Ouch! Pfizer terminates S. aureus vaccine trial due futility (Part 3 of 3)

Addendum: This is the third in a 3-newsletters series on this topic. I need to do a specific newsletter on the challenges of vaccines but for now this is the place where I am accumulating relevant papers.

  • Go here and here for the prior newsletters. 
  • 5 Feb 2023 addendum: A GSK Staphylococcus aureus vaccine candidate (GSK3878858A) was reported in GSK’s end-2024 pipeline update as “Not progressing following futility analysis.” This intriguing 4-component vaccine was being studied in a 632-subject Phase I/II study (NCT04420221). Sigh … a very tough area!
  • 15 July 2023 addendum: The results of Pfizer’s STRIVE trial have been published as Hassanzadeh et al. in Clinical Infectious Diseases (2023;77:312-20, https://doi.org/10.1093/cid/ciad218). 
  • With the Hassanzadeh et al. paper, there is also an accompanying editorial (Proctor RA, https://doi.org/10.1093/cid/ciad217) that provides an excellent discussion of the complexity of the S. aureus-human immune system-human microbiome interaction and why this has made vaccine development so hard.

Dear All:

Per a press release today:

  • Pfizer Inc. (NYSE:PFE) announced today that the Phase 2b trial STRIVE (STaphylococcus aureus SuRgical Inpatient Vaccine Efficacy) evaluating the company’s investigational Staphylococcus aureus (S. aureus) multi-antigen vaccine (PF-06290510) is being discontinued due to futility. This decision is based on a recommendation from an independent Data Monitoring Committee (DMC), composed of external experts, after conducting a pre-planned interim analysis.
  • The DMC concluded from these data that the study reached futility, meaning that there is low statistical probability for the study to meet the pre-defined primary efficacy objective in adults undergoing elective spinal fusion surgery after completing a planned Phase 3 expansion of the study.
  • A safety review by the DMC indicated that the investigational vaccine has been safe and well tolerated. STRIVE trial participants who are enrolled in the study will complete the study’s follow-up evaluations.
  • Pfizer is evaluating next steps for the potential development of a S. aureus vaccine

I am so sorry to read this … I had thought this a very strong effort. Details are limited but as a “safety review by the DMC indicated that the investigational vaccine has been safe and well tolerated,” the problem must have been that it was not going to be possible show a reduced infection rate over placebo.

Recall that this vaccine was the subject of a 7 Nov 2017 FDA VRBPAC meeting during which questions about whether (and how) such a vaccine could be developed for general use (go here for the materials from that meeting). As a reminder,

  • Pfizer identified elective open, posterior approach, multilevel, instrumented, spinal fusion surgery (read that carefully) might have a sufficiently high rate of post-operative infections (estimated at 1.44%) despite best prevention methods that the effect of a vaccine could be measured by studying (only!) 3000-6000 subjects.
  • By contrast, a study in another elective orthopedic surgical population (e.g., hip arthroplasty) similar in design to STRIVE would take >10 years to complete and would require enrollment of 20,000 to 40,000 subjects.
  • The AC thus focused on the question of whether (how) the results from one trial could generalize to other settings.
  • I’ll also remind you of the recent Wellcome-sponsored report on antibacterial R&D opportunities which placed a S. aureus vaccine at the mid-point of difficulty:

Picture

Deep sigh … we always knew vaccines were hard but something for S. aureus would be so valuable. There have been multiple prior failed efforts (Fowler & Proctor, CMI 2014) to create such a vaccine and Team Pfizer should be congratulated for giving this another serious try. I hope they will soon share their analyses on why this vaccine failed so that other work can be guided by their efforts. 

