PENBRAYA- meningococcal groups a, b, c, w, and y vaccine kit

PENBRAYA by

Drug Labeling and Warnings

PENBRAYA by is a Other medication manufactured, distributed, or labeled by Pfizer Laboratories Div Pfizer Inc, Pfizer Health AB, Pfizer Inc, Wyeth Pharmaceutical Division of Wyeth Holdings LLC, Pfizer Ireland Pharmaceuticals, Pfizer Manufacturing Austria GmbH, Pfizer Manufacturing Belgium NV. Drug facts, warnings, and ingredients follow.

Drug Details [pdf]

• HIGHLIGHTS OF PRESCRIBING INFORMATION

  These highlights do not include all the information needed to use PENBRAYA safely and effectively. See full prescribing information for PENBRAYA.
  
  PENBRAYA® (Meningococcal Groups A, B, C, W, and Y Vaccine), suspension for intramuscular injection
  Initial U.S. Approval: 2023

  INDICATIONS AND USAGE

  PENBRAYA is indicated for active immunization to prevent invasive disease caused by Neisseria meningitidis serogroups A, B, C, W, and Y. PENBRAYA is approved for use in individuals 10 through 25 years of age. (1)

  DOSAGE AND ADMINISTRATION

  • For intramuscular use only. (2)
  • Administer 2 doses (approximately 0.5 mL each) of PENBRAYA 6 months apart. (2.1)
  • To prepare PENBRAYA, reconstitute the Lyophilized MenACWY Component with the MenB Component. (2.2)

  DOSAGE FORMS AND STRENGTHS

  PENBRAYA is a suspension for injection. A single dose after reconstitution is approximately 0.5 mL. (3)

  CONTRAINDICATIONS

  Severe allergic reaction (e.g., anaphylaxis) to any component of PENBRAYA. (4)

  ADVERSE REACTIONS

  The most commonly reported (≥15%) solicited adverse reactions after Dose 1 and Dose 2, respectively, were pain at the injection site (89% and 84%), fatigue (52% and 48%), headache (47% and 40%), muscle pain (26% and 23%), injection site redness (26% and 23%), injection site swelling (25% and 24%), joint pain (20% and 18%), and chills (20% and 16%). (6)
  
  

  To report SUSPECTED ADVERSE REACTIONS, contact Pfizer Inc. at 1-800-438-1985 or VAERS at 1-800-822-7967 or http://vaers.hhs.gov.

  See 17 for PATIENT COUNSELING INFORMATION.

  Revised: 11/2024

• Table of Contents

  FULL PRESCRIBING INFORMATION: CONTENTS*

  1 INDICATIONS AND USAGE

  2 DOSAGE AND ADMINISTRATION

  2.1 Dose and Schedule

  2.2 Preparation

  2.3 Administration

  3 DOSAGE FORMS AND STRENGTHS

  4 CONTRAINDICATIONS

  5 WARNINGS AND PRECAUTIONS

  5.1 Management of Acute Allergic Reactions

  5.2 Syncope

  5.3 Altered Immunocompetence

  5.4 Limitations of Vaccine Effectiveness

  5.5 Tetanus Immunization

  5.6 Guillain-Barré Syndrome

  6 ADVERSE REACTIONS

  6.1 Clinical Trials Experience

  6.2 Postmarketing Experience

  8 USE IN SPECIFIC POPULATIONS

  8.1 Pregnancy

  8.2 Lactation

  8.4 Pediatric Use

  8.5 Geriatric Use

  11 DESCRIPTION

  12 CLINICAL PHARMACOLOGY

  12.1 Mechanism of Action

  13 NONCLINICAL TOXICOLOGY

  13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

  14 CLINICAL STUDIES

  14.1 Immunogenicity

  15 REFERENCES

  16 HOW SUPPLIED/STORAGE AND HANDLING

  16.1 How Supplied

  16.2 Storage Before Reconstitution

  16.3 Storage After Reconstitution

  17 PATIENT COUNSELING INFORMATION

  * Sections or subsections omitted from the full prescribing information are not listed.

1 INDICATIONS AND USAGE

PENBRAYA is indicated for active immunization to prevent invasive disease caused by Neisseria meningitidis serogroups A, B, C, W, and Y. PENBRAYA is approved for use in individuals 10 through 25 years of age.

2 DOSAGE AND ADMINISTRATION

For intramuscular use only.

2.1 Dose and Schedule

Administer 2 doses (approximately 0.5 mL each) of PENBRAYA 6 months apart.

