VAXNEUVANCE Suspension for injection Ref.[28342] Active ingredients: Pneumococcus, purified polysaccharides antigen

Pharmacotherapeutic group: vaccines, pneumococcal vaccines\
ATC code: J07AL02

Mechanism of action

Vaxneuvance contains 15 purified pneumococcal capsular polysaccharides from Streptococcus pneumoniae (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, 22F, 23F, 33F), each conjugated to a carrier protein (CRM₁₉₇). Vaxneuvance elicits a T-cell dependent immune response to induce antibodies that enhance opsonisation, phagocytosis, and killing of pneumococci to protect against pneumococcal disease.

Clinical immunogenicity in immunocompetent adults ≥18 years of age

Immune responses following natural exposure to Streptococcus pneumoniae or following pneumococcal vaccination can be determined by measuring opsonophagocytic activity (OPA) and immunoglobulin G (IgG) responses. OPA represents functional antibodies capable of opsonizing pneumococcal capsular polysaccharides for presentation to phagocytic cells for engulfment and subsequent killing, and are considered an important immunologic surrogate measure of protection against pneumococcal disease in adults. OPA titres are expressed as the reciprocal of the highest serum dilution that reduces the survival of the pneumococci by at least 50%. A validated multiplex opsonophagocytic assay (MOPA) was used to measure serotype-specific OPA titres for each of the 15 serotypes in Vaxneuvance.

Five clinical studies (Protocol 007, Protocol 016, Protocol 017, Protocol 019, and Protocol 021) conducted in the Americas, Europe and Asia Pacific evaluated the immunogenicity of Vaxneuvance in healthy and immunocompetent adults across different age groups including individuals with or without previous pneumococcal vaccination. Each clinical study included adults with stable underlying medical conditions (e.g., diabetes mellitus, renal disorders, chronic heart disease, chronic liver disease, chronic lung disease including asthma) and/or behavioural risk factors (e.g., current tobacco use, increased alcohol consumption) that are known to increase the risk of pneumococcal disease.

In each study, immunogenicity was assessed by serotype-specific OPA and IgG responses at 30 days postvaccination. Study endpoints included OPA geometric mean titres (GMTs) and IgG geometric mean concentrations (GMCs). The pivotal study (Protocol 019) aimed to show noninferiority of the OPA GMTs for 12 of 13 serotypes that Vaxneuvance shares with the 13-valent pneumococcal polysaccharide conjugate vaccine, noninferiority and superiority for the shared serotype 3, and superiority for serotypes 22F and 33F, unique to Vaxneuvance. Superiority assessment of Vaxneuvance to the 13-valent pneumococcal polysaccharide conjugate vaccine was based on the between-group comparisons of OPA GMTs and the proportions of participants with a ≥4-fold rise in serotype-specific OPA titres from prevaccination to 30 days postvaccination.

Pneumococcal vaccine-naïve adults

In the pivotal, double-blind, active comparator-controlled study (Protocol 019), 1,205 immunocompetent pneumococcal vaccine-naïve subjects ≥50 years of age were randomised to receive Vaxneuvance or the 13-valent pneumococcal polysaccharide conjugate vaccine. The median age of participants was 66 years (range: 50 to 92 years), with approximately 69% over 65 years of age, and approximately 12% over 75 years of age. 57.3% were female and 87% reported history of at least one underlying medical condition.

The study demonstrated that Vaxneuvance is noninferior to the 13-valent pneumococcal polysaccharide conjugate vaccine for the 13 shared serotypes and superior for the 2 unique serotypes and for the shared serotype 3. Table 2 summarises the OPA GMTs at 30 days postvaccination. IgG GMCs were generally consistent with the results observed for the OPA GMTs.

Table 2. Serotype-specific OPA GMTs at 30 days Postvaccination in Pneumococcal Vaccine-Naïve Adults ≥50 Years of age (Protocol 019):.

^* GMTs, GMT ratio, and 95% CI are estimated from a cLDA model.
^† A conclusion of non-inferiority for the 13 shared serotypes is based on the lower bound of the 95% CI for the estimated GMT ratio (Vaxneuvance/13-valent PCV) being > 0.5.
^‡ A conclusion of superiority for serotype 3 is based on the lower bound of the 95% CI for the estimated GMT ratio (Vaxneuvance/13-valent PCV) being >1.2.
^§ A conclusion of superiority for the 2 unique serotypes is based on the lower bound of the 95% CI for the estimated GMT ratio (Vaxneuvance/13-valent PCV) being > 2.0.
N=Number of participants randomised and vaccinated; n=Number of participants contributing to the analysis.
CI=confidence interval; cLDA=constrained longitudinal data analysis; GMT=geometric mean titre (1/dil); OPA=opsonophagocytic activity; PCV=pneumococcal conjugate vaccine.

