Pfizer Inc. (NYSE: PFE) today announced data from a Phase 2 study investigating its hexavalent capsular polysaccharide (CPS) conjugate Group B Streptococcus (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(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 (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 (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.
"Group B Streptococcus can cause potentially devastating diseases in infants, including sepsis, pneumonia and meningitis. Annually, there are nearly 400,000 cases of infant disease and approximately 138,000 stillbirths and infant deaths worldwide due to GBS," said Annaliesa Anderson, Ph.D., Senior Vice President and Chief Scientific Officer, Vaccine Research and Development, Pfizer. "The findings published in NEJM provide hope that maternal vaccination with GBS6 may protect infants against GBS, potentially helping to prevent thousands of cases of illness annually, if it is successfully developed and approved. Building on decades of expertise and knowledge in vaccines, we are committed to helping protect newborns and young infants through maternal immunization."
The Phase 2 placebo-controlled study was divided into three stages.
- Stage 1: Evaluated safety and immunogenicity in 66 healthy, nonpregnant individuals in South Africa.
- Stage 2: The focus of the NEJM publication, is evaluating safety and immunogenicity in 360 healthy pregnant individuals aged 18 to 40 years and their infants in South Africa. Participants were randomly assigned to receive a single dose of GBS6 formulated at 5, 10 or 20 µg/serotype, with or without an AlPO4 adjuvantor placebo, given from late second trimester. The highest antibody responses were generally observed with the GBS6 20 µg dose, formulated without an aluminum phosphate (AlPO4) adjuvant.
- Stage 3: A final formulation is being evaluated in 216 healthy pregnant individuals and their infants in South Africa, the U.S. and U.K.
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 (IgG) 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 µg/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 >0.184 ug/mL varied by serotype and formulation, with 57% to 97% seroresponder rates achieved for the most immunogenic formulation.
About GBS6
Hexavalent anti capsular polysaccharide (CPS) / genetically detoxified diphtheria toxin cross reactive material (CRM) 197 glycoconjugate (GBS6) is being developed as an investigational maternal vaccine to help prevent invasive Group B Streptococcus (GBS) in newborns. Polysaccharides conjugated to CRM have been successfully used by Pfizer in its pneumococcal vaccines, which have a proven track record of safety and effectiveness in millions of infants globally.
GBS6 is designed to offer protection against the six most prominent GBS serotypes, which account for 98% of GBS disease worldwide.1 GBS6 safety and immunogenicity is being evaluated in an ongoing Phase 2, placebo-controlled study in pregnant women and their infants in South Africa, the U.S. and U.K. following a single intramuscular injection during the second or early third trimester of pregnancy. Pfizer is pursuing a clinical development strategy in high-, middle- and low-income countries with the intent to make a successfully developed vaccine available globally as quickly as possible.
In 2016, Pfizer received a grant from the Bill & Melinda Gates Foundation, which supported the ongoing Phase 2 clinical trial of GBS6 as well as the parallel natural history study conducted in South Africa.2