2.2 Preparation

PENBRAYA is supplied in a kit that includes a vial of Lyophilized MenACWY Component (a sterile white powder), a prefilled syringe containing the MenB Component and a vial adapter.

To form PENBRAYA, reconstitute the Lyophilized MenACWY Component with the MenB Component as described in the instructions below.

2.3 Administration

For intramuscular use only.

After reconstitution, PENBRAYA is a homogeneous white suspension. If the vaccine is not a homogenous suspension, shake to resuspend prior to administration. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Discard if either condition is present.

Administer PENBRAYA immediately or store between 2°C and 30°C (36°F and 86°F) and use within 4 hours. Discard reconstituted vaccine if not used within 4 hours.

3 DOSAGE FORMS AND STRENGTHS

PENBRAYA is a suspension for injection.

A single dose after reconstitution is approximately 0.5 mL.

4 CONTRAINDICATIONS

Do not administer PENBRAYA to individuals with a history of severe allergic reaction (e.g., anaphylaxis) to any component of PENBRAYA [see Description (11)].

5 WARNINGS AND PRECAUTIONS

5.1 Management of Acute Allergic Reactions

Appropriate medical treatment used to manage immediate allergic reactions must be immediately available in the event an anaphylactic reaction occurs following administration of PENBRAYA.

5.2 Syncope

Syncope (fainting) may occur in association with administration of injectable vaccines, including PENBRAYA. Procedures should be in place to avoid injury from fainting.

5.3 Altered Immunocompetence

Reduced Immune Response

Some individuals with altered immunocompetence may have reduced immune responses to PENBRAYA.

Complement Deficiency

Individuals with certain complement deficiencies and individuals receiving treatment that inhibits terminal complement activation are at increased risk for invasive disease caused by N. meningitidis groups A, B, C, W, and Y, even if they develop antibodies following vaccination with PENBRAYA [see Clinical Pharmacology (12.1)].

5.4 Limitations of Vaccine Effectiveness

Vaccination with PENBRAYA may not protect all vaccine recipients.

5.5 Tetanus Immunization

Vaccination with PENBRAYA does not substitute for vaccination with a tetanus toxoid containing vaccine to prevent tetanus.

5.6 Guillain-Barré Syndrome

Guillain-Barré syndrome (GBS) has been reported in temporal relationship following administration of another U.S.-licensed meningococcal quadrivalent polysaccharide conjugate vaccine. The decision by the healthcare professional to administer PENBRAYA to persons with a history of GBS should take into account the expected benefits and potential risks.

6 ADVERSE REACTIONS

The most commonly reported (≥15%) solicited adverse reactions after Dose 1 and Dose 2, respectively, were pain at the injection site (89% and 84%), fatigue (52% and 48%), headache (47% and 40%), muscle pain (26% and 23%), injection site redness (26% and 23%), injection site swelling (25% and 24%), joint pain (20% and 18%), and chills (20% and 16%).

6.1 Clinical Trials Experience

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

The safety of PENBRAYA in individuals 10 through 25 years of age was evaluated in 3 clinical studies (2 active-controlled and 1 non-controlled study). In the controlled studies, 2306 participants received at least 1 dose of PENBRAYA. Of 946 participants who had previously received a meningococcal conjugate vaccine (categorized as MenACWY conjugate vaccine-exposed), 802 participants had received 1 dose of any U.S.-licensed Meningococcal Groups A, C, W, and Y conjugate vaccine, 51 participants had received a non-U.S.-licensed monovalent Meningococcal Group C conjugate vaccine (MenC conjugate vaccine), and 93 participants had received an unspecified U.S.-licensed or non-U.S.-licensed MenACWY conjugate or a MenC conjugate vaccine at least 4 years prior to enrollment. In the non-controlled study, 300 participants received a single dose of PENBRAYA.

Study 1 (NCT04440163) was an active-controlled, observer-blinded, multicenter study in which participants 10 through 25 years of age in the U.S. and Europe received at least 1 dose of PENBRAYA (N=1763) or Meningococcal Group B Vaccine (Trumenba) (N=650) at 0 and 6 months. Meningococcal Groups A, C, Y, and W-135 Oligosaccharide Diphtheria CRM197 Conjugate Vaccine (MenACWY-CRM, GSK Vaccines, SRL) was concomitantly administered with Trumenba at Month 0. All participants were MenB vaccine-naïve. Both MenACWY conjugate vaccine-naïve and MenACWY conjugate vaccine-exposed participants were part of the study.

