Vaccine Information: VAXNEUVANCE (Page 2 of 4)

8 USE IN SPECIFIC POPULATIONS

8.1 Pregnancy

Risk Summary

All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.

There are no adequate and well-controlled studies of VAXNEUVANCE in pregnant women. Available data on VAXNEUVANCE administered to pregnant women are insufficient to inform vaccine-associated risks in pregnancy.

Developmental toxicity studies have been performed in female rats administered a human dose of VAXNEUVANCE on four occasions; twice prior to mating, once during gestation and once during lactation. These studies revealed no evidence of harm to the fetus due to VAXNEUVANCE [see Animal Data below].

Data

Animal Data

Developmental toxicity studies have been performed in female rats. In these studies, female rats received a human dose of VAXNEUVANCE by intramuscular injection on day 28 and day 7 prior to mating, and on gestation day 6 and on lactation day 7. No vaccine related fetal malformations or variations were observed. No adverse effect on pup weight up to post-natal day 21 was noted.

8.2 Lactation

Risk Summary

Human data are not available to assess the impact of VAXNEUVANCE on milk production, its presence in breast milk, or its effects on the breastfed child. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for VAXNEUVANCE and any potential adverse effects on the breastfed child from VAXNEUVANCE or from the underlying maternal condition. For preventive vaccines, the underlying condition is susceptibility to disease prevented by the vaccine.

8.4 Pediatric Use

The safety and effectiveness of VAXNEUVANCE have been established in individuals 6 weeks through 17 years of age [see Adverse Reactions (6.1) and Clinical Studies (14.1)]. The safety and effectiveness of VAXNEUVANCE in individuals younger than 6 weeks of age have not been established.

8.5 Geriatric Use

Of the 4,389 individuals aged 50 years and older who received VAXNEUVANCE, 2,478 (56.5%) were 65 years and older, and 479 (10.9%) were 75 years and older [see Adverse Reactions (6.1) and Clinical Studies (14.1)]. Overall, there were no clinically meaningful differences in the safety profile or immune responses observed in older individuals (65 to 74 years and 75 years of age and older) when compared to younger individuals.

8.6 Individuals at Increased Risk for Pneumococcal Disease

Infants Born Prematurely

The safety and immunogenicity of VAXNEUVANCE were evaluated in preterm infants (<37 weeks gestation at birth) who were randomized to receive a complete 4-dose series of either VAXNEUVANCE (N=142) or Prevnar 13 (N=144) within Study 8, Study 9, and Study 10. Participants in these studies may have received either US-licensed or non-US licensed concomitant vaccines according to the local recommended schedule. In descriptive analyses, serotype-specific immunoglobulin G (IgG) and opsonophagocytic activity (OPA) responses at 30 days postdose 3, predose 4 and at 30 days postdose 4 were numerically similar between vaccination groups for the 13 shared serotypes and higher in VAXNEUVANCE for the 2 unique serotypes. The safety profile of VAXNEUVANCE was similar to the safety profile of Prevnar 13. In addition, the immune responses and safety profile in preterm infants receiving a 4-dose series of VAXNEUVANCE were similar to those observed in term infants in these studies. The effectiveness of VAXNEUVANCE in infants born prematurely has not been established.

Children with Sickle Cell Disease

In a double-blind, descriptive study (Study 13, NCT03731182), the safety and immunogenicity of VAXNEUVANCE were evaluated in children 5 through 17 years of age with sickle cell disease. Participants were randomized 2:1 to receive a single dose of VAXNEUVANCE (N=70) or Prevnar 13 (N=34). Immune responses were assessed by serotype-specific IgG GMCs and OPA GMTs at 30 days postvaccination for all 15 serotypes contained in VAXNEUVANCE. For all vaccine serotypes included in VAXNEUVANCE, serotype-specific IgG GMCs and OPA GMTs were higher following vaccination compared to pre-vaccination. IgG GMCs and OPA GMTs were numerically similar between the two vaccination groups for the 13 shared serotypes and higher in VAXNEUVANCE for serotypes 22F and 33F. The safety profile of VAXNEUVANCE was similar to the safety profile of Prevnar 13. The effectiveness of VAXNEUVANCE in children with sickle cell disease has not been established.