 

“My strength lies solely in my tenacity.” Louis Pasteur

Onward! 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:

  • 15 Jan 2018 (London): BSAC’s Antimicrobial Chemotherapy Conference 2019: “An ABC for everyone involved in developing new antimicrobials.” Details here.
  • 29 Jan 2018 (REVIVE webinar): “Clinical development for non-developers Part 3: 
    Antibacterial Drug Enhancer Combinations and Non-traditional Products.” Register here.
  • 4-5 Feb 2019 (London): Hamied Foundation UK-India Antimicrobial Resistance Meeting 2019. This is a 2-day meeting focused on building research links between the UK and India with the specific aim of jointly addressing the challenge of AMR. Register here.
  • 14-15 Mar 2019 (Berlin): BEAM-, CARB-X-, and ND4BB-ENABLE-sponsored Berlin Conference on Novel Antimicrobials and AMR Diagnostics. Details here.
  • 21-22 Mar 2019 (Birmingham, UK): BSAC Spring Conference.
  • 26 Mar 2019 (London, UK): Sponsored by The Economist, a 1-day symposium entitled “Antimicrobial Resistance: Preventing an antibiotic apocalypse.” Register here.
  • 13-16 Apr 2019 (Amsterdam): Annual ECCMID meeting.
  • 24-26 Apr 2019 (Boston): Annual SHEA (Soc. for Hospital Epidemiology of America) Spring meeting
  • 6-11 May 2019 (Ljubljana, Slovenia): 37th Annual Meeting of the European Society for Paediatric Infectious Diseases (ESPID). Details here.
  • 3-6 Jun 2019 (Philadelphia): Annual BIO meeting
  • 20-24 June 2019 (San Francisco): Annual ASM Microbe meeting.
  • [Mark your calendar now!] 3-6 Sep 2019 (Boston). Annual ASM-ESCMID Conference on Antibiotic Development. The Bootcamp series will continue on 3 Sep with the main meeting on 4-6 Sep. Mark your calendar now and check back here for details.
  • 6-8 Sep 2019 (Bilbao, Spain): 5th ESCMID conference on Vaccines. Check back here for details.
  • 2-6 Oct 2018 (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.

Dear All,
 
The IDWeek 2024 program committee is again seeking programs on novel antimicrobial agents and novel diagnostics for presentation in pipeline sessions! Here’s what is sought:

  • “Industry partners are invited to submit antimicrobials that are in preclinical stages of development (Phase II and III preferred) or recently approved after January 2024.
  • “The pipeline sessions will include antibacterials, antifungals, and antivirals (excluding COVID-19 and HIV).
  • “The committee also invites companies developing novel diagnostic technologies with a minimum of some preliminary proof of concept data to submit.” 

This is a great opportunity to tell the story of your development project! The deadline to submit is Wednesday, June 26 via the application portal. Any questions should be directed to program@idsociety.org. Please share this email with anyone you think might be interested in applying!
 
In addition, I’ll also note that those with a more general story to tell should look at the BugHub Stage (and the Global BugHub stage). Both BugHub variants seek “presentations that touch on your experience of working in infectious diseases and presentations that ultimately lead to a greater understanding of our diverse field” via a TED Talk-esque speech about your work. The deadline for applications is 26 June, the same as for the pipeline sessions.

I look forward to seeing you there! All best wishes, –jr

John H. Rex, MD | Chief Medical Officer, F2G Ltd. | Operating Partner, Advent Life Sciences. Follow me on Twitter: @JohnRex_NewAbx. See past newsletters and subscribe for the future: https://amr.solutions/blog/. All opinions are my own.

John’s Top Recurring Meetings

Virtual meetings are easy to attend, but regular attendance at annual in-person events is the key to building your network and gaining deeper insight. My personal favorites for such in-person meetings are below. Of particular value for developers are the AMR Conference and the ASM-ESCMID conference. Hope to see you there!

