Vaxcyte Launches VAX-31 Phase 3 Program, Targets Adult BLA Filing by End of 2027

Vaxcyte has dosed the first participants in its OPUS-3 Phase 3 trial of VAX-31, a 31-valent pneumococcal conjugate vaccine, as part of a broader adult program aligned with the U.S. FDA to support a future Biologics License Application. The company plans to submit a BLA by the end of next year.

Executives used a presentation at an annual biotech summit to highlight progress across the company's pneumococcal conjugate vaccine (PCV) pipeline, with a particular focus on VAX-31 and the Phase 3 adult program now underway. VAX-31 holds Breakthrough Therapy designation and is described as the broadest-spectrum pneumococcal conjugate vaccine in the clinic.

The Chief Executive Officer said Vaxcyte has become known for its PCV franchise, which he described as the company's "headliner." The CEO emphasized that pneumococcal disease remains a significant cause of illness despite the impact of existing vaccines, and argued that today's technologies have been constrained by limitations in how the vaccines are constructed.

The CEO said Vaxcyte has developed a way to assemble conjugates "more nimbly" to expand serotype coverage without sacrificing immunogenicity. He pointed to the historical pattern in PCVs: as vaccines remove covered serotypes from circulation, other serotypes tend to fill the void, driving the industry's progression from 7- to 13- to 15- to 20- and 21-valent vaccines.

According to the CEO, current manufacturers have said they cannot effectively go beyond 20 or 21 serotypes. He said Vaxcyte's approach allows it to surpass that ceiling, and that the company's VAX-31 adult data has already shown what he called the best results generated in the class, with an infant readout still pending.

The CEO said Vaxcyte has launched a Phase 3 program for VAX-31 following Phase 2 results that, in his view, differed from historical experience in the class by increasing coverage while also improving immune responses. He said the Phase 3 package was designed in close consultation with the FDA.

He described the pivotal trial, OPUS-1, as a 4,000-subject study in adults aged 50 and older. The study will compare VAX-31 against both current standards of care—Prevnar 20 and Merck's CAPVAXIVE—aiming to demonstrate non-inferiority for overlapping serotypes and superiority for serotypes not included in comparator vaccines.

The CEO said the FDA and industry have been moving toward a higher non-inferiority standard in adults. He noted Vaxcyte agreed to a stricter margin than has been used historically, and said the company believes its Phase 2 data supports that approach.

Beyond the pivotal study, executives outlined additional Phase 3 efforts, including a concomitant administration study pairing VAX-31 with influenza vaccines, reflecting common pharmacy vaccination practices; a prior-vaccination (boosting) study launched "yesterday," designed to evaluate responses in adults who previously received a lower-valent pneumococcal vaccine, with the goal of supporting a "catch-up" recommendation; and a manufacturing consistency study planned as part of the filing package.

The CEO said the predictability of the PCV class has historically been high, stating that PCVs with successful Phase 2 data have gone on to succeed in Phase 3 and receive approval.

The CEO described the PCV segment as an $8 billion market that could expand as adult vaccination increases. The President and CFO added that adult pneumococcal vaccination has historically been dominated by the U.S., but said that is changing as more countries recommend broader adult vaccination.

The President and CFO said recent reported results from CAPVAXIVE and Pfizer show "significant growth ex-U.S." and argued that Vaxcyte could benefit from market development already underway. He also noted the company recently hired its first chief commercial officer, Mike Mullette, to help assess international strategy.

The President and CFO said Vaxcyte is still determining which markets it may commercialize on its own versus where it might partner, particularly given the scope of a global infant opportunity.

The CEO contrasted the coverage profiles of Prevnar 20 and CAPVAXIVE, describing CAPVAXIVE's strategy as shifting toward more recently circulating serotypes at the expense of older serotypes included in earlier vaccines. He said that difference in coverage contributed to recommendations that allow use of either vaccine rather than selecting one outright.

He also cited CAPVAXIVE's early commercial traction, saying it has sold over $750 million in its first full year and that its market share appears to be approaching 40% to 45%. He suggested CAPVAXIVE could become the market leader by the time VAX-31 launches.

The CEO said VAX-31 is designed to cover both older and newer serotypes, offering what he described as a more comprehensive single option. He also detailed the analytical plan for OPUS-1, explaining that for serotypes shared among all three vaccines, Vaxcyte plans to meet non-inferiority versus at least one comparator, with additional head-to-head analyses for serotypes shared with only one of the marketed vaccines.

Following a recent financing, Vaxcyte has over $3 billion pro forma, funding multiple planned Phase 3 studies and supporting international commercialization strategy decisions. The company recently raised $550 million in equity.