Vaxcyte Initiates Phase 3 Trial for VAX-31 Pneumococcal Vaccine with Potential to Expand Disease Coverage by 34%
Key Insights
Vaxcyte has dosed the first participants in its OPUS Phase 3 pivotal trial evaluating VAX-31, a 31-valent pneumococcal conjugate vaccine designed to prevent invasive pneumococcal disease and pneumonia in adults.
The trial will enroll approximately 4,000 participants and compare VAX-31 head-to-head with current standard-of-care vaccines Capvaxive (PCV21) and Prevnar 20 (PCV20) in terms of safety, tolerability, and immunogenicity.
VAX-31 is designed to provide 14-34% broader coverage for invasive pneumococcal disease and 19-31% broader coverage for pneumococcal pneumonia compared to existing vaccines in U.S. adults aged 50 and older.
Vaxcyte has initiated dosing in its pivotal Phase 3 OPUS trial evaluating VAX-31, a next-generation pneumococcal conjugate vaccine that could significantly expand disease coverage compared to current standard-of-care vaccines. The randomized, double-blind, active-controlled trial is designed to enroll approximately 4,000 participants and will directly compare VAX-31 with Capvaxive (PCV21) and Prevnar 20 (PCV20) in adults.
The trial design was finalized in consultation and alignment with the U.S. Food and Drug Administration, with topline safety, tolerability and immunogenicity results expected in the fourth quarter of 2026. These results are anticipated to serve as the cornerstone of the VAX-31 Biologics License Application.
Expanded Disease Coverage Potential
VAX-31 is designed to cover approximately 95% of invasive pneumococcal disease (IPD) and approximately 88% of pneumococcal pneumonia in U.S. adults aged 50 and older. This represents a potential 14-34% increase in IPD coverage and 19-31% increase in pneumococcal pneumonia coverage over current standard-of-care vaccines.
"VAX-31 has the potential to provide a 14-34% increase in coverage for IPD and a 19-31% increase in coverage for pneumococcal pneumonia over current standard-of-care vaccines for U.S. adults," said Grant Pickering, Chief Executive Officer and Co-founder of Vaxcyte. "Through this program, we are aiming to expand the breadth of disease and serotype coverage while ensuring immunogenicity levels remain high to ensure durable protection."
The vaccine candidate includes 31 serotypes, with three serotypes (2, 7C, and 20C) unique to VAX-31 compared to existing vaccines. It also maintains coverage of 28 serotypes shared with either or both comparator vaccines.
Trial Design and Endpoints
The OPUS trial is being conducted at approximately 50 sites across the United States. Adults aged 50 years and older (approximately 3,560 participants) will be randomized 1:1:1 to receive a single dose of VAX-31, PCV21, or PCV20. A separate cohort of adults aged 18-49 years (approximately 440 participants) will be randomized 3:1 to receive VAX-31 or PCV20.
The primary immunogenicity objectives include demonstrating noninferiority of VAX-31 compared with PCV21 and/or PCV20 for the 28 shared serotypes, with the criterion that the lower bound of the two-sided 95% confidence interval of the opsonophagocytic activity geometric mean ratio exceeds 0.667. The trial also aims to demonstrate superiority for the three serotypes unique to VAX-31 and serotype 20B, with the lower bound of the 95% confidence interval exceeding 2.0.
Safety and tolerability will be assessed for six months following initial vaccination, with immunogenicity analyses occurring one month post-vaccination.
Building on Previous Success
The Phase 3 program builds on results from Vaxcyte's VAX-31 adult Phase 1/2 study, which demonstrated both broader serotype coverage and stronger overall immune responses than Prevnar 20. In that study, the VAX-31 High Dose was well tolerated with a safety profile similar to PCV20, and all 11 incremental serotypes unique to VAX-31 met superiority criteria. The vaccine delivered greater average immune responses for 18 of the 20 serotypes in common with PCV20, with seven achieving statistically higher immune responses.
Based on these positive results, the FDA expanded the Breakthrough Therapy designation for VAX-31 in May 2025 to include prevention of pneumonia caused by Streptococcus pneumoniae in addition to prevention of IPD in adults.
Addressing Unmet Medical Need
Pneumococcal disease remains a significant vaccine-preventable threat in adults, with pneumococcal pneumonia estimated to result in over 150,000 hospitalizations annually in the United States. Streptococcus pneumoniae is among the World Health Organization's top antibiotic-resistant pathogens requiring urgent attention, and the U.S. CDC lists drug-resistant Streptococcus pneumoniae as a "serious threat."
"Pneumococcal disease remains one of the most significant vaccine-preventable threats in adults, with a growing prevalence of disease from serotypes not covered by existing vaccines," said Jim Wassil, Executive Vice President and Chief Operating Officer of Vaxcyte. "Our next-generation VAX-31 PCV is intended to provide the broadest coverage by maintaining critical pressure on both currently circulating as well as long-established, historically disease-causing serotypes."
Development Timeline
Vaxcyte expects to announce topline data from the OPUS noninferiority trial in the fourth quarter of 2026 and initiate additional Phase 3 studies in 2026 with results expected in 2027. The company plans to generate post-licensure real-world evidence in the adult population following potential approval.
The company is also advancing VAX-31 in pediatric populations, with topline safety, tolerability and immunogenicity data from the infant Phase 2 randomized, dose-finding study expected by the end of the first half of 2027.