FDA Label for Vaxneuvance

1 Indications And Usage

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 adults 18 years of age and older.

2 Dosage And Administration

For intramuscular use only.

2.1 Dosage

Administer a single 0.5 mL dose.

2.2 Administration

Hold the prefilled syringe horizontally and shake vigorously immediately prior to use to obtain an opalescent suspension in the prefilled syringe. 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. Do not use if particulate matter or discoloration is observed.

3 Dosage Forms And Strengths

VAXNEUVANCE is a suspension for intramuscular injection supplied in a 0.5 mL single-dose prefilled syringe.

4 Contraindications

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 (11).]

5.1 Altered Immunocompetence

Some individuals with altered immunocompetence, including those receiving immunosuppressive therapy, may have a reduced immune response to VAXNEUVANCE. [See Drug Interactions (7.1) and Use in Specific Populations (8.6).]

6.1 Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

The most commonly reported solicited adverse reactions in individuals 18 through 49 years of age were: injection-site pain (75.8%), fatigue (34.3%), myalgia (28.8%), headache (26.5%), injection-site swelling (21.7%), injection-site erythema (15.1%) and arthralgia (12.7%).

The most commonly reported solicited adverse reactions in individuals 50 years of age and older were: injection-site pain (66.8%), myalgia (26.9%), fatigue (21.5%), headache (18.9%), injection-site swelling (15.4%), injection-site erythema (10.9%) and arthralgia (7.7%).

Safety Assessment in Clinical Studies

The safety of VAXNEUVANCE was assessed in 7 randomized, double-blind clinical studies conducted in the Americas, Europe and Asia Pacific, in which 5,630 adults 18 years of age and older received VAXNEUVANCE and 1,808 adults received Prevnar 13 [Pneumococcal 13-valent Conjugate Vaccine (Diphtheria CRM₁₉₇ Protein)]. In Studies 1-3 (NCT03950622, NCT03950856, and NCT03480763), a total of 3,032 adults 50 years of age and older with no history of pneumococcal vaccination received VAXNEUVANCE and 1,154 participants received Prevnar 13. In Study 4 (NCT03547167), adults 18 through 49 years of age with no history of pneumococcal vaccination, including individuals with increased risk of developing pneumococcal disease, received VAXNEUVANCE (N=1,134) or Prevnar 13 (N=378), followed by PNEUMOVAX 23 six months later. In Study 5 (NCT02573181), adults 65 years of age and older previously vaccinated with PNEUMOVAX 23 (at least 1 year prior to study entry) received VAXNEUVANCE (N=127) or Prevnar 13 (N=126). In Study 6 (NCT03615482), adults 50 years of age and older received VAXNEUVANCE concomitantly with a seasonal inactivated quadrivalent influenza vaccine (Fluarix Quadrivalent; QIV) (Group 1, N=600) or nonconcomitantly 30 days after QIV (Group 2, N=585). In this study population, 20.9% of individuals had a history of prior vaccination with PNEUMOVAX 23. In Study 7 (NCT03480802), HIV-infected adults 18 years of age and older received VAXNEUVANCE (N=152) or Prevnar 13 (N=150), followed by PNEUMOVAX 23 two months later.

The clinical studies 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 behavioral risk factors (e.g., smoking, increased alcohol use) that are known to increase the risk of pneumococcal disease. Overall, the mean age of the participants was 58 years and 54.6% were female. The racial distribution was as follows: 72.3% were White, 9.9% were Asian, 8.1% were American Indian or Alaska Native, 7.4% were Black or African American, and 18.1% were of Hispanic or Latino ethnicity.

In all studies, safety was monitored using a Vaccination Report Card (VRC) for up to 14 days postvaccination. Study investigators reviewed the VRC with the participants 15 days postvaccination to ensure consistency with protocol definitions. The analyses presented in Tables 1-3 below reflect the information based on the final assessment by the study investigators. Oral body temperature and injection-site adverse reactions were solicited on Day 1 through Day 5 postvaccination. Systemic adverse reactions were solicited on Day 1 through Day 14 postvaccination. Unsolicited adverse events were reported on Day 1 through Day 14 postvaccination.