Study 2 (NCT03135834) was an active-controlled, observer-blinded, multicenter study in which participants 10 through 25 years of age in the U.S. and Europe received at least 1 dose of PENBRAYA (N=543) or Trumenba (N=1057) at 0 and 6 months. MenACWY-CRM was co-administered with Trumenba at Month 0. All participants were MenB vaccine-naïve. Both MenACWY conjugate vaccine-naïve and MenACWY conjugate vaccine-exposed participants were part of this study.

Study 3 (NCT04440176) was a descriptive non-controlled study in which participants 11 through 14 years of age in the U.S. received PENBRAYA 12 months apart. All participants were naïve to any meningococcal vaccine.

In Study 1 and Study 2, solicited local and systemic adverse reactions were monitored for 7 days after study vaccination using an electronic diary. In all studies, spontaneous reports of adverse events (AEs) were collected through at least 1 month after the last vaccination, and through 6 months after the last vaccination for serious adverse events (SAEs).

In controlled studies, demographic characteristics were generally similar with regard to gender, race, and ethnicity among participants who received PENBRAYA and those who received control (Trumenba and MenACWY-CRM). Among participants who received PENBRAYA in controlled studies, 47.4% were male, 79.4% were White, 10.2% were Black or African-American, 2.1% were Asian, and 2.6% were of other racial groups, and 21.6% were of Hispanic/Latino ethnicity.

Solicited Local and Systemic Adverse Reactions

Table 1 presents the solicited local adverse reactions and Table 2 presents the solicited systemic adverse reactions and use of antipyretic medication reported within 7 days following each dose of PENBRAYA in Study 1.

Table 1. Percentage of Participants Reporting Solicited Local Adverse Reactions Within 7 Days After PENBRAYA or Trumenba Vaccination in Study 1*

Abbreviations: N = number of participants; MenACWY-CRM = meningococcal (serogroups A, C, W and Y) oligosaccharide diphtheria CRM197 conjugate vaccine; Trumenba = meningococcal serogroup B factor H binding protein.
* NCT04440163 † Trumenba and MenACWY-CRM were administered at 0 month followed by Trumenba alone at 6 months. Local reactions were recorded only for PENBRAYA and Trumenba injection sites. ‡ Mild (does not interfere with activity); Moderate (interferes with activity); Severe (prevents daily activity). § "Any" is defined as the cumulative frequency of participants who reported a reaction as "mild", "moderate", or "severe" within 7 days of vaccination. ¶ Mild (2.0 to 5 cm); Moderate (>5 to 10 cm); Severe (>10 cm).
Injection Site Reactions	PENBRAYA		Trumenba + MenACWY-CRM†
	Dose 1	Dose 2	Dose 1	Dose 2
	N=1724-1725 %	N=1456 %	N=630-631 %	N=529 %
Pain‡
Any§	89.3	84.4	85.1	78.6
Mild	32.3	29.1	31.1	33.1
Moderate	49.4	48.8	47.7	40.3
Severe	7.5	6.5	6.3	5.3
Redness¶
Any§	25.9	23.2	19.5	14.7
Mild	8.9	7.7	7.3	6.6
Moderate	14.4	12.6	10.0	7.2
Severe	2.6	3.0	2.2	0.9
Swelling¶
Any§	25.0	24.2	21.4	14.7
Mild	10.6	10.4	8.3	6.4
Moderate	13.3	12.8	12.4	8.1
Severe	1.2	1.0	0.8	0.2

Table 2. Percentage of Participants Reporting Solicited Systemic Adverse Reactions and Use of Antipyretic Medications Within 7 Days After Each Vaccination in Study 1

