Vaxcyte VAX-31 meets all primary endpoints in pivotal Phase 3 trial
Vaxcyte has reported that VAX-31, its 31-valent pneumococcal conjugate vaccine (PCV) candidate, met all prespecified primary endpoints in OPUS-1, the first of three pivotal adult Phase 3 trials. The results, the company says, will form the cornerstone of a planned Biologics License Application (BLA) submission to the US Food and Drug Administration, targeted for the first half of 2028.
The OPUS-1 trial enrolled 4,047 pneumococcal-naive adults at approximately 30 US sites. The primary cohort comprised adults aged 50 and older (n=3,572), with a separate immunobridging cohort of adults aged 18–49 (n=475). Participants in the older cohort were randomised 1:1:1 to receive VAX-31, Pfizer's Prevnar 20 (PCV20) or Merck's Capvaxive (PCV21); the younger cohort was randomised 3:1 to VAX-31 or PCV20.
Trial results in detail
In adults aged 50 and older, all 28 VAX-31 serotypes shared with PCV20 and/or PCV21 met the prespecified noninferiority criterion, set at a lower bound of the 95% confidence interval (LBCI) greater than 0.667 for opsonophagocytic activity geometric mean ratios. The three serotypes unique to VAX-31, together with cross-reactive serotype 20B, cleared the more demanding superiority threshold of LBCI greater than 2.0. In the immunobridging analysis, VAX-31 met noninferiority across all 32 serotype comparisons in adults aged 18–49 relative to the 50–64 cohort.
Two minor misses emerged in the prespecified individual comparator analysis against PCV21: serotypes 3 and 12F did not reach the LBCI greater than 0.667 noninferiority threshold, though both met the historically accepted LBCI greater than 0.5 standard, which was a prespecified key secondary endpoint. Vaxcyte's chief scientific officer and chief operating officer, James Wassil, noted that the PCV21 comparison is likely to be a focal point for FDA reviewers, given current US epidemiology in which PCV21-specific serotypes account for a disproportionate share of adult disease. On safety, no serious adverse events were attributed to the study vaccines and no participants discontinued due to adverse events.
Vaxcyte positions VAX-31 as offering incremental coverage of 13–36% of invasive pneumococcal disease and 19–31% of pneumococcal pneumonia over currently available adult PCVs, based on CDC 2022–2024 Active Bacterial Core surveillance data and published serotype distribution analyses.
Market context and regulatory path
The adult pneumococcal vaccine market is currently split between Pfizer's PCV20 and Merck's PCV21, both of which reached US approval within the last few years and displaced the older PCV13. A 31-valent candidate that demonstrates noninferiority against both approved products at a more stringent statistical threshold would represent a meaningful commercial and public health step forward, provided FDA is satisfied with the serotype 3 and 12F results against PCV21.
The FDA granted VAX-31 Breakthrough Therapy designation in May 2025, expanded to cover pneumonia prevention as well as invasive disease. That status can accelerate review timelines, though it does not guarantee approval. OPUS-2 and OPUS-3 data are expected in the first half of 2027, to be followed by a manufacturing consistency study before the BLA filing. An infant programme remains in Phase 2, with topline data also anticipated by mid-2027.
Grant Pickering, chief executive and co-founder of Vaxcyte, said the OPUS-1 outcome "sets a new benchmark for the class," adding that the trial inaugurated a more stringent noninferiority standard than prior pivotal PCV studies. The company also holds VAX-24, a 24-valent candidate with positive Phase 2 data in adults and infants, giving it a staged pipeline should VAX-31 encounter regulatory headwinds.
Pneumococcal pneumonia causes an estimated 225,000 adult hospitalisations annually in the United States, and drug-resistant Streptococcus pneumoniae is classified as a serious threat by the CDC, providing a clear public health rationale for broader-spectrum coverage.