Pfizer announces NEJM publication of GBS maternal vaccine candidate data

Pfizer announced data from a Phase 2 study investigating its hexavalent capsular polysaccharide, or CPS, conjugate Group B Streptococcus, or GBS, vaccine candidate, GBS6, being developed for maternal administration to protect infants against invasive GBS disease. In stage two of the three-part study, which enrolled 360 healthy pregnant individuals, GBS6 generated robust maternal antibody responses against the six GBS CPS serotypes included in the vaccine, and these antibodies were efficiently transferred to infants at ratios of ~0.4-1.3 depending on GBS6 group. Based on a parallel natural history study conducted in South Africa, the Phase 2 study immunogenicity data suggest that GBS6 may offer meaningful protection against invasive GBS disease in newborns and young infants. The results were published in The New England Journal of Medicine, or NEJM, and will inform a planned Phase 3 clinical development program. In both the mothers and infants, the safety profile was similar between the vaccine and placebo groups. Local reactions were generally mild or moderate and of short duration with pain at the injection site being the most frequently reported event. Solicited systemic events were similar among the GBS6 groups and the placebo group, with most events being mild or moderate. Overall, 2 to 8% of participants in the GBS6 groups, depending on dose, and 5% of those in the placebo group reported fever. Among pregnant individuals, adverse events, or AEs, occurred in 45% to 70% of the participants in the GBS6 groups, depending on dose, and in 61% of those in the placebo group. The most common AEs and serious adverse events, or SAEs, were conditions that are related to pregnancy. Among the infants, AEs occurred in 62% to 75% of the participants in the GBS6 groups, depending on dose, and in 74% of those in the placebo group. None of the SAEs were deemed related to the vaccine candidate. A parallel natural history study conducted in South Africa is also reported in the same issue of NEJM. This study enrolled approximately 18,000 mother-infant pairs to estimate anti-CPS immunoglobulin antibody concentrations in infant sera associated with risk of invasive disease through 89 days of age after delivery. Antibody concentrations associated with protective natural immunity obtained from this second study were compared to maternally transferred GBS6 vaccine-induced antibody levels in infants in the Phase 2 study to determine the percentage of infants that have antibody levels exceeding those associated with protection. Naturally acquired anti-CPS IgG concentrations correlated with reduced risk of disease in the natural history study with similar results for serotypes Ia, III, and an aggregate of all GBS6 serotypes that indicated 75-95% protective titers of 0.184-0.827 microgram/mL anti-CPS IgG. The proportion of infants born to immunized mothers in stage two of the Phase 2 study with anti-CPS IgG antibody concentrations greater than0.184 ug/mL varied by serotype and formulation, with 57% to 97% seroresponder rates achieved for the most immunogenic formulation.