  • 27-30 April 2024 (Barcelona, Spain): 34th ECCMID, the annual meeting of the European Society for Clinical Microbiology and Infectious Diseases. Go here for details. 
  • 17-20 Sep 2024 (Porto, Portugal): ASM/ESCMID Joint Conference on Drug Development to Meet the Challenge of Antimicrobial Resistance. Go here for the meeting’s general website. You can’t register (yet) for the 2024 event, but save the date!
  • 16-20 Oct 2024 (Los Angeles, USA): IDWeek 2024, the annual meeting of the Infectious Diseases Society of America. Save the date! More details to come!
  • 25-26 February 2025 (Basel, Switzerland): The 9th AMR Conference 2025. Go here to register

Upcoming meetings of interest to the AMR community:

  • [NEW]  9 Apr 2024 (virtual, 830a-10a ET): GARDP’s next REVIVE webinar entitled “Progressing a discovery project – Criteria and challenges.” Register here.
  • [NEW] 9 Apr 2024 (virtual, 10a-1130a ET): CDC webinar “Impacts of Antimicrobial Resistance on Cancer Care.” Click here for details and to register.
  • 10-11 Apr 2024 (virtual): Sepsis Alliance AMR Conference, a 2-day conference focused on “Practical technologies to manage sepsis and counteract the expanding challenge of antimicrobial resistance.” Go here for details and to register.
  • 26 Apr 2024 (Barcelona, Spain): ESCMID workshop entitled “Using Data Science and Machine Learning for Infection Science: A Hands-on Introduction.” Click here to register or here for more details. 
  • 27-30 April 2024 (Barcelona, Spain): 34th ECCMID, the annual meeting of the European Society for Clinical Microbiology and Infectious Diseases. See Recurring Meetings list, above.
  • 26-31 May 2024 (Montreal, Canada): EDAR7, the McGill AMR Centre’s 7th edition of their Environmental Dimension of Antimicrobial Resistance conference. Go here for details; final abstract deadline is 21 Dec 2023.
  • 28-29 May 2024 (in person, Uppsala, Sweden): Uppsala Antibiotic Days, a broad-ranging 2-day program hosted by the Uppsala Antibiotic Center. Go here for details and to register.
  • [NEW] 30-31 May 2024 (face-to-face in Rockville, Maryland as well as online, 8.30-5.30p ET on 30 May, 9-2.40p on 31 May): NIAID-sponsored workshop entitled “Towards realizing the promise of adjunctive immune therapy for invasive fungal infections”. The agenda covers host immunity to invasive fungal infections, immune modulators in the context of fungal infections; and strategies for testing immune modulators as adjunctive therapy. Go here for more details and to register.
  • 9-13 June 2024 (in person, Ascona, Switzerland): “New Approaches to Combat Antibiotic-Resistant Bacteria, 2nd Edition” is a Sunday-Thursday residential workshop focused on the deep biology of AMR. Sponsored by NCCR AntiResist (a Swiss National Science Foundation consortium), the scientific program has the feel of a Gordon Conference. Space is limited, so you are encouraged to apply promptly — go here for details.
  • 13-17 June 2024 (Atlanta, Georgia): ASM Microbe, the annual meeting of the American Society for Microbiology. You can’t register yet, but you can go here for general details.
  • 17-20 Sep 2024 (Porto, Portugal): ASM/ESCMID Joint Conference on Drug Development to Meet the Challenge of Antimicrobial Resistance. See Recurring Meetings list, above.
  • 16-20 Oct 2024 (Los Angeles, USA): IDWeek 2024, the annual meeting of the Infectious Diseases Society of America. See Recurring Meetings list, above. 
  • 19-27 Oct 2024 (Annecy, France, residential in-person program): ICARe (Interdisciplinary Course on Antibiotics and Resistance). Now in its 8th year, Patrice Courvalin directs the program with the support of an all-star scientific committee and faculty. The resulting soup-to-nuts training covers all aspects of antimicrobials, is very intense, and routinely gets rave reviews! Seating is limited, so mark your calendars now if you are interested. Applications open in March 2024 — go here for more details.
  • 4-5 Dec 2024 (in person, Washington, DC): “Fungal Dx 2024: Fungal Diagnostics in Clinical Practice” is a 2-day in-person workshop organized by ISHAM‘s Fungal Diagnostics Working Group. The program and registration links are available at https://fungaldx.com/; the agenda is comprehensive and features an all-star global list of speakers.

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