Pfizer presented data from a phase 3 trial of its 20-valent pneumococcal conjugate vaccine (20vPnC) candidate in adults 18 years of age or older not previously vaccinated against pneumococcal disease, and from a Phase 2 proof-of-concept study in infants given a four-dose pediatric series, as part of IDWeek’s virtual 2020 medical congress. Pfizer recently submitted a biologics license application (BLA) for adults 18 years of age or older to the U.S. FDA and is awaiting acceptance of the application for review. The company anticipates submitting a 20vPnC marketing authorization application for adults to the European Medicines Agency in Q1 2021.
The Phase 3 randomized, double-blind trial included 902 adults aged 18 or older with no history of pneumococcal vaccination. The study was designed to compare immune responses after receipt of 20vPnC in adults ≥60 years old to responses in a control group receiving Prevnar 13 or a licensed pneumococcal polysaccharide vaccine (PPSV23). The study also evaluated immune responses of 20vPnC in adults 18 to 59 years (secondary endpoints) and described the safety profile of 20vPnC in all adults ≥18 years old (primary endpoint).
All 20 vaccine serotypes induced robust responses across three age cohorts (≥60 years, 50-59 years, 18-49 years). For the primary immunogenicity objectives in adults ages 60 years or older, the ratio of serotype-specific OPA geometric mean titers (GMTs) responses one month after vaccination were noninferior for all the serotypes in common with licensed Prevnar 13 and six of the seven additional serotypes when compared to a PPSV23. One of the new seven serotypes (serotype 8) missed the noninferiority lower bound criteria but showed immune responses in other immunological parameters. Immune responses to 20vPnC in the younger age cohorts (18-49 years and 50-59 years) were noninferior to 20vPnC responses in adults 60-64 years; these were secondary immunogenicity endpoints. The most frequent adverse event was injection site pain.
The phase 2 study was a multicenter, randomized, active-controlled, double-blind, two-arm parallel design, conducted at investigator sites in the United States. There were 460 infants ages 42 to 98 days randomized (1:1) to receive either 20vPnC or Prevnar 13 at 2, 4, and 6 months of age (infant series, Doses 1 through 3) and 12 months of age (Dose 4). Overall, the safety profile of a four-dose schedule of 20vPnC was consistent with 13vPnC given in the same schedule. A similar percentage of infants receiving either vaccine experienced local reactions, fever, and other systemic events. In addition, a similar percentage of infants receiving either 20vPnC or 13vPnC experienced an adverse event (AE) within one month after Dose 3 (59% and 56%, respectively) and from Dose 4 to one month after Dose 4 (19% and 25%, respectively). 20vPnC elicited pneumococcal immune responses to all 20 serotypes one month after Dose 3. Booster responses were observed for all serotypes after Dose 4 when comparing the serotype-specific IgG GMCs from one month after Dose 4 to responses both 1 month after Dose 3 and before Dose 4 indicating the induction of immunological memory. 20vPnC elicited functional antibody responses to all 20 serotypes at one month after Dose 3 and one month after Dose 4.
Pfizer’s 20vPnC vaccine candidate includes 13 serotypes already included in Prevnar 13® (pneumococcal 13-valent Conjugate Vaccine [Diphtheria CRM197 Protein]), along with seven new serotypes that are global causes of invasive pneumococcal disease (IPD), and are associated with high case-fatality rates, antibiotic resistance and/or meningitis.
On September 20, 2018, Pfizer announced the U.S. Food and Drug Administration (FDA) granted Breakthrough Therapy Designation for 20vPnC for the prevention of invasive disease and pneumonia in adults age 18 years or older. On September 15, 2020, Pfizer’s 20vPnC also received the FDA’s Breakthrough Therapy Designation for the prevention of disease caused by S. pneumoniae serotypes in the vaccine in infants, children, and adolescents.
The FDA previously granted Fast Track designation for 20vPnC in May 2017 for the pediatric indication25 and in September 2017 for use in adults aged 18 years or older.