Vaxcyte's 31-Valent Pneumococcal Vaccine Meets Primary Goals in Phase 3 OPUS-1 Trial

Vaxcyte said on October 5 that its 31-valent pneumococcal conjugate vaccine candidate, VAX-31, met all prespecified primary endpoints in OPUS-1, the pivotal Phase 3 trial in adults that the company plans to use as the basis of a Biologics License Application to the U.S. Food and Drug Administration. The results are topline data reported by the company and have not yet been presented at a medical meeting or published.

Pneumococcal disease is caused by the bacterium Streptococcus pneumoniae, which exists as many different serotypes. Adult conjugate vaccines currently on the U.S. market cover different subsets of those serotypes. VAX-31 is designed to cover 31 of them in a single shot, and Vaxcyte describes it as the broadest-spectrum pneumococcal conjugate vaccine candidate in clinical development, as reported by RTTNews.

Trial design and results

OPUS-1 enrolled more than 4,000 adults in the United States, according to RTTNews' account of the company's announcement. Participants aged 50 and older were randomized to receive VAX-31, Pfizer's Prevnar 20 (PCV20) or Merck's Capvaxive (PCV21). A separate cohort of adults aged 18 to 49 received VAX-31 or PCV20.

The trial measured immune responses rather than rates of disease. According to the company, all 28 serotypes that VAX-31 shares with PCV20 and PCV21 met the prespecified noninferiority criteria, and the three serotypes unique to VAX-31, along with cross-reactive serotype 20B, met superiority criteria. VAX-31 also met the trial's primary immunobridging endpoint, showing noninferior immune responses across all 31 serotype comparisons in adults aged 18 to 49 versus adults aged 50 to 64.

In head-to-head comparisons, VAX-31 met noninferiority criteria for all 20 serotypes it shares with PCV20 and for 17 of the 19 it shares with PCV21. Two serotypes, 3 and 12F, narrowly missed the noninferiority threshold against PCV21 but met a historical regulatory benchmark used in earlier pneumococcal vaccine evaluations, RTTNews reported. Pharmaphorum likewise described slightly lower responses against two Capvaxive-covered strains under a more stringent statistical comparison.

Vaxcyte said the vaccine was well tolerated, with a safety profile similar to PCV20 and PCV21. Most reported reactions were mild to moderate and resolved within a few days. No serious adverse events were considered related to the study vaccine, and no participants left the study because of adverse events, the company said.

Company estimates and next steps

The company said the result suggests VAX-31 could "deliver broader coverage while maintaining the magnitude of immune responses," according to pharmaphorum. Based on current epidemiology, Vaxcyte estimates that VAX-31 could offer an incremental 13% to 36% increase in coverage of serotypes involved in invasive pneumococcal disease compared with currently available adult vaccines. These are company estimates, not trial outcomes.

"Today's adult PCVs differ in the serotypes they cover, requiring trade-offs between coverage of currently circulating disease-causing serotypes and preserving coverage of historically important serotypes," Luis Jodar, Vaxcyte's chief medical officer, said, as quoted by pharmaphorum. "VAX-31 is designed to bring both into a single 31-valent vaccine."

OPUS-1 is the first of three adult Phase 3 trials. OPUS-2 is studying co-administration with seasonal influenza vaccine and OPUS-3 is studying adults previously vaccinated with other pneumococcal conjugate vaccines; both have completed enrollment, with results expected in the first half of 2027, pharmaphorum reported. Vaxcyte plans a manufacturing consistency study before a regulatory submission targeted for the first half of 2028, according to RTTNews.

Investors reacted strongly. Vaxcyte shares were trading at $86.73 before the market opened on October 5, up 53.56% from Friday's close of $56.48, RTTNews reported. Pharmaphorum put the company's market capitalization at close to $11 billion after the readout.

Vaxcyte is also developing VAX-24, another pneumococcal candidate with Phase 2 data in adults and infants, as well as VAX-A1, a Phase 1 candidate targeting Group A streptococcus, and VAX-GI, an early program targeting Shigella.