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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.
VAXNEUVANCE® is indicated for active immunization for the prevention of invasive disease caused by Streptococcus pneumoniae serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, 22F, 23F and 33F in individuals 6 weeks of age and older.
For intramuscular injection only.
Each dose of VAXNEUVANCE is 0.5 mL.
Hold the prefilled syringe horizontally and shake vigorously immediately prior to use to obtain an opalescent suspension. Do not use the vaccine if it cannot be resuspended. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Do not use if particulate matter or discoloration is observed.
Administer VAXNEUVANCE as a 4-dose series at 2, 4, 6 and 12 through 15 months of age (and at least 2 months after the third dose). The first dose may be given as early as 6 weeks of age.
The 4-dose series initiated with a lower valency pneumococcal conjugate vaccine can be completed with VAXNEUVANCE [see Clinical Studies].
Administer VAXNEUVANCE as a single dose in adults 18 years of age and older.
Children 7 months through 17 years of age who have never received a pneumococcal conjugate vaccine may receive VAXNEUVANCE according to the schedule in Table 1:
Table 1: Catch-Up Vaccination Schedule for Individuals Initiating Vaccination at 7 Months Through 17 Years of Age
| Age at First Dose | Total Number of 0.5 mL Doses |
| 7 through 11 months of age | 3* |
| 12 through 23 months of age | 2† |
| 2 years through 17 years of age | 1 |
| *The first 2 doses are given at least 4 weeks apart; third dose given after the one-year birthday, separated from the second dose by at least 2 months. †Two doses at least 2 months apart. |
|
Administer a single dose of VAXNEUVANCE to children and adolescents 2 years through 17 years of age who have received an incomplete series of another pneumococcal conjugate vaccine. At least 2 months should elapse between receipt of the last dose of another pneumococcal conjugate vaccine and administration of VAXNEUVANCE.
VAXNEUVANCE is a suspension for intramuscular injection supplied in a 0.5 mL singledose prefilled syringe.
VAXNEUVANCE is supplied as follows:
Carton of one 0.5 mL single-dose prefilled Luer Lock syringes with tip caps. NDC 0006- 4329-02
Carton of ten 0.5 mL single-dose prefilled Luer Lock syringes with tip caps. NDC 0006- 4329-03
Store refrigerated at 2°C to 8°C (36°F to 46°F).
Do not freeze. Protect from light.
The tip cap and plunger stopper of the prefilled syringe are not made with natural rubber latex.
Manufactured by: Merck Sharp & Dohme LLC, Rahway, NJ 07065, USA. Revised: May 2024
Included as part of the "PRECAUTIONS" Section
Appropriate medical treatment to manage allergic reactions must be immediately available in the event an acute anaphylactic reaction occurs following administration of VAXNEUVANCE.
Some individuals with altered immunocompetence, including those receiving immunosuppressive therapy, may have a reduced immune response to VAXNEUVANCE. [see Use In Specific Populations]
Apnea following intramuscular vaccination has been observed in some infants born prematurely. A decision about when to administer VAXNEUVANCE to infants born prematurely should be based on consideration of the individual infant’s medical status and the potential benefits and possible risks of vaccination.
Advise the patient, parent or guardian to read the FDA-approved patient labeling (PATIENT INFORMATION).
Discuss the following with the patient, parent or guardian:
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].
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].
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.
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.
The safety and effectiveness of VAXNEUVANCE have been established in individuals 6 weeks through 17 years of age [see ADVERSE REACTIONS and Clinical Studies]. The safety and effectiveness of VAXNEUVANCE in individuals younger than 6 weeks of age have not been established.
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 and Clinical Studies]. 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.
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.
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.
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]. 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.