Abbreviations: N = number of participants; MenACWY-CRM = meningococcal (serogroups A, C, W and Y) oligosaccharide diphtheria CRM197 conjugate vaccine; Trumenba= meningococcal serogroup B factor H binding protein.
* Trumenba and MenACWY-CRM were administered at 0 month followed by Trumenba alone at 6 months. † Mild (1 to 2 times in 24 hours); Moderate (>2 times in 24 hours); Severe (requires intravenous hydration). ‡ "Any" is defined as the cumulative frequency of participants who reported a reaction as "mild", "moderate", or "severe" within 7 days of vaccination. § Mild (2 to 3 loose stools in 24 hours); Moderate (4 to 5 loose stools in 24 hours); Severe (6 or more loose stools in 24 hours). ¶ Mild (does not interfere with activity); Moderate (interferes with activity); Severe (prevents daily activity).
Systemic Reactions	PENBRAYA		Trumenba + MenACWY-CRM*
	Dose 1	Dose 2	Dose 1	Dose 2
	N=1739-1740 %	N=1459 %	N=638 %	N=532 %
Fever (≥38°C)
≥38.0°C	5.9	2.4	5.8	1.5
38.0° to 38.4°C	3.7	1.9	2.0	0.4
>38.4° to 38.9°C	1.6	0.3	2.8	0.9
>38.9° to 40.0°C	0.6	0.2	0.9	0.2
>40.0°C	0.0	0.0	0.0	0.0
Vomiting†
Any‡	3.2	1.5	3.0	0.9
Mild	2.5	1.4	2.0	0.8
Moderate	0.6	0.1	0.9	0.2
Severe	0.0	0.0	0.0	0.0
Diarrhea§
Any‡	11.0	8.2	13.5	8.5
Mild	8.7	6.9	11.9	6.0
Moderate	2.0	1.4	1.6	2.4
Severe	0.3	0.0	0.0	0.0
Headache¶
Any‡	46.8	39.8	46.9	37.8
Mild	25.7	21.3	24.5	21.1
Moderate	19.2	16.8	20.4	16.2
Severe	1.9	1.7	2.0	0.6
Fatigue¶
Any‡	52.1	47.6	54.7	43.6
Mild	23.5	22.8	25.7	22.0
Moderate	25.5	21.8	25.7	19.9
Severe	3.2	2.9	3.3	1.7
Chills¶
Any‡	20.1	16.4	19.6	16.2
Mild	12.6	9.9	10.2	8.8
Moderate	6.7	6.0	7.8	5.8
Severe	0.8	0.4	1.6	1.5
Muscle pain (other than muscle pain at the injection site)¶
Any‡	25.7	22.8	27.4	22.2
Mild	13.6	10.0	13.5	10.0
Moderate	10.5	11.9	11.9	11.5
Severe	1.6	0.8	2.0	0.8
Joint pain¶
Any‡	20.2	18.3	22.6	15.6
Mild	10.7	9.6	12.9	7.9
Moderate	8.6	8.3	8.6	6.8
Severe	1.0	0.4	1.1	0.9
Use of antipyretic medication	29.5	25.1	28.1	20.5

Serious Adverse Events

In Study 1, during the 30 days after vaccination visit 1 (at 0 months), <0.1% (1/1763) of PENBRAYA and 0% (0/649) of Trumenba + MenACWY-CRM participants reported at least 1 SAE. During the 30 days after vaccination visit 2 (at 6 months), 0.1% (2/1558) of PENBRAYA and 0% (0/562) of Trumenba participants reported at least 1 SAE. None of the SAEs were determined to be related to PENBRAYA vaccination.

In Study 2, during the 30 days after vaccination visit 1 (at 0 months), 0.4% (2/543) of PENBRAYA and 0% (0/1057) of Trumenba + MenACWY-CRM participants reported at least 1 SAE. During the 30 days after vaccination visit 2 (at 6 months), 0.2% (1/486) of PENBRAYA and 0% (0/946) of Trumenba participants reported at least 1 SAE. None of the SAEs were determined to be related to PENBRAYA vaccination.

In non-controlled Study 3, no SAEs (0/294) were reported within 30 days after either vaccination (0, 12 months).

6.2 Postmarketing Experience

The postmarketing safety experience with Trumenba and a non-U.S.-licensed Meningococcal Groups A, C, W, and Y polysaccharide tetanus toxoid (TT) conjugate vaccine (MenACWY-TT vaccine; Pfizer Inc.) is relevant to PENBRAYA since PENBRAYA includes the same group A, C, W, and Y TT-conjugated polysaccharide components and MenB recombinant protein components. Because these events are reported voluntarily from a population of uncertain size, it is not possible to reliably estimate their frequency or establish a causal relationship to vaccination. The following adverse reactions have been spontaneously reported during postmarketing use of Trumenba and MenACWY-TT and may also be seen in postmarketing experience with PENBRAYA.

Immune System Disorders: allergic reactions, including anaphylaxis

Nervous System: syncope (fainting)

8 USE IN SPECIFIC POPULATIONS

      

8.1 Pregnancy

     

Pregnancy Exposure Registry

There is a pregnancy exposure registry that monitors pregnancy outcomes in individuals exposed to PENBRAYA during pregnancy. Individuals who received PENBRAYA during pregnancy are encouraged to contact, or have their healthcare provider contact, 1-877-390-2953 to enroll in or obtain information about the registry.

