Vaxcyte reports positive Phase 3 OPUS-1 results for VAX-31, with noninferior immune responses across shared serotypes and favorable safety.
Written By: Anshu Gupta, PharmD
Reviewed By: Pharmacally Editorial Team
Vaxcyte announced on October 5, 2026, that VAX-31 met all prespecified primary endpoints across the age groups studied. The candidate is being developed to prevent invasive pneumococcal disease (IPD) and pneumococcal pneumonia. The OPUS-1 results are expected to form a cornerstone of the company’s planned Biologics License Application (BLA), which will remain subject to review by the U.S. Food and Drug Administration (FDA).
OPUS-1 Phase 3 Trial
OPUS-1 (NCT07284654) was a randomized, double-blind, active-controlled Phase 3 trial evaluating the safety, tolerability and immunogenicity of the VAX-31 High Dose formulation in healthy, pneumococcal-naïve U.S. adults aged 50 years and older, with a separate cohort of adults aged 18–49 years.
The trial dosed 4,047 participants at approximately 30 sites across the United States. Of these, 3,572 participants were aged 50 years and older and 475 were aged 18–49 years.
Participants aged 50 years and older were randomized in a 1:1:1 ratio to receive a single dose of VAX-31, Prevnar 20 (PCV20) or Capvaxive (PCV21). Participants aged 18–49 years were randomized in a 3:1 ratio to receive VAX-31 or PCV20, with PCV20 serving as the safety comparator.
Immune responses were assessed one month after vaccination, while safety and tolerability were evaluated for six months.
VAX-31 Met Primary Immunogenicity Endpoints in Adults Aged 50 Years and Older
VAX-31 met its prespecified co-primary immunogenicity endpoints in adults aged 50 years and older.
All 28 VAX-31 serotypes shared with PCV20 and/or PCV21 met the prespecified noninferiority criterion, based on an opsonophagocytic activity (OPA) geometric mean ratio (GMR) with the lower bound of the 95% confidence interval (LBCI) greater than 0.667.
Among the 11 serotypes shared by VAX-31, PCV20 and PCV21, all 11 met the noninferiority criterion. The nine serotypes shared by VAX-31 and PCV20 but not PCV21 also met the criterion, as did all eight serotypes shared by VAX-31 and PCV21 but not PCV20.
The three serotypes unique to VAX-31 and cross-reactive serotype 20B met the prespecified superiority criterion, with the LBCI exceeding 2.0.
Immunobridging Results in Younger Adults
VAX-31 also met the prespecified primary immunobridging endpoint in adults aged 18–49 years.
Across all 32 serotype comparisons with adults aged 50–64 years, VAX-31 met the noninferiority criterion of an LBCI greater than 0.667.
In comparator analyses, VAX-31 met the prespecified noninferiority criterion for all 20 of the 20 serotypes shared with PCV20. Against PCV21, 17 of 19 shared serotypes met the same threshold.
Serotypes 3 and 12F did not meet the stricter LBCI greater than 0.667 criterion in the individual PCV21 comparison. However, their LBCIs exceeded 0.5, meeting the historical noninferiority threshold prespecified as a key secondary endpoint. Using this historical threshold, VAX-31 met the noninferiority criterion for all 19 serotypes shared with PCV21.
Safety and Tolerability
Vaxcyte reported that VAX-31 was well tolerated, with a safety profile similar to PCV20 and PCV21 across the studied age groups.
Frequently reported solicited local and systemic reactions recorded from Day 1 through Day 7 were generally mild to moderate, with most resolving within 48 hours. The company reported no meaningful differences across the study cohorts.
No serious adverse events were considered related to the study vaccines, and no participants discontinued the study because of adverse events.
Next Development Milestones
Vaxcyte expects to report results from the OPUS-2 and OPUS-3 adult Phase 3 trials in the first half of 2027. These results are expected to support the company’s planned BLA submission for VAX-31 in the first half of 2028.
The company also expects to report topline results from a VAX-31 infant Phase 2 randomized, dose-finding study by the end of the first half of 2027.
The OPUS-1 results provide clinical evidence supporting continued development of VAX-31, particularly its broader serotype coverage and immune responses compared with currently used adult pneumococcal conjugate vaccines. However, the findings are topline company-reported results, and the planned BLA will remain subject to FDA review.
Reference
Vaxcyte Reports Positive Topline Data from OPUS-1, the Pivotal Adult Phase 3 Trial of VAX-31, the Company’s 31-Valent Pneumococcal Conjugate Vaccine Candidate, Vaxcyte, 05 October 2026
Safety, Tolerability, and Immunogenicity of VAX-31 in adults ≥50 Years with Immunobridging to Adults 18-49, ClinicalTrials.gov ID NCT07284654
About the Writer
Anshu Gupta (LinkedIn) is a PharmD professional and healthcare writer with interests in clinical research, pharmacovigilance, regulatory affairs, and medical writing. She has presented research at academic conferences and completed certifications in Good Clinical Practice (GCP), ICH-GCP, and drug safety. Passionate about clinical trials and evidence-based medicine, she is committed to translating scientific evidence into accurate, reliable, and accessible healthcare content.