In a double-blind, descriptive study (Study 15, NCT03565900), the safety and immunogenicity of VAXNEUVANCE compared to Prevnar 13 were evaluated in participants who had received an allogeneic hematopoietic stem cell transplant (allo- HSCT) 3 to 6 months prior to enrollment. All participants had a history of stable engraftment and none had severe graft-versus-host disease. In this study, participants were randomized to receive 3 doses of VAXNEUVANCE (N=139) or Prevnar 13 (N=138), administered one month apart. Among those participants 3 through 17 years of age, 8 participants received VAXNEUVANCE and 6 participants received Prevnar 13. The remaining participants were 18 through 74 years of age. Twelve months after allo- HSCT, participants without chronic graft-versus-host disease (cGVHD) received a single dose of PNEUMOVAX 23 (N=164) and those with cGVHD received a fourth consecutive dose of VAXNEUVANCE (N=29) or Prevnar 13 (N=37). IgG GMCs and OPA GMTs were higher after administration of 3 doses of VAXNEUVANCE, compared to pre-vaccination, for the 15 serotypes contained in VAXNEUVANCE. Serotype-specific IgG GMCs and OPA GMTs were numerically similar between the two vaccination groups for the 13 shared serotypes and higher in VAXNEUVANCE for the two unique serotypes (22F and 33F).
Similarly, in participants who received VAXNEUVANCE or Prevnar 13 twelve months after allo-HSCT, IgG GMCs and OPA GMTs at 30 days following vaccination were numerically similar between the two vaccination groups for the 13 shared serotypes and higher in VAXNEUVANCE for the two unique serotypes (22F and 33F). In participants who received PNEUMOVAX 23 twelve months after allo-HSCT, IgG GMCs and OPA GMTs at 30 days following vaccination were numerically similar between those who had received either 3 doses of VAXNEUVANCE or Prevnar 13 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 recipients of allo-HSCT has not been established.
No Information Provided
Do not administer VAXNEUVANCE to individuals with a severe allergic reaction (e.g., anaphylaxis) to any component of VAXNEUVANCE or to diphtheria toxoid. [See DESCRIPTION.]
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.
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.
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 and Concomitant Vaccination.]
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)
| Pneumococcal Serotype | VAXNEUVANCE (n=452-455) |
Prevnar 13 (n=426-430) |
Percentage Point Difference (VAXNEUVANCE – Prevnar 13) (95% CI)*, † |
| Observed Response Percentage | Observed Response Percentage | ||
| 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) |
| n=Number of participants contributing to the analysis. CI=Confidence interval; IgG=Immunoglobulin G *CIs are based on the Miettinen & Nurminen method. †Aconclusion 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. |
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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)
| Pneumococcal Serotype |
VAXNEUVANCE (n=452-455) |
Prevnar 13 (n=426-430) |
GMC Ratio* (VAXNEUVANCE /Prevnar 13) (95% CI)*, † |
| GMC | GMC | ||
| 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) |
| 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 |
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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)
| Pneumococcal Serotype |
VAXNEUVANCE (n=466-470) |
Prevnar 13 (n=443- 447) |
GMC Ratio* (VAXNEUVANCE/ Prevnar 13) (95% CI)*, † |
| GMC | GMC | ||
| 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) |
| 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. |
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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.
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 and Concomitant Vaccination]. 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.
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 vaccinenaïve 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.
Study 1 assessed serotype-specific opsonophagocytic activity (OPA) responses for each of the 15 serotypes contained in VAXNEUVANCE at 30 days postvaccination in a double-blind, active comparator-controlled study that enrolled pneumococcal vaccinenaïve participants 50 years of age and older. Participants were randomized to receive either VAXNEUVANCE (N=604) or Prevnar 13 (N=601) at sites in USA, Canada, Spain, Taiwan, and Japan. The mean age of participants was 66 years and 57.3% were female. The racial distribution was as follows: 67.7% were White, 25.1% were Asian, 6.1% were Black or African American and 22.0% were of Hispanic or Latino ethnicity.