The duration of the safety follow-up period for serious adverse events postvaccination with VAXNEUVANCE was 1 month in Study 5; 2 months in Study 7; 6 months in Studies 1, 2, 4 and 6; and 12 months in Study 3.

Solicited Adverse Reactions

The percentage of participants with solicited adverse reactions that occurred within 5 or 14 days following administration of VAXNEUVANCE or Prevnar 13 in 3 studies are shown in Tables 1-3. The majority of solicited adverse reactions lasted ≤3 days.

Unsolicited Adverse Reactions

Across all studies, injection-site pruritus was reported to occur in up to 2.8% of adults vaccinated with VAXNEUVANCE.

Serious Adverse Events

Across all studies, among participants 18 years of age and older who received VAXNEUVANCE (excluding those who received QIV concomitantly; N=5,030) or Prevnar 13 (N=1,808), serious adverse events within 30 days postvaccination were reported by 0.4% of VAXNEUVANCE recipients and by 0.7% of Prevnar 13 recipients. In a subset of these studies, among those who received VAXNEUVANCE (N=4,751) and Prevnar 13 (N=1,532), serious adverse events within 6 months postvaccination were reported by 2.5% of VAXNEUVANCE recipients and by 2.4% of Prevnar 13 recipients.

There were no notable patterns or numerical imbalances between vaccination groups for specific categories of serious adverse events that would suggest a causal relationship to VAXNEUVANCE.

Safety with Concomitant Influenza Vaccine Administration

The safety profile was similar when VAXNEUVANCE was administered with or without inactivated quadrivalent influenza vaccine.

7.1 Immunosuppressive Therapies

Immunosuppressive therapies may reduce the immune response to this vaccine [see Warnings and Precautions (5.1)].

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 in individuals younger than 18 years 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

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 between the two vaccination groups. The effectiveness of VAXNEUVANCE in HIV-infected individuals has not been evaluated.

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.

12.1 Mechanism Of Action

Protection against invasive disease is conferred mainly by opsonophagocytic killing of S. pneumoniae. VAXNEUVANCE induces opsonophagocytic activity against the serotypes contained in the vaccine.

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 were measured by a multiplexed opsonophagocytic antibody assay (MOPA) for the 15 pneumococcal serotypes contained in VAXNEUVANCE pre- and post- vaccination.

14.1 Clinical Trials In Pneumococcal Vaccine-Naïve Adults

Study 1

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 vaccine-naïve 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 4 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).

Study 3

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.

Study 4

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 (6.1)]. Among those who received VAXNEUVANCE, 620 participants had one risk factor and 228 participants had two or more risk factors for pneumococcal disease.

Table 5 presents OPA GMTs in the overall study population for each of the 15 serotypes 30 days following vaccination with VAXNEUVANCE or Prevnar 13.

Following vaccination with PNEUMOVAX 23, the OPA GMTs for the 15 serotypes in VAXNEUVANCE were numerically similar among subjects who had received VAXNEUVANCE or Prevnar 13 for the first vaccination.

14.2 Concomitant Vaccination

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 (6)]. 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.

16 How Supplied/Storage And Handling

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

Storage And Handling

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.

17 Patient Counseling Information

Advise the patient to read the FDA-approved patient labeling (Patient Information).

Discuss the following with the patient:

• Provide the required vaccine information to the patient.
• Inform the patient of the benefits and risks associated with vaccination.
• Inform the patient that vaccination with VAXNEUVANCE may not protect all vaccine recipients.
• Instruct the patient to report any serious adverse reactions to their healthcare provider who in turn should report such events to the vaccine manufacturer or the U.S. Department of Health and Human Services through the Vaccine Adverse Event Reporting System (VAERS), 1-800-822-7967, or report online at www.vaers.hhs.gov.

Principal Display Panel - 0.5 Ml Syringe Carton

NDC 0006-4329-03
10 Single-dose 0.5 mL Syringes

REFRIGERATE

Pneumococcal 15-valent
Conjugate Vaccine
VAXNEUVANCE™

Suspension for intramuscular injection

For use in individuals 18 years of age and older

Rx only

Each 0.5 mL dose contains 2.0 mcg each of Streptococcus 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,
and 125 mcg of aluminum as aluminum phosphate adjuvant.
Contains no preservative.

Principal Display Panel - 0.5 mL Syringe Carton - vaxneuvance 01