Risk Summary

All pregnancies have a 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 clinical studies of PENBRAYA in pregnant individuals. Available human data on PENBRAYA administered to pregnant individuals are insufficient to inform vaccine-associated risks in pregnancy.

There were no developmental toxicity studies performed with PENBRAYA.

8.2 Lactation

Risk Summary

There are no data available to assess the effects of PENBRAYA on the breastfed infant or on milk production/excretion. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for PENBRAYA and any potential adverse effects on the breastfed child from PENBRAYA or from the underlying maternal condition. For preventive vaccines, the underlying maternal condition is susceptibility to disease prevented by the vaccine.

8.4 Pediatric Use

The safety and effectiveness of PENBRAYA have not been established in individuals <10 years of age. In a clinical study, 90% of infants younger than 12 months of age who were vaccinated with a reduced dosage formulation of Trumenba had fever. PENBRAYA contains the same MenB component, in the same quantity, as Trumenba.

8.5 Geriatric Use

The safety and effectiveness of PENBRAYA have not been established in individuals >65 years of age.

11 DESCRIPTION

PENBRAYA (Meningococcal Groups A, B, C, W, and Y Vaccine) is a suspension for intramuscular injection. PENBRAYA is supplied as a sterile Lyophilized MenACWY Component to be reconstituted with the sterile MenB Component.

The Lyophilized MenACWY Component consists of N. meningitidis serogroups A, C, W, and Y polysaccharides individually conjugated to TT. The polysaccharide for each group is grown in media containing dextrose, salt, and yeast extract, then purified by precipitation and filtration. The TT is produced by fermentation of Clostridium tetani in dextrose, salts, and tryptone N1 peptone followed by formalin detoxification, then purified by a series of physicochemical steps. The serogroups A and C polysaccharides are individually microfluidized, activated with 1-cyano-4(dimethylamino)-pyridinium tetrafluoroborate (CDAP), derivatized with adipic acid dihydrazide (ADH), and then conjugated with TT in the presence of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide) (EDAC). The serogroups W and Y polysaccharides are individually microfluidized, activated with CDAP, and then conjugated with TT. The conjugates are purified by a series of physicochemical steps then sterile filtered. Trometamol/sucrose buffer is added, and the MenACWY-TT solution is lyophilized.

The MenB Component is a sterile suspension composed of 2 recombinant lipidated factor H binding protein (fHbp) variants from N. meningitidis serogroup B, 1 from fHbp subfamily A and 1 from fHbp subfamily B (A05 and B01, respectively). The proteins are individually produced in Escherichia coli. Production strains are grown to a specific density in chemically defined fermentation growth media without antibiotics or animal-derived components. The recombinant proteins are extracted from the production strains and purified through a series of column chromatography steps. Polysorbate 80 (PS80) is added and is present in the MenB Component.

Each approximately 0.5 mL dose of PENBRAYA contains N. meningitidis serogroup A, C, W, and Y polysaccharide (5 mcg each; 20 mcg total) conjugated to tetanus toxoid (44 mcg tetanus toxoid), 2 recombinant lipidated factor H binding protein variants from N. meningitidis serogroup B (60 mcg each; total of 120 mcg protein), L-histidine (0.78 mg) , trometamol (0.097 mg), sucrose (28 mg), aluminum phosphate (0.25 mg aluminum), sodium chloride (4.65 mg), and PS80 80 (0.018 mg) at pH 6.0.

PENBRAYA does not contain any preservatives.

12 CLINICAL PHARMACOLOGY

12.1 Mechanism of Action

Protection against invasive meningococcal disease is conferred mainly by complement-mediated antibody-dependent killing of N. meningitidis.1 Vaccination with PENBRAYA induces the production of bactericidal antibodies specific to the capsular polysaccharides of N. meningitidis serogroups A, C, W, and Y and to fHbp subfamily A and B variants of N. meningitidis group B. The susceptibility of group B meningococci to bactericidal antibody is dependent upon both the antigenic similarity of the fHbp subfamily A or subfamily B vaccine antigen to the fHbp protein expressed by the bacterial strain and the amount of fHbp expressed at the bacterial surface.2

13 NONCLINICAL TOXICOLOGY

     

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

PENBRAYA has not been evaluated for the potential to cause carcinogenicity, genotoxicity, or impairment of fertility.

14 CLINICAL STUDIES

The effectiveness of PENBRAYA was assessed in Study 1 by measuring antibodies with assays that used human complement to assess serum bactericidal activity (hSBA