Positive Topline Data From 31-Valent Pneumococcal Conjugate Vaccine Clinical Study Announced
The vaccine, VAX-31, targets 20 serotypes in common with PCV20, as well as 11 additional serotypes.
Vaxcyte has announced positive topline data from a phase 1/2 clinical study of VAX-31, a 31-valent pneumococcal conjugate vaccine (PCV) for the prevention of invasive pneumococcal disease.1 The study evaluated the safety, tolerability, and immunogenicity of VAX-31.
In a randomized, observer-blind, active-controlled, dose-finding clinical study (NCT06151288) a total of 1015 healthy adults aged 50 years and older (phase 1 n=64, phase 2 n=951) received a single injection of VAX-31 at 1 of 3 dose levels—1.1 mcg (low dose), 2.2 mcg (medium dose), and 3.3 mcg (high dose)—for all serotypes excluding serotypes 1, 5, and 22F which were dosed at 1.6 mcg, 3.3 mcg, and 4.4 mcg for low, medium, and high, respectively. All participants were compared to a comparator group of healthy adults who received a dose of Pfizer’s Prevnar 20 (pneumococcal 20-valent conjugate vaccine; PCV20).
Streptococcus pneumonaie poses a serious threat to public health. | Image credit: Dr_Microbe - stock.adobe.com
For all 3 doses, VAX-31 demonstrated “robust [opsonophagocytic activity] immune responses” for all 31 pneumococcal serotypes studied. At the high and medium doses, VAX-31 “met or exceeded the regulatory immunogenicity criteria” for all 31 serotypes; at the low dose, the vaccine met or exceeded regulatory immunogenicity criteria for 29 of the 31 serotypes.
VAX-31 has 20 serotypes common with PCV20: serotypes 1, 3, 4, 5, 6A, 6B, 7F, 8, 9V, 10A, 11A, 12F, 14, 15B, 18C, 19A, 19F, 22F, 23F, and 33F. At the high dose of VAX-31, all 20 serotypes met opsonophagocytic activity response noninferiority criteria. Eighteen of these 20 serotypes had a geometric mean ratio higher than 1.0, and 7 serotypes demonstrated statistically higher immune response. At the middle dose of VAX-31, all 20 serotypes met opsonophagocytic activity response noninferiority criteria, while 13 of 20 had a geometric mean ratio higher than 1.0 and 5 serotypes demonstrated a statistically higher immune response. And at the low dose, 18 of 20 serotypes met opsonophagocytic activity response noninferiorty criteria, with 8 or 20 serotypes having a geometric mean ratio greater than 1.0 and 3 serotypes demonstrating a statistically higher immune response.
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Across the 11 additional serotypes not covered by PCV20—serotypes 2, 7C, 9N, 15A, 16F, 17F, 20B, 23A, 23B, 31, and 35B, all 3 doses of VAX-31 met superiority criteria.
In terms of safety, over 6 months of follow-up, investigators observed that VAX-31 was well tolerated and had a similar safety profile to PCV20 across low, medium, and high doses. No serious adverse events related to the study vaccines were reported, and local and systemic reactions were typically mild to moderate and were not meaningfully different across study cohorts.
“We believe the positive safety, tolerability, and immunogenicity results from the VAX-31 phase 1/2 study affirm the potential of our site-specific, carrier-sparing platform to deliver the broadest spectrum PCVs that provide protection against both currently circulating and historically prevalent strains,” said Vaxcyte CEO and co-found Grant Pickering, in a news release. “Based on the strength and clarity of these data, we have selected VAX-31 for the adult indication and plan to initiate the pivotal, noninferiorty phase 3 study by mid-2025, and announce topline data in 2026.” Pickering added that remaining VAX-31 phase 3 studies would be initiated in 2025 and 2026, with a biologics license application submission “subject to the results of these studies.”
“The public health community continues to highlight the need for broader-protection vaccines to prevent [invasive pneumococcal disease], which is associated with high case-fatality rates, antibiotic resistance, and meningitis,” said Jim Wassil, Vaxcyte’s executive vice president and chief operating officer. “To address this need, VAX-31 was designed to increase coverage to more than 95% of [invasive pneumococcal disease] circulating in adults 50 and older in the United States, with the potential to provide significantly greater coverage relative to today’s standard-of-care adult PCVs.”
Pneumococcal disease is caused by Streptococcus pneumoniae bacteria, and can lead to both invasive pneumococcal disease, such as meningitis and bacteremia, and non-invasive pneumococcal disease, such as pneumonia, otitis media, and sinusitis. Estimates suggest that pneumococcal pneumonia leads to approximately 150,000 hospitalizations each year.
S pneumoniae poses a serious threat to public health: the World Health Organization lists it as a top antibiotic-resistant pathogen, and the CDC lists drug resistant S pneumoniae as a “serious threat.” Although antibiotics are used to treat pneumococcal disease, some strains have developed antibiotic resistance.
Infants are also susceptible to pneumococcal diseases: Currently, S pneumoniae is the leading cause of vaccine-preventable deaths in children aged 5 years or younger. Vaxcyte is evaluating VAX-31 and VAX-24 in infant populations as well. In 2025, the company intends to initiate a phase 2 clinical study during the first quarter of 2025, with topline safety, tolerability, and immunogenicity data for an infant primary 3-dose immunization series in mid-2026. Topline data from a phase 2 study of VAX-24, which is currently fully enrolled with a population of 802 healthy infants, is anticipated during the first quarter of 2025.
READ MORE: Immunization Resource Center