Table 12 summarizes the OPA geometric mean antibody titers (GMTs) at 30 days postvaccination for the 15 serotypes contained in VAXNEUVANCE. The study demonstrated that VAXNEUVANCE is noninferior to Prevnar 13 for the 13 shared serotypes and induces statistically significantly greater OPA GMTs compared to Prevnar 13 for shared serotype 3 and for the 2 unique serotypes (22F, 33F).
Table 12: Serotype-Specific OPA GMTs in Pneumococcal Vaccine- Naïve Adults 50 Years of Age and Older (Study 1)
| Pneumococcal Serotype | VAXNEUVANCE (N = 602) |
Prevnar 13 (N = 600) |
GMT Ratio* (VAXNEUVANCE/ Prevnar 13) (95% CI)* |
||
| n | GMT* | n | GMT* | ||
| Serotype† | |||||
| 1 | 598 | 257 | 598 | 321 | 0.80 (0.66, 0.97) |
| 3‡ | 598 | 215 | 598 | 133 | 1.62 (1.40, 1.87) |
| 4 | 598 | 1109 | 598 | 1633 | 0.68 (0.57, 0.80) |
| 5 | 598 | 445 | 598 | 560 | 0.79 (0.64, 0.98) |
| 6A | 596 | 5371 | 596 | 5276 | 1.02 (0.85, 1.22) |
| 6B | 598 | 3984 | 598 | 3179 | 1.25 (1.04, 1.51) |
| 7F | 596 | 4575 | 596 | 5830 | 0.78 (0.68, 0.90) |
| 9V | 598 | 1809 | 597 | 2193 | 0.83 (0.71, 0.96) |
| 14 | 598 | 1976 | 598 | 2619 | 0.75 (0.64, 0.89) |
| 18C | 598 | 2749 | 598 | 2552 | 1.08 (0.91, 1.27) |
| 19A | 598 | 3177 | 597 | 3921 | 0.81 (0.70, 0.94) |
| 19F | 598 | 1688 | 598 | 1884 | 0.90 (0.77, 1.04) |
| 23F | 598 | 2029 | 598 | 1723 | 1.18 (0.96, 1.44) |
| Additional Serotypes§ | |||||
| 22F | 594 | 2381 | 585 | 73 | 32.52 (25.87, 40.88) |
| 33F | 598 | 8010 | 597 | 1114 | 7.19 (6.13, 8.43) |
| N=Number of participants randomized and vaccinated; n=Number of participants contributing to the analysis that had at least one pre-dose OPA measurement (VAXNEUVANCE, n=537-597; Prevnar 13, n=545-595) or post-dose OPA measurement (VAXNEUVANCE, n=568-580; Prevnar 13, n=528-574). CI=confidence interval; cLDA=constrained longitudinal data analysis; GMT=geometric mean titer; OPA=opsonophagocytic activity *GMTs, GMT ratio, and 95% CI are estimated from a cLDA model. †Non-inferiority for the 13 shared serotypes was met if the lower bound of the 95% CI for the GMT ratio (VAXNEUVANCE/Prevnar 13) was > 0.5. ‡Statistically significantly greater OPA GMT for serotype 3 was based on the lower bound of the 95% CI for the estimated GMT ratio (VAXNEUVANCE/Prevnar 13) > 1.2. §Statistically significantly greater OPA GMTs for serotypes 22F and 33F was based on the lower bound of the 95% CI for the estimated GMT ratio (VAXNEUVANCE/Prevnar 13) > 2.0. |
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In a double-blind, active comparator-controlled, descriptive study (Study 3), pneumococcal vaccine-naïve adults 50 years of age and older were randomized to receive either VAXNEUVANCE (N=327) or Prevnar 13 (N=325), followed by PNEUMOVAX 23 one year later.
Following vaccination with PNEUMOVAX 23, OPA GMTs were numerically similar between the two vaccination groups for the 15 serotypes in VAXNEUVANCE.