Individuals with HIV Infection

Children with HIV Infection

In a double-blind, descriptive study (Study 14, NCT03921424), the safety and immunogenicity of VAXNEUVANCE were evaluated in HIV-infected children 6 through 17 years of age, with CD4+ T-cell count ≥200 cells per microliter and plasma HIV RNA value <50,000 copies/mL. Participants were randomized to receive a single dose of VAXNEUVANCE (N=203) or Prevnar 13 (N=204), followed by PNEUMOVAX 23 two months later. For all vaccine serotypes included in VAXNEUVANCE, serotype-specific IgG GMCs and OPA GMTs were higher following vaccination compared to pre-vaccination. Serotype-specific IgG GMCs and OPA GMTs were numerically similar for the 13 shared serotypes and higher for the 2 unique serotypes (22F and 33F) at 30 days following vaccination with VAXNEUVANCE or Prevnar 13 and were numerically similar for all 15 serotypes contained in VAXNEUVANCE at 30 days following subsequent vaccination with PNEUMOVAX 23. The safety profile of VAXNEUVANCE was similar to the safety profile of Prevnar 13. The effectiveness of VAXNEUVANCE in HIV-infected children has not been established.

Adults with HIV Infection

In a double-blind, descriptive study (Study 7), the safety and immunogenicity of VAXNEUVANCE were evaluated in pneumococcal vaccine-naïve HIV-infected adults 18 years of age and older, with CD4+ T-cell count ≥50 cells per microliter and plasma HIV RNA value <50,000 copies/mL. Participants were randomized to receive VAXNEUVANCE (N=152) or Prevnar 13 (N=150), followed by PNEUMOVAX 23 two months later [see Adverse Reactions (6.1)]. Anti-pneumococcal opsonophagocytic activity (OPA) geometric mean antibody titers (GMTs) were higher after administration of VAXNEUVANCE, compared to pre-vaccination, for the 15 serotypes contained in VAXNEUVANCE. After sequential administration with PNEUMOVAX 23, OPA GMTs observed at 30 days after PNEUMOVAX 23 vaccination were numerically similar between the two vaccination groups for all 15 serotypes contained in VAXNEUVANCE. The safety profile of VAXNEUVANCE was similar to the safety profile of Prevnar 13. The effectiveness of VAXNEUVANCE in HIV-infected adults has not been established.

11 DESCRIPTION

VAXNEUVANCE (Pneumococcal 15-valent Conjugate Vaccine) is a sterile suspension of purified capsular polysaccharides from S. pneumoniae serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, 22F, 23F, and 33F individually conjugated to CRM197 . Each pneumococcal capsular polysaccharide is activated via sodium metaperiodate oxidation and then individually conjugated to CRM197 carrier protein via reductive amination. CRM197 is a non-toxic variant of diphtheria toxin (originating from Corynebacterium diphtheriae C7) expressed recombinantly in Pseudomonas fluorescens.

Each of the fifteen serotypes is manufactured independently using the same manufacturing steps with slight variations to accommodate for differences in strains, polysaccharides and process stream properties. Each S. pneumoniae serotype is grown in media containing yeast extract, dextrose, salts and soy peptone. Each polysaccharide is purified by a series of chemical and physical methods. Then each polysaccharide is chemically activated and conjugated to the carrier protein CRM197 to form each glycoconjugate. CRM197 is isolated from cultures grown in a glycerol-based, chemically-defined, salt medium and purified by chromatography and ultrafiltration. The final vaccine is prepared by blending the fifteen glycoconjugates with aluminum phosphate adjuvant in a final buffer containing histidine, polysorbate 20 and sodium chloride.

Each 0.5 mL dose contains 2.0 mcg each of S. pneumoniae polysaccharide serotypes 1, 3, 4, 5, 6A, 7F, 9V, 14, 18C, 19A, 19F, 22F, 23F, and 33F, and 4.0 mcg of polysaccharide serotype 6B, 30 mcg of CRM197 carrier protein, 1.55 mg L-histidine, 1 mg of polysorbate 20, 4.50 mg sodium chloride, and 125 mcg of aluminum as aluminum phosphate adjuvant. VAXNEUVANCE does not contain any preservatives.

The tip cap and plunger stopper of the prefilled syringe are not made with natural rubber latex.

12 CLINICAL PHARMACOLOGY

12.1 Mechanism of Action

Protection against invasive disease is conferred mainly by antibodies (Immunoglobulin G [IgG] directed against capsular polysaccharides) and opsonophagocytic activity (OPA) against S. pneumoniae. VAXNEUVANCE induces IgG antibodies and OPA against the serotypes contained in the vaccine.

13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

VAXNEUVANCE has not been evaluated for carcinogenic or mutagenic potential or for impairment of male fertility in animals. VAXNEUVANCE administered to female rats had no effect on fertility [see Use in Specific Populations (8.1)] .

