Vaxcyte VAX-31 meets all Phase 3 primary endpoints in OPUS-1 adult trial
Vaxcyte has reported that VAX-31, its next-generation 31-valent pneumococcal conjugate vaccine (PCV) candidate, met all prespecified co-primary endpoints in the OPUS-1 pivotal Phase 3 trial, clearing a key hurdle on the path to a US Biologics License Application (BLA) filing. The randomised, double-blind, active-controlled study enrolled 4,047 pneumococcal-naïve adults across two age bands: 3,572 participants aged 50 and older, and 475 aged 18 to 49.
The primary immunogenicity analysis compared VAX-31 against two marketed comparators, Pfizer's Prevnar 20 (PCV20) and Merck's Capvaxive (PCV21), using opsonophagocytic activity geometric mean ratios. VAX-31 met noninferiority criteria for all 28 serotypes it shares with either comparator and demonstrated superiority for the three serotypes unique to VAX-31 as well as cross-reactive serotype 20B. No serious adverse events were attributed to the study vaccines, and no participants withdrew because of adverse events.
A nuanced read on two serotypes
One caveat warrants attention. In prespecified head-to-head comparisons against PCV21 alone, VAX-31 did not meet the primary noninferiority threshold of a lower confidence bound above 0.667 for serotypes 3 and 12F, though it did clear a secondary historical threshold of 0.5. Vaxcyte acknowledged that FDA review is likely to focus on the PCV21 comparison, given that the serotypes unique to Capvaxive account for a larger share of adult pneumococcal disease burden in current US epidemiology. The company described this as an expected area of regulatory scrutiny rather than a programme-threatening finding.
Grant Pickering, chief executive and co-founder, said the OPUS-1 results "inaugurated a more stringent noninferiority standard" and that the company remains confident in VAX-31's potential best-in-class profile. Full data are expected to be presented at a medical conference; the release did not name a specific venue or date.
Financing and competitive landscape
Following the OPUS-1 readout, Vaxcyte completed concurrent public offerings in October 2026 raising approximately $1.1 billion in net proceeds through equal tranches of common stock and convertible senior notes, the latter bearing 1.5% interest and maturing in 2032. Pro forma cash, equivalents and investments stand at approximately $3.4 billion, which the company says is sufficient to fund a potential US commercial launch of VAX-31 for adults alongside the ongoing clinical programme.
R&D expenditure reached $270.3 million in the third quarter, up from $209.9 million in the same period of 2025, driven by manufacturing scale-up and Phase 3 trial costs. The net loss for the quarter was $297.1 million.
The adult pneumococcal vaccine market is now one of the most commercially significant in the broader vaccines sector, with Pfizer's PCV20 and Merck's PCV21 having both obtained US approval for adults in recent years. A 31-valent candidate with a broader serotype footprint than either approved product would be competitively differentiated, though payer and formulary positioning will depend heavily on how the FDA evaluates the serotype 3 and 12F data. Vaxcyte expects OPUS-2 and OPUS-3 results in the first half of 2027, with BLA submission targeted for the first half of 2028.
Earlier in the pipeline, VAX-A1, a prophylactic Group A Streptococcus vaccine, is advancing to Stage 2 of its Phase 1 adult study in Australia following a Data Safety Monitoring Board review. Topline Phase 1 data are expected in the second half of 2027. Group A Strep remains a significant unmet need globally, with no licensed vaccine currently available, making VAX-A1 a potentially important long-term asset if early safety and immunogenicity data are encouraging.