VAX-31 Meets All Primary End Points vs PCV20 and PCV21 in Pivotal Phase 3 OPUS-1 Trial

The investigational 31-valent pneumococcal conjugate vaccine (PCV) candidate VAX-31 (Vaxcyte) met all prespecified primary immunogenicity and safety end points in the pivotal phase 3 OPUS-1 trial (NCT07284654), according to topline results the company announced on October 5, 2026. The results are expected to anchor a planned biologics license application (BLA) to the FDA.¹

Trial Compared VAX-31 With Both Leading Adult PCVs

OPUS-1 is a randomized, double-blind, active-controlled trial that enrolled 4047 participants at approximately 30 US sites. Healthy, pneumococcal-naive adults aged 50 years and older (n = 3572) were randomly assigned 1:1:1 to a single dose of VAX-31; 20-valent PCV (PCV20; Prevnar 20; Pfizer); or 21-valent PCV (PCV21; Capvaxive; Merck). A separate cohort of adults aged 18 to 49 years (n = 475) was randomly assigned 3:1 to VAX-31 or PCV20. Immune responses were measured 1 month after vaccination, and safety is being followed for 6 months.¹

Noninferiority Met Across All Shared Serotypes

Among adults aged 50 years and older, all 28 serotypes of VAX-31 share with PCV20 and/or PCV21 met the prespecified noninferiority criterion, which was defined as a lower bound of the 95% CI (LBCI) for the opsonophagocytic activity geometric mean ratio exceeding 0.667—a threshold more stringent than the historical margin of 0.5. The 3 serotypes unique to VAX-31, along with cross-reactive serotype 20B, met the superiority criterion (LBCI > 2.0).¹

In the immunobridging analysis, VAX-31 met noninferiority for all 32 serotype comparisons in adults aged 18 to 49 years vs those aged 50 to 64 years.¹

In head-to-head comparator analyses, VAX-31 met the 0.667 criterion for all 20 serotypes shared with PCV20, as well as 17 of 19 shared with PCV21. Serotypes 3 and 12F fell short of 0.667 against PCV21 but met the historical 0.5 threshold, which was a prespecified key secondary end point. James Wassil, chief scientific officer and chief operating officer of Vaxcyte, said the company expects the PCV21 comparison to be a particular focus of FDA review, given that serotypes unique to PCV21 account for a larger share of current US adult disease.¹

Safety Comparable to Licensed Vaccines

VAX-31 was well tolerated, with a safety profile similar to PCV20 and PCV21 across all age groups. Solicited reactions were generally mild to moderate, and most resolved within 48 hours. No serious adverse events (AEs) were considered vaccine-related, and no participants discontinued because of AEs.¹

Expanded Adult Recommendations Raise the Stakes

The results arrive as more adults become eligible for pneumococcal vaccination. On October 23, 2024, the CDC's Advisory Committee on Immunization Practices recommended a single PCV dose for all PCV-naive adults aged 50 years and older, aiming to improve prevention in adults aged 50 to 64 years, particularly among demographic groups with higher disease rates.² Current CDC guidance lists PCV15, PCV20, or PCV21 for this population, and individuals who receive PCV20 or PCV21 are considered to have completed their pneumococcal vaccination.³

Serotype coverage remains a key differentiator. A 2025 modeling analysis in The Journal of Infectious Diseases found that coverage and preventable disease burden were lowest for PCV15 and highest for a 31-valent candidate, with PCV21 also targeting a sizable share of adult disease.⁴ Vaxcyte estimates VAX-31 could cover approximately 95% of invasive pneumococcal disease (IPD) and 88% of pneumococcal pneumonia in US adults aged 50 years and older—an incremental 13% to 36% and 19% to 31%, respectively, over current adult PCVs.¹

“Important gaps remain in adult pneumococcal disease coverage,” Luis Jodar, PhD, chief medical officer of Vaxcyte, said in the news release announcing the trial data. Pneumococcal pneumonia alone causes an estimated 225,000 adult hospitalizations in the US annually.¹

Next Steps Toward Licensure

Vaxcyte expects to report results from the OPUS-2 (NCT07365826) and OPUS-3 phase 3 trials in the first half of 2027, followed by a manufacturing consistency study, with a BLA submission planned for the first half of 2028. The FDA previously granted VAX-31 breakthrough therapy designation for IPD prevention, expanding in May 2025 to include pneumococcal pneumonia.¹

VAX-31 remains investigational, and until a new product is licensed and recommended, pharmacists should continue to follow current CDC guidance.³

REFERENCES

1. 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. News release. Vaxcyte, Inc. October 5, 2026. Accessed October 16, 2026. https://investors.vaxcyte.com/news-releases/news-release-details/vaxcyte-reports-positive-topline-data-opus-1-pivotal-adult-phase

2. Kobayashi M, Leidner AJ, Gierke R, et al. Expanded recommendations for use of pneumococcal conjugate vaccines among adults aged ≥50 years: recommendations of the Advisory Committee on Immunization Practices—United States, 2024. MMWR Morb Mortal Wkly Rep. 2025;74(1):1-8. doi:10.15585/mmwr.mm7401a1

3. Pneumococcal vaccine recommendations. CDC. February 25, 2026. Accessed October 16, 2026. https://www.cdc.gov/pneumococcal/hcp/vaccine-recommendations/index.html

4. King LM, Andrejko KL, Kobayashi M, et al. Pneumococcal serotype distribution and coverage of existing and pipeline pneumococcal vaccines. J Infect Dis. 2025;232(4):e609-e620. doi:10.1093/infdis/jiaf376