In a double-blind, descriptive study (Study 4), adults 18 through 49 years of age, including individuals with increased risk of developing pneumococcal disease, were randomized to receive VAXNEUVANCE (N=1,135) or Prevnar 13 (N=380), followed by PNEUMOVAX 23 six months later [see ADVERSE REACTIONS]. Among those who received VAXNEUVANCE, 620 participants had one risk factor and 228 participants had two or more risk factors for pneumococcal disease.
Table 13 presents OPA GMTs in the overall study population for each of the 15 serotypes 30 days following vaccination with VAXNEUVANCE or Prevnar 13.
Table 13: Serotype-Specific OPA GMTs in Pneumococcal VaccineNaïve Adults 18 through 49 Years of Age With or Without Risk Factors for Pneumococcal Disease (Study 4)
| Pneumococcal Serotype | VAXNEUVANCE (N = 602) |
Prevnar 13 (N = 600) |
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| n | Observed GMT |
95% CI* | n | Observed GMT |
95% CI* | ||
| 1 | 1004 | 267 | (242, 295) | 337 | 267 | (220, 324) | |
| 3 | 990 | 198 | (184, 214) | 336 | 150 | (129, 173) | |
| 4 | 1001 | 1401 | (1294, 1517) | 338 | 2568 | (2268, 2908) | |
| 5 | 1003 | 560 | (508, 618) | 339 | 731 | (613, 873) | |
| 6A | 994 | 12763 | (11772, 13838) | 333 | 11313 | (9739, 13141) | |
| 6B | 999 | 10164 | (9486, 10891) | 338 | 6958 | (5987, 8086) | |
| 7F | 1004 | 5725 | (5382, 6090) | 338 | 7583 | (6762, 8503) | |
| 9V | 1000 | 3353 | (3132, 3590) | 339 | 3969 | (3541, 4449) | |
| 14 | 1001 | 5245 | (4860, 5660) | 339 | 5863 | (5191, 6623) | |
| 18C | 999 | 5695 | (5314, 6103) | 339 | 3050 | (2685, 3465) | |
| 19A | 1001 | 5335 | (4985, 5710) | 339 | 5884 | (5221, 6632) | |
| 19F | 1003 | 3253 | (3051, 3468) | 339 | 3272 | (2949, 3631) | |
| 23F | 1001 | 4828 | (4443, 5247) | 337 | 3876 | (3323, 4521) | |
| Additional Serotypes | |||||||
| 22F | 991 | 3939 | (3654, 4246) | 317 | 291 | (221, 383) | |
| 33F | 999 | 11734 | (10917,12612) | 334 | 2181 | (1826, 2606) | |
| N=Number of participants randomized and vaccinated; n=Number of participants contributing to the analysis. CI=confidence interval; GMT=geometric mean titer; OPA=opsonophagocytic activity. *The within-group 95% CIs are obtained by exponentiating the CIs of the mean of the natural log values based on the t-distribution |
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Following vaccination with PNEUMOVAX 23, the OPA GMTs for the 15 serotypes in VAXNEUVANCE were numerically similar among participants who had received VAXNEUVANCE or Prevnar 13 for the first vaccination.
In Study 8, the concomitant administration of Pentacel with each of the 3 infant doses of either VAXNEUVANCE (N=598) or Prevnar 13 (N=601) was evaluated 30 days following the third dose; concomitant administration of single doses of VAQTA, M-M-R II, VARIVAX and Hiberix with the fourth dose of either VAXNEUVANCE or Prevnar 13 was evaluated 30 days following vaccination. There was no evidence that VAXNEUVANCE, as compared to Prevnar 13, interfered with the immune responses to these concomitantly administered vaccines. The immune responses to the antigens in Pentacel following completion of the 4-dose series were not evaluated.