14 CLINICAL STUDIES

Immune responses elicited by VAXNEUVANCE and Prevnar 13 in children were measured by a pneumococcal electrochemiluminescence (Pn ECL) assay for total IgG and a multiplexed opsonophagocytic assay (MOPA) for opsonophagocytic killing for the 15 pneumococcal serotypes contained in VAXNEUVANCE postdose 3, predose 4 and postdose 4. In children, a serotype-specific Immunoglobulin G (IgG) antibody level corresponding to ≥0.35 mcg/mL using the WHO enzyme linked immunosorbent assay (ELISA) has been used as the threshold value for the clinical evaluation of pneumococcal conjugate vaccines. Immune responses elicited by VAXNEUVANCE and Prevnar 13 in adults were measured by MOPA and Pn ECL assays for the 15 pneumococcal serotypes contained in VAXNEUVANCE pre- and post-vaccination.

14.1 Clinical Trials in Children

Children Receiving a 4-Dose Series

In a double-blind, active comparator-controlled study (Study 8), participants were randomized to receive VAXNEUVANCE (N=860) or Prevnar 13 (N=860) in a 4-dose series; the first 3 doses were administered to infants at 2, 4, and 6 months of age and the fourth dose was administered to children 12 through 15 months of age. Pentacel (US participants) or a non-US-licensed DTaP-IPV-Hib vaccine (non-US participants), RECOMBIVAX HB, and RotaTeq were administered concomitantly with each of the 3 infant doses. VAQTA, M-M-R II, VARIVAX, and Hiberix were administered concomitantly with the fourth dose. [See Adverse Reactions (6.1) and Clinical Studies (14.3).]

Study 8 assessed serotype-specific IgG response rates, IgG geometric mean concentrations (GMCs), and opsonophagocytic activity (OPA) geometric mean titers (GMTs), for all 15 serotypes contained in VAXNEUVANCE. At 30 days postdose 3, VAXNEUVANCE was noninferior to Prevnar 13 for the 13 shared serotypes, as assessed by the proportion of participants meeting the serotype-specific IgG threshold value of ≥0.35 mcg/mL (response rate). VAXNEUVANCE was noninferior for the 2 unique vaccine serotypes, as assessed by the IgG response rates for serotypes 22F and 33F compared with the response rate for serotype 6B (the lowest response rate for any of the shared serotypes in Prevnar 13 among US participants, excluding serotype 3) at 30 days postdose 3 (Table 9).

Table 9: Proportions of US Participants with IgG Response Rates ≥0.35 mcg/mL at 30 Days Following Dose 3 in Infants Administered VAXNEUVANCE at 2, 4 and 6 Months of Age (Study 8)
PneumococcalSerotype VAXNEUVANCE(n=452-455) Prevnar 13(n=426-430) Percentage Point Difference(VAXNEUVANCE – Prevnar 13) (95% CI)*
Observed ResponsePercentage Observed ResponsePercentage
n=Number of participants contributing to the analysis.CI=Confidence interval; IgG=Immunoglobulin G.
*
CIs are based on the Miettinen & Nurminen method.
A conclusion of non-inferiority of VAXNEUVANCE to Prevnar 13 is based on the lower bound of the 2-sided 95% CI for the difference in percentages (VAXNEUVANCE — Prevnar 13) being >-10 percentage points.
A conclusion of non-inferiority of VAXNEUVANCE to Prevnar 13 is based on the comparison of the response rate for the 2 additional serotypes to the lowest responding Prevnar 13 serotype (serotype 6B), excluding serotype 3.
Serotype
1 93.8 98.6 -4.8 (-7.5, -2.4)
3 93.1 74.0 19.1 (14.4, 24.0)
4 94.7 98.1 -3.4 (-6.1, -1.0)
5 93.4 96.0 -2.6 (-5.7, 0.3)
6A 92.7 99.3 -6.6 (-9.4, -4.2)
6B 86.7 89.9 -3.2 (-7.5, 1.1)
7F 98.7 100.0 -1.3 (-2.9, -0.4)
9V 96.7 97.2 -0.5 (-2.9, 1.9)
14 97.8 98.1 -0.3 (-2.4, 1.7)
18C 96.2 98.1 -1.9 (-4.3, 0.3)
19A 97.4 99.8 -2.4 (-4.3, -1.0)
19F 98.5 100.0 -1.5 (-3.2, -0.6)
23F 89.8 91.4 -1.5 (-5.4, 2.4)
Additional Serotypes
22F 98.0 8.1 (5.1, 11.5)
33F 84.8 -5.1 (-9.5, -0.7)

At 30 days postdose 3, serotype-specific IgG GMCs in the VAXNEUVANCE group were noninferior to Prevnar 13 for 12 of the 13 shared serotypes, except for serotype 6A. The IgG response to serotype 6A missed the prespecified noninferiority criterion by a small margin (the lower bound of the 2-sided 95% CI for the GMC ratio [VAXNEUVANCE/Prevnar 13] being 0.48 versus >0.5). VAXNEUVANCE was noninferior to Prevnar 13 for the 2 unique serotypes, as assessed by serotype-specific IgG GMCs for serotypes 22F and 33F compared with the IgG GMCs for serotype 4 (the lowest IgG GMC for any of the shared serotypes in Prevnar 13 among US participants, excluding serotype 3) (Table 10).

