Vaxcyte’s VAX-31 Hits Phase 3 Trial Goals

Vaxcyte (PCVX) announced topline results from OPUS-1, a randomized, double-blind, active-controlled Phase 3 trial of its 31-valent pneumococcal conjugate vaccine candidate VAX-31 in adults. The study evaluated the high-dose adult formulation against established pneumococcal conjugate vaccines Prevnar 20 (PCV20) and Capvaxive (PCV21). VAX-31 met all prespecified primary immunogenicity endpoints, positioning OPUS-1 as a pivotal data set in the vaccine’s late-stage development program.

The trial assessed immunogenicity using opsonophagocytic activity geometric mean ratio (OPA GMR) metrics across multiple pneumococcal serotypes. Performance was measured against predefined statistical criteria for noninferiority and, for selected serotypes, superiority, relative to comparator vaccines and historical thresholds.

In adults aged 50 and older, all 28 VAX-31 serotypes shared with PCV20 and/or PCV21 met the prespecified noninferiority criterion, defined as a lower bound of the 95% confidence interval greater than 0.667 for OPA GMR. This indicates that for these shared serotypes, immune responses were not statistically inferior to those generated by the comparator vaccines under the study’s parameters.

For the three serotypes unique to VAX-31 and the cross-reactive serotype 20B, the vaccine met a prespecified OPA GMR superiority criterion with a lower bound confidence interval above 2.0, following a multiplicity adjustment. These findings support the candidate’s ability to extend serotype coverage while maintaining robust immune responses.

A primary immunobridging endpoint evaluated adults aged 18-49 compared with adults aged 50-64. Across all 32 serotype OPA GMR comparisons in this analysis, VAX-31 met noninferiority with a lower bound confidence interval above 0.667, supporting consistency of immune responses in younger adult age groups.

In prespecified individual comparator analyses, VAX-31 met the noninferiority criterion for all 20 of 20 serotypes shared with PCV20. Against PCV21, the vaccine achieved noninferiority for 17 of 19 shared serotypes using the same OPA GMR threshold.

For serotypes 3 and 12F versus PCV21, VAX-31 did not meet the stricter noninferiority threshold of a lower bound confidence interval above 0.667. However, responses for these serotypes met a predefined historical threshold with a lower bound above 0.5, providing additional context for interpreting immunogenicity performance across the full serotype panel.

The prespecified primary safety endpoint showed that VAX-31 was well tolerated, with an overall safety profile similar to PCV20 and PCV21 across all ages studied. No serious adverse events were considered related to any study vaccine, and no participants discontinued the study due to adverse events.

Frequently reported solicited local and systemic reactions during days 1 to 7 after vaccination were generally mild-to-moderate in intensity. Most of these reactions resolved within 48 hours, aligning the tolerability of VAX-31 with that of the comparator pneumococcal conjugate vaccines.

OPUS-1 is designed as a cornerstone trial for the VAX-31 adult program and is expected to underpin a planned Biologics License Application. Vaxcyte (PCVX) plans to present the topline data from this study via a webcast and conference call, providing more detailed results and analysis.

The company anticipates additional adult Phase 3 data from the OPUS-2 and OPUS-3 trials in the first half of 2027. These results are expected to support a targeted Biologics License Application submission for VAX-31 in the first half of 2028, marking the next regulatory milestone in the development of this 31-valent pneumococcal conjugate vaccine candidate.