Vaxcyte’s VAX-31 Meets All Primary Endpoints in Pivotal Phase III OPUS-1 Trial

Key Points

• VAX-31 met all primary endpoints in the Phase III OPUS-1 trial, demonstrating non-inferior immune responses against shared serotypes and superior responses against several unique serotypes compared with licensed vaccines.
• The vaccine was generally well tolerated, with mostly mild-to-moderate reactions and no apparent safety signal or vaccination-related serious adverse events.
• Vaxcyte plans to use OPUS-1 data in a U.S. biologics license application, along with results from additional studies expected in 2027, targeting submission in the first half of 2028.

Vaxcyte NASDAQ: PCVX said its investigational 31-valent pneumococcal conjugate vaccine, VAX-31, met all pre-specified primary immunogenicity endpoints in the pivotal Phase III OPUS-1 trial in adults.

The randomized, double-blind, active-controlled study enrolled 4,047 U.S. adults, including 3,572 participants aged 50 and older and 475 participants aged 18 to 49. VAX-31 is being developed to prevent invasive pneumococcal disease and pneumococcal pneumonia.

Chief Executive Officer and Co-Founder Grant Pickering said the results validate the company’s effort to broaden pneumococcal disease coverage while maintaining immune responses. VAX-31 contains all serotypes included in Prevnar 20, also known as PCV20, and adds serotypes covered by Capvaxive, or PCV21, as well as additional serotypes.

Primary Endpoint Results

In adults aged 50 and older, VAX-31 met all 32 pre-specified co-primary immunogenicity assessments, comprising 28 non-inferiority comparisons for serotypes shared with licensed comparators and four superiority assessments for three VAX-31-unique serotypes and cross-reactive serotype 20B.

The company used opsonophagocytic activity, or OPA, geometric mean titers to assess functional immune responses. For non-inferiority, the lower bound of the 95% confidence interval for the geometric mean ratio had to exceed 0.667, a more stringent threshold than the historical 0.5 benchmark used in pivotal trials for PCV20 and PCV21.

• VAX-31 met the pre-specified non-inferiority criterion for all 28 serotypes shared with PCV20 or PCV21.
• Against PCV20, VAX-31 met the 0.667 non-inferiority threshold for all 20 shared serotypes.
• Against PCV21, VAX-31 met the threshold for 17 of 19 shared serotypes.
• For serotypes 3 and 12F, the lower confidence bounds versus PCV21 did not exceed 0.667, but both exceeded the historical 0.5 threshold and met the higher threshold in comparisons with PCV20.
• VAX-31 met the superiority criterion for serotypes 2, 7C and 20C, which are unique to VAX-31, as well as cross-reactive serotype 20B.

The study also met its immunobridging objective. VAX-31 immune responses in participants aged 18 to 49 were non-inferior to those in VAX-31 recipients aged 50 to 64 across all 32 evaluated responses. Chief Medical Officer Luis Jodar said the finding supports the company’s planned request for an indication beginning at age 18, subject to regulatory review.

Safety Profile

Chief Scientific Officer and Chief Operating Officer Jim Wassil said VAX-31 was generally well tolerated. Solicited local and systemic reactions were predominantly mild to moderate, transient and generally resolved within 48 hours.

Reactogenicity was broadly consistent with PCV20 and PCV21, though injection-site pain and muscle pain occurred somewhat more frequently with VAX-31 in adults aged 50 and older, according to the company.

Unsolicited adverse events were monitored through one month after vaccination, while medically attended adverse events, newly diagnosed chronic illnesses and serious adverse events were followed for six months. Vaxcyte said there was no apparent pattern suggesting a safety signal, no serious adverse events considered related to vaccination, and no study discontinuations due to adverse events.

Four deaths occurred among older participants: two in the VAX-31 group and two in the PCV21 group. All were assessed as unrelated to vaccination.

Regulatory and Commercial Plans

Vaxcyte said OPUS-1 will serve as the cornerstone of its planned U.S. Biologics License Application, or BLA. The application is also expected to include results from OPUS-2 and OPUS-3, which are expected in the first half of 2027, as well as a manufacturing consistency study.

President and Chief Financial Officer Andrew Guggenhime said the additional studies are needed in part to establish the required safety database. The company expects to submit its BLA in the first half of 2028 after completing the remaining clinical and manufacturing work.

Vaxcyte said it has completed a dedicated manufacturing facility intended to produce more than tens of millions of doses annually, while a finished-product line is being built in Greenville, North Carolina. The company said it is already manufacturing through contract manufacturers and beginning inventory-building activities for a potential launch.

Chief Commercial Officer Mike Mullette said Vaxcyte intends initially to commercialize VAX-31 independently in the U.S., focusing on retail pharmacies and large health systems. For markets outside the U.S., the company said it may consider strategic partnerships.

Pickering said Vaxcyte believes VAX-31 covers serotypes responsible for 95% of invasive pneumococcal disease and 88% of pneumococcal pneumonia among U.S. adults aged 50 and older. He said the company expects regulators to review the complete data package, including the individual comparisons with both licensed vaccines.

About Vaxcyte (NASDAQ:PCVX)

Vaxcyte, Inc NASDAQ: PCVX is a clinical-stage biotechnology company focused on developing vaccines to help prevent serious bacterial infections. The company uses its cell-free protein synthesis and advanced conjugation technologies to design vaccines intended to provide broad and durable protection while addressing limitations of existing vaccine products.

Vaxcyte's lead programs are pneumococcal conjugate vaccine candidates, including VAX-24 and VAX-31, which are designed to target a broad range of pneumococcal serotypes.

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