Table 10: Serotype-Specific IgG GMCs at 30 Days Following Dose 3 in US Infants Administered VAXNEUVANCE at 2, 4 and 6 Months of Age (Study 8)
PneumococcalSerotype VAXNEUVANCE(n=452-455) Prevnar 13(n=426-430) GMC Ratio *(VAXNEUVANCE/Prevnar 13) (95% CI)*
GMC GMC
n=Number of participants contributing to the analysis.CI=Confidence interval; GMC=Geometric mean concentration (mcg/mL); IgG=Immunoglobulin G.
*
GMC ratio and CI are calculated using the t-distribution with the variance estimate from a serotype-specific linear model utilizing the natural log-transformed antibody concentrations as the response and a single term for vaccination group.
A conclusion of non-inferiority of VAXNEUVANCE to Prevnar 13 is based on the lower bound of the 2-sided 95% CI for the GMC ratio (VAXNEUVANCE/Prevnar 13) being >0.5.
A conclusion of non-inferiority of VAXNEUVANCE to Prevnar 13 is based on the comparison of the GMC for the 2 additional serotypes to the lowest responding Prevnar 13 serotype (serotype 4), excluding serotype 3.
Serotype
1 1.02 1.54 0.66 (0.61, 0.73)
3 0.96 0.56 1.70 (1.54, 1.86)
4 1.07 1.11 0.97 (0.89, 1.06)
5 1.29 1.69 0.76 (0.68, 0.85)
6A 1.33 2.48 0.53 (0.48, 0.60)
6B 1.42 1.58 0.90 (0.76, 1.06)
7F 2.17 2.83 0.77 (0.70, 0.84)
9V 1.47 1.48 1.00 (0.90, 1.10)
14 4.17 5.57 0.75 (0.66, 0.85)
18C 1.29 1.55 0.83 (0.76, 0.91)
19A 1.39 1.88 0.74 (0.67, 0.82)
19F 1.82 2.33 0.78 (0.72, 0.85)
23F 1.09 1.23 0.89 (0.79, 1.01)
Additional Serotypes
22F 4.01 3.63 (3.26, 4.04)
33F 1.38 1.25 (1.09, 1.44)

At 30 days postdose 4, serotype-specific IgG GMCs for VAXNEUVANCE were noninferior to Prevnar 13 for all 13 shared serotypes (the lower bound of the 2-sided 95% CI for the GMC ratio [VAXNEUVANCE/Prevnar 13] being >0.5) and for the 2 unique serotypes 22F and 33F as assessed by the IgG GMCs for serotypes 22F and 33F compared with the IgG GMCs for serotype 4 (the lowest IgG GMC for any of the shared serotypes in Prevnar 13 among US participants, excluding serotype 3) (Table 11).

Table 11: Serotype-Specific IgG GMCs at 30 Days Following Dose 4 in US Infants Administered VAXNEUVANCE at 2, 4, 6 and 12 to 15 Months of Age (Study 8)
PneumococcalSerotype VAXNEUVANCE(n=466-470) Prevnar 13(n=443-447) GMC Ratio *(VAXNEUVANCE/Prevnar 13) (95% CI)*
GMC GMC
n=Number of participants contributing to the analysis.CI=Confidence interval; GMC=Geometric mean concentration (mcg/mL); IgG=Immunoglobulin G.
*
GMC ratios and CIs are calculated using the t-distribution with the variance estimate from a serotype-specific linear model utilizing the natural log-transformed antibody concentrations as the response and a single term for vaccination group.
A conclusion of non-inferiority of VAXNEUVANCE to Prevnar 13 is based on the lower bound of the 2-sided 95% CI for the GMC ratio (VAXNEUVANCE/Prevnar 13) being >0.5.
A conclusion of non-inferiority of VAXNEUVANCE to Prevnar 13 is based on the comparison of the GMC for the 2 additional serotypes to the lowest responding Prevnar 13 serotype (serotype 4), excluding serotype 3.
Serotype
1 1.21 1.82 0.66 (0.60, 0.73)
3 0.91 0.63 1.43 (1.30, 1.57)
4 1.07 1.42 0.76 (0.68, 0.84)
5 2.21 3.47 0.64 (0.57, 0.71)
6A 3.56 5.93 0.60 (0.54, 0.67)
6B 4.70 6.07 0.77 (0.69, 0.87)
7F 3.22 4.65 0.69 (0.62, 0.77)
9V 2.18 2.86 0.76 (0.69, 0.84)
14 5.09 6.21 0.82 (0.72, 0.93)
18C 2.37 2.59 0.92 (0.82, 1.02)
19A 3.86 4.93 0.78 (0.71, 0.86)
19F 3.32 4.02 0.83 (0.75, 0.91)
23F 1.85 2.88 0.64 (0.57, 0.72)
Additional Serotypes
22F 6.76 4.77 (4.28, 5.32)
33F 3.80 2.68 (2.40, 3.00)