In a double-blind, descriptive study (Protocol 017), 1,515 immunocompetent subjects 18 to 49 years of age with or without risk factors for pneumococcal disease were randomised 3:1 and received Vaxneuvance or the 13-valent pneumococcal polysaccharide conjugate vaccine, followed by PPV23 6 months later. Risk factors for pneumococcal disease included the following: diabetes mellitus, chronic heart disease including heart failure, chronic liver disease with compensated cirrhosis, chronic lung disease including persistent asthma and chronic obstructive pulmonary disease (COPD), current tobacco use, and increased alcohol consumption. Overall, of those who received Vaxneuvance, 285 (25.2%) had no risk factor, 620 (54.7%) had 1 risk factor, and 228 (20.1%) had 2 or more risk factors.

Vaxneuvance elicited immune responses to all 15 serotypes contained in the vaccine as assessed by OPA GMTs (Table 3) and IgG GMCs. OPA GMTs and IgG GMCs were generally comparable between the two vaccination groups for the 13 shared serotypes and higher in the Vaxneuvance group for the 2 unique serotypes. Following vaccination with PPV23, OPA GMTs and IgG GMCs were generally comparable between the two vaccination groups for all 15 serotypes.

In a subgroup analysis based on the number of reported risk factors, Vaxneuvance elicited immune responses to all 15 serotypes contained in the vaccine as assessed by OPA GMTs and IgG GMCs at 30 days postvaccination in adults with no, 1, or 2 or more risk factors. The results in each subgroup were generally consistent with those observed in the overall study population. Sequential administration of Vaxneuvance followed 6 months later by PPV23 was also immunogenic for all 15 serotypes contained in Vaxneuvance.

Table 3. Serotype-specific OPA GMTs at 30 days Postvaccination in Pneumococcal Vaccine-Naïve Adults 18-49 Years of Age With or Without Risk Factors for Pneumococcal Disease (Protocol 017):

^* The within-group 95% CIs are obtained by exponentiating the CIs of the mean of the natural log values based on the t-distribution.
N=Number of participants randomised and vaccinated; n=Number of participants contributing to the analysis.
CI=confidence interval; GMT=geometric mean titre (1/dil); OPA=opsonophagocytic activity; PCV=pneumococcal conjugate vaccine.

Sequential administration of pneumococcal vaccines in adults

The sequential administration of Vaxneuvance followed by PPV23 was assessed in Protocol 016, Protocol 017 (see section 5.1, Pneumococcal vaccine-naïve adults), and Protocol 018 (see section 5.1, Adults living with HIV).

In a double-blind, active comparator-controlled study (Protocol 016), 652 pneumococcal vaccine-naïve subjects ≥50 years of age were randomised to receive Vaxneuvance or the 13-valent pneumococcal polysaccharide conjugate vaccine, followed by PPV23 one year later.

Following vaccination with PPV23, OPA GMTs and IgG GMCs were comparable between the two vaccination groups for all 15 serotypes in Vaxneuvance.

Immune responses elicited by Vaxneuvance persisted up to 12 months postvaccination as assessed by OPA GMTs and IgG GMCs. Serotype-specific OPA GMTs declined over time, as they were lower at Month 12 than Day 30, but remained above baseline levels for all the serotypes contained in either Vaxneuvance or the 13-valent pneumococcal polysaccharide conjugate vaccine. OPA GMTs and IgG GMCs were generally comparable between the intervention groups at Month 12 for the 13 shared serotypes and higher for the 2 unique serotypes among recipients of Vaxneuvance.

Adults with prior pneumococcal vaccination

In a double-blind, descriptive study (Protocol 007), 253 subjects ≥65 years of age who were previously vaccinated with PPV23 at least one year prior to study entry were randomised to receive Vaxneuvance or the 13-valent pneumococcal polysaccharide conjugate vaccine.

IgG GMCs and OPA GMTs were generally comparable between the two vaccination groups for the 13 shared serotypes and higher in the Vaxneuvance group for the 2 unique serotypes.

In a clinical study, in which another PCV was administered ≤ 1 year after PPV23, reduced immune responses were observed for the common serotypes compared to immune responses observed when PCV was given either alone or before PPV23. The clinical significance of this is unknown.

Clinical immunogenicity in special populations

Adults living with HIV

In a double-blind, descriptive study (Protocol 018), 302 pneumococcal vaccine-naïve subjects ≥18 years of age living with HIV with CD4+ T-cell count ≥50 cells/µL and plasma HIV ribonucleic acid (RNA) <50,000 copies/mL were randomised to receive Vaxneuvance or the 13-valent pneumococcal polysaccharide conjugate vaccine, followed by PPV23 2 months later. The majority of participants had a CD4+ T-cell count ≥200 cells/µL; 4 (1.3%) had a CD4+ T-cell count ≥50 to <200 cells/µL, 152 (50.3%) had a CD4+ T-cell count ≥ 200 to <500 cells/µL, and 146 (48.3%) had a CD4+ T-cell count ≥ 500 cells/µL.

Vaxneuvance elicited immune responses to all 15 serotypes contained in the vaccine as assessed by OPA GMTs and IgG GMCs at 30 days postvaccination. Immune responses seen in the HIV-infected participants were consistently lower compared to healthy participants but comparable for both vaccination groups, except for serotype 4. OPA GMT and IgG GMC for serotype 4 were lower for Vaxneuvance. After sequential administration with PPV23, OPA GMTs and IgG GMCs were generally comparable between the two vaccination groups for all 15 serotypes.