In Study 9, the concomitant administration of RECOMBIVAX HB with either VAXNEUVANCE (N=124) or Prevnar 13 (N=266) was evaluated 30 days following the third dose of pneumococcal conjugate vaccine. Most infants (97.2%) received a birth dose of hepatitis B vaccine, followed by two doses of RECOMBIVAX HB administered concomitantly with VAXNEUVANCE or Prevnar 13. There was no evidence that VAXNEUVANCE, as compared to Prevnar 13, interfered with the immune response to RECOMBIVAX HB.
In a double-blind, randomized study (Study 6), adults 50 years of age and older were randomized to receive VAXNEUVANCE concomitantly administered with a seasonal inactivated quadrivalent influenza vaccine (Fluarix Quadrivalent; QIV) (Group 1, N=600) or VAXNEUVANCE 30 days after receiving QIV (Group 2, N=600) [see ADVERSE REACTIONS]. Pneumococcal vaccine serotype OPA GMTs were evaluated 30 days after VAXNEUVANCE and influenza vaccine strain hemagglutinin inhibition assay (HAI) GMTs were evaluated 30 days after QIV. The noninferiority criteria for the comparisons of GMTs [lower limit of the 2-sided 95% confidence interval (CI) of the GMT ratio (Group 1/Group 2) >0.5] were met for the 15 pneumococcal serotypes in VAXNEUVANCE and for the 4 influenza vaccine strains tested.
VAXNEUVANCE ®
(pronounced “VAKS-noo-vans”)
(Pneumococcal 15-valent Conjugate Vaccine)
Before you get VAXNEUVANCE ®, read this information sheet and be sure you understand it. If you have questions or experience any side effects, talk to your healthcare provider. This information does not take the place of talking about VAXNEUVANCE with your healthcare provider. Your healthcare provider will decide if VAXNEUVANCE is right for you or your child.
What is VAXNEUVANCE?
Who should not get VAXNEUVANCE?
Do not get VAXNEUVANCE if you or your child:
What should I tell my healthcare provider before getting VAXNEUVANCE?
Tell your healthcare provider if you or your child:
If your child is an infant, also tell your healthcare provider if your child was born too early (prematurely).
How is VAXNEUVANCE given?
VAXNEUVANCE is given as an injection into the muscle (usually in the upper arm for adults and the upper arm or thigh for children).
Children need 4 doses of the vaccine:
If your child did not receive the complete series according to this schedule, your healthcare provider may suggest a catch-up schedule.
Your child may get VAXNEUVANCE at the same time they get other vaccines.
Adults need one dose of the vaccine.
What are the possible side effects of VAXNEUVANCE?
The most common side effects seen with VAXNEUVANCE in children less than 2 years of age are:
The most common side effects seen with VAXNEUVANCE in children and adolescents 2 through 17 years of age are:
The most common side effects seen with VAXNEUVANCE in adults 18 years of age and older are:
In most people these side effects went away within three days.
If you or your child have any side effects that become bothersome or any other unusual symptoms that develop after getting this injection, tell your healthcare provider. Tell your healthcare provider right away if you or your child have symptoms of an allergic reaction which may include:
There may be side effects that are not listed here. For more information, ask your healthcare provider.
You may also report any side effects to Merck Sharp & Dohme LLC at 1-877-888-4231 or directly to Vaccine Adverse Event Reporting System (VAERS). The VAERS toll-free number is 1-800-822-7967 or report online to www.vaers.hhs.gov .
What are the ingredients in VAXNEUVANCE?
Active ingredient: Bacterial sugars from 15 types of pneumococcus each linked to a protein (CRM ). The sugars from these bacteria and the protein are not alive and do not cause disease.
Inactive ingredients: Sodium chloride, L-histidine, polysorbate 20 and aluminum (aluminum phosphate is included to help the vaccine work better).
VAXNEUVANCE does not have any preservatives.
The tip cap and plunger stopper of the prefilled syringe are not made with natural rubber latex.
What if I have other questions?
If you have questions about VAXNEUVANCE, talk to your healthcare provider or call 1- 800-622-4477.
This Patient Information has been approved by the U.S. Food and Drug Administration.