Additionally, IgG response rates and IgG GMCs at 30 days postdose 3 and IgG GMCs at 30 days postdose 4 were statistically significantly greater for VAXNEUVANCE compared to Prevnar 13 for serotype 3 and the 2 unique serotypes (22F, 33F).

Serotype-specific OPA GMTs and response rates at 30 days postdose 3 and OPA GMTs at 30 days postdose 4 were descriptively evaluated in a subset of participants in Study 8. Serotype specific OPA GMTs and response rates were numerically similar across groups for the 13 shared serotypes and higher in the VAXNEUVANCE group for the 2 unique serotypes.

Children Receiving VAXNEUVANCE to Complete a 4-Dose Series Initiated with Prevnar 13

In a double-blind, active comparator-controlled, descriptive study (Study 9), participants were randomized in a 1:1:1:1:1 ratio to one of five vaccination groups. Two vaccination groups received a 4-dose series composed entirely of either VAXNEUVANCE (N=180) or Prevnar 13 (N=179). The remaining 3 study groups received either 1, 2, or 3 doses of Prevnar 13 followed by VAXNEUVANCE to complete the 4-dose series (N=180, 180, and 181, respectively). Participants also received other pediatric vaccines concomitantly [see Adverse Reactions (6.1) and Clinical Studies (14.3)]. Serotype-specific IgG GMCs for the 13 shared serotypes at 30 days postdose 4 were numerically similar for participants completing the vaccination series with VAXNEUVANCE compared to participants who received a complete series with Prevnar 13.

Children and Adolescents Receiving Catch-Up Vaccination

In a double-blind, active comparator-controlled, descriptive study (Study 12), participants were enrolled in three age cohorts (7 through 11 months of age, 12 through 23 months of age, and 2 through 17 years of age) and randomized to receive VAXNEUVANCE (N=303) or Prevnar 13 (N=303). Children in the two youngest age cohorts were pneumococcal vaccine-naïve at enrollment. Children in the oldest age cohort (2 through 17 years of age) were either pneumococcal vaccine naïve, not fully vaccinated, or had completed a dosing regimen with a lower valency pneumococcal conjugate vaccine (excluding Prevnar 13). Participants who were pneumococcal vaccine-naïve at enrollment received 1 to 3 doses of VAXNEUVANCE or Prevnar 13, depending on age at enrollment and according to the schedule shown in Table 1. All participants 2 through 17 years of age received one dose of VAXNEUVANCE. Catch-up vaccination with VAXNEUVANCE elicited immune responses, as assessed by serotype-specific IgG GMCs at 30 days following the last dose of vaccine, in children 7 months through 17 years of age that were numerically similar to Prevnar 13 for the shared serotypes and higher than Prevnar 13 for the unique serotypes 22F and 33F. Within each age cohort, serotype-specific IgG GMCs at 30 days following the last dose of vaccine were numerically similar between the vaccination groups for the 13 shared serotypes and higher in VAXNEUVANCE for the 2 unique serotypes.

VxLabels.com provides trustworthy package insert and label information about marketed drugs and vaccines as submitted by manufacturers to the U.S. Food and Drug Administration. Package information is not reviewed or updated separately by VxLabels.com. Every individual vaccine label and package insert entry contains a unique identifier which can be used to secure further details directly from the U.S. National Institutes of Health and/or the FDA.

Vaccine Sections

Vaccine Information by RSS

As the leading independent provider of trustworthy vaccine information, our database comes directly from the FDA's central repository of drug labels and package inserts under the Structured Product Labeling standard. VxLabels.com provides the full vaccine subset of the FDA's repository. Vaccine information provided here is not intended as a substitute for direct consultation with a qualified health professional.

Terms of Use | Copyright © 2022. All Rights Reserved.