Vaxcyte, Inc. (Nasdaq: PCVX) has announced positive topline results from its Phase 1/2 study of VAX-31, a 31-valent pneumococcal conjugate vaccine (PCV) candidate designed to prevent invasive pneumococcal disease (IPD). The study, involving 1,015 healthy adults aged 50 and older, demonstrated that VAX-31 was well-tolerated and induced robust immune responses across all 31 serotypes. Based on these results, Vaxcyte plans to advance VAX-31 to a Phase 3 program for adult indication.
Safety and Tolerability
The Phase 1/2 study revealed that VAX-31 had a safety profile similar to Prevnar 20® (PCV20) at all doses studied over a six-month evaluation period. Commonly reported local and systemic reactions were generally mild to moderate, resolving within days of vaccination, with no significant differences observed across the cohorts. No serious adverse events were attributed to the study vaccines.
Immunogenicity
VAX-31 exhibited robust opsonophagocytic activity (OPA) immune responses for all 31 serotypes at all doses studied. At the middle and high doses, VAX-31 met or exceeded the OPA response non-inferiority criteria for all 20 serotypes common with PCV20. Specifically, at the high dose, average OPA immune responses were greater for 18 of 20 serotypes compared to PCV20 (geometric mean ratio (GMR) greater than 1.0), with seven of these serotypes achieving statistically higher immune responses compared to PCV20. At the middle dose, 13 of 20 serotypes had a GMR greater than 1.0, and five serotypes achieved statistically higher immune responses compared to PCV20. For all 11 incremental serotypes unique to VAX-31, and not in PCV20, all three doses met the superiority criteria.
Clinical and Commercial Strategy
"We believe the positive safety, tolerability and immunogenicity results from the VAX-31 Phase 1/2 study affirm the potential of our site-specific, carrier-sparing platform to deliver the broadest-spectrum PCVs that provide protection against both currently circulating and historically prevalent strains," said Grant Pickering, Chief Executive Officer and Co-Founder of Vaxcyte. The company plans to initiate a pivotal, non-inferiority Phase 3 study by mid-2025 and announce topline data in 2026. The remaining VAX-31 Phase 3 studies are slated to begin in 2025 and 2026, with a Biologics License Application submission contingent on the results.
Study Design
The VAX-31 Phase 1/2 clinical study was a randomized, observer-blind, active-controlled, dose-finding trial. It evaluated the safety, tolerability, and immunogenicity of a single injection of VAX-31 at three dose levels (low, middle, and high) compared to PCV20 in 1,015 healthy adults aged 50 and older. The study included an assessment of antibody responses at Month 1, based on OPA and immunoglobulin G (IgG), at each of the three VAX-31 doses and compared to PCV20 for the 20 serotypes in common, as well as for the additional 11 serotypes contained in VAX-31, but not in PCV20. The study enrolled subjects from 25 sites in the United States.
About Pneumococcal Disease
Pneumococcal disease (PD), caused by Streptococcus pneumoniae bacteria, can lead to invasive pneumococcal disease (IPD), including meningitis and bacteremia, and non-invasive PD, such as pneumonia, otitis media, and sinusitis. In the United States, pneumococcal pneumonia results in approximately 150,000 hospitalizations annually. Streptococcus pneumoniae is a leading cause of vaccine-preventable deaths in children under five globally and causes over 50% of bacterial meningitis cases in the United States. The rise of antibiotic-resistant strains underscores the need for broader-spectrum vaccines.
About VAX-31
VAX-31 is designed to prevent IPD, which is particularly severe in infants, young children, older adults, and those with immune deficiencies or chronic health conditions. It aims to increase coverage to more than 95% of IPD circulating in adults aged 50 and older in the United States, potentially providing an incremental 12-40% coverage over current standard-of-care adult PCVs.
