Addendum: This is the third in a 3-newsletters series on this topic. Go here and here for the prior newsletters.
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:
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.
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!
“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.
