislation introduced this summer.
  • In brief, DISARM would build on the FY2020 CMS FInal Rule by establishing a DRG carve-out for QIDP-designated drugs.
  • Alan analyzes DISARM’s potential impact on the inpatient market by modeling the possibility of physicians using QIDP-designated drugs to replace 50-100% of the use of some older agents.
    • For clarity, note that DRGs apply only to the inpatient setting and hence DISARM will only have an impact on the inpatient market.
  • Importantly, his definition of the older drugs that would be replaced is subtle: he correctly notes that (for example) use of vancomycin is not going to be shifted.
    • Rather the shift to newer drugs would occur in the subset of patients already receiving a more recent (but non-QIDP) drug such as linezolid.
  • Run out over the 10-year period 2020-2029, the net is an incremental growth in market value for QIDP-designated drugs of $8.1b if there is a 50% shift from older to newer drugs. You can of course get higher or lower numbers by varying that % uptake, but I think 50% is a good guess.
  • Translation: If spread out over (say) 10 QIDP-designated drugs, the additional $8.1b in total 10-year sales results in incremental sales of $800m/drug. Again, that’s the total increment over 10 years for each drug.

Overall, this strikes me as a very fair step towards (in aggregate) reimbursing innovators for the $1.3-$1.5b required to bring any given new drug to market and then keep it on the market for 10 years ($1b to get to approval, $0.3-0.5m for post-approval work (e.g., pediatrics), supply chain, pharmacovigilance, surveillance for resistance, etc.)

Relatedly, Pew Trusts have released an updated pipeline analyses for small molecules (link, 42 in development) and non-traditionals (link, 26 in development). Useful related links/documents are:

• Pew’s animated pipeline for 2014-2018 (link). Watch the molecules move forward and backward!
• Pew’s 2-page infographic entitled “The Critical Need for New Antibiotics” (link)
• Two recent in-depth and complementary papers on non-traditional antibiotics (Theuretzbacher and Piddock in Cell Host & Microbe; Rex et al. in Nature Communications; more details on both at this link)

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:

• 10 Sep 2019 (webinar, 17:00-18:30 CEST): REVIVE webinar entitled “Models for antimicrobial R&D: Advanced and complex in vivo models for infectious disease research.” Go here to register.
• 3 Oct 2019 (webinar, 17:00-18:30 CEST): REVIVE webinar entitled “Natural product antibiotics: from traditional screening to novel discovery approaches.” Go here to register.
• 2-6 Oct 2019 (Washington, DC): IDSA’s annual IDWeek meeting.
• 19-27 Oct 2019 (Annecy, France): International Course on Antibiotics and Resistance (ICARe) – A soup-to-nuts intensive residential training program on all things AMR, especially R&D for new antibiotics. See this link for details.
• 7 Nov 2019 (webinar, 17:00-18:30 CEST): REVIVE webinar entitled “Converting Gram-positive-only compounds into broad-spectrum antibiotics.” Go here to register.
• 8 Nov 2019 (London): Launch of “Reviewing Antimicrobial Resistance: Where Are We Now and What Needs to Be Done?”, a follow-up to the UK AMR Review‘s report and recommendations. Go here to register. 
• 19 Nov 2019 (London): BSAC seminar entitled “Into clinical practice: Meeting the challenges of Gram-negative infection management”. A one-day conference on treatments for Gram-negative infections. Go here for details.
• 28-29 Nov 2019 (Birmingham, UK): BSAC workshop entitled “ARM (Antibiotic Resistance & Mechanisms)”. This meeting is a research forum for UK-based researchers at all levels, including PhD students and technicians. Go here for details.
• 16-18 Dec 2019 (Bangkok, Thailand): 3rd International Symposium on Alternatives to Antibiotics in Animal Production. Go here for details: https://www.ars.usda.gov/alternativestoantibiotics/
• 21 Jan 2020 (London): BSAC’s 2nd Antimicrobial Chemotherapy Conference – An ABC for everyone involved in developing new antimicrobials. Go here for details.
• 20 Feb 2020 (London, UK): Westminster Health Forum conference entitled “Antimicrobial resistance – coordinating a global response and progress on the UK strategy.” Go here for details.
• [NEW] 26-27 Feb 2020 (Washington, DC): US PACCARB public meeting. Go here for details.
• 1-6 Mar 2020 (Il Ciocco, Tuscany, Italy): GRC on Antibacterial Discovery and Development: “Now is the time to re-boot antibiotic R&D before it’s too little, too late.” Go here for details.
• 12-13 Mar 2020 (Berlin?): BEAM-, Novo REPAIR-, CARB-X-, DZIF-, ND4BB-, ENABLE-supported (among a long list!) Conference on Novel Antimicrobials and AMR Diagnostics. Final location is TBD, details will appear here, and you should mark your calendar now. 
• 16-17 Mar 2020 (London): BSAC Spring Conference entitled: “Bridging the gap between science, policy and effective antimicrobial use.” Go here for details. 
• 18-21 Apr 2020 (Paris): Annual ECCMID meeting (#30)
• 25-30 May 2020 (Rotterdam), Annual ESPID meeting (European Society for Pediatric ID, #38)
• 10-13 Apr 2021 (Vienna): Annual ECCMID meeting (#31)
• [NEW] 1-4 Sep 2020 (Dublin): Annual ASM-ESCMID Conference on Antibiotic Development #5! Mark your calendar now, details to follow.
• [NEW] 9-10 Sep 2020 (Washington, DC): US PACCARB public meeting. Go here for details.