Vaxcyte Posts Phase 3 VAX-31 Win Against Prevnar 20 And Capvaxive, Setting Up A 2028 FDA Filing

Vaxcyte reported phase 3 data showing its 31-valent pneumococcal conjugate vaccine candidate VAX-31 held its own against Pfizer’s Prevnar 20 and Merck & Co.’s Capvaxive, a result that pushed the company’s stock up 57% in pre-market trading Monday to $88.50 from a Friday close of $56.48.

The late-stage Opus-1 trial evaluated VAX-31 for prevention of invasive pneumococcal disease and pneumococcal pneumonia in adults. According to Vaxcyte, the candidate met all prespecified primary immunogenicity endpoints across all age groups studied, giving the company what CEO Grant Pickering called the “clinical cornerstone” for an FDA approval application expected in the first half of 2028.

The Data

VAX-31 showed non-inferiority on all 20 pneumococcal strains targeted by Prevnar 20 and on 17 of the 19 serotypes targeted by Capvaxive. In this trial, non-inferiority meant the lower bound of the 95% confidence interval exceeded 0.667.

The two serotypes where VAX-31 missed that criterion against Capvaxive were 3 and 12F. Vaxcyte said those comparisons still met the lower historical non-inferiority threshold of a lower bound of the 95% confidence interval exceeding 0.5.

The safety profile was also part of the readout’s importance. Vaxcyte said VAX-31 was well tolerated and showed safety similar to Prevnar 20 and Capvaxive across all ages studied. That matters because adult pneumococcal vaccination is already an established market, so a challenger needs not only broader valency but also a clean enough profile to support switching.

The Competitive Picture

The commercial argument for VAX-31 rests on trying to reduce the coverage tradeoffs between currently marketed adult PCVs. Vaxcyte chief medical officer Luis Jodar said today’s vaccines differ in the serotypes they cover, forcing choices between currently circulating disease-causing serotypes and historically important ones.

Vaxcyte’s chief scientific officer and chief operating officer James Wassil said the serotypes unique to Capvaxive account for a larger share of pneumococcal disease and pneumococcal pneumonia in U.S. adults, making the VAX-31 versus Capvaxive comparison a likely focus of the FDA review. He also said Prevnar 20 remains an important comparator, including for serotypes 4 and 19F, which are not in Capvaxive. Serotype 4, he noted, has been considered important for health equity because it most often affects certain underrepresented populations.

Jodar said VAX-31 is designed to combine both priorities in a single 31-valent vaccine, with the potential to provide incremental coverage of 13% to 36% of invasive pneumococcal disease and 19% to 31% of pneumococcal pneumonia compared with currently available adult PCVs.

What Comes Next

Vaxcyte is running two more phase 3 adult studies, Opus-2 and Opus-3, with readouts penciled in for the first half of next year. Around that time, the company also plans to report phase 2 data in infants.

The deeper signal in Opus-1 is that Vaxcyte did not have to trade away core comparator performance to reach 31 serotypes. Earlier-stage data in 2024 had surprised some analysts because adding extra immunogen was expected to weaken antibody responses for some serotypes. Vaxcyte attributes its ability to include 31 serotypes to a proprietary carrier-sparing technology designed to preserve exposure of essential T-cell epitopes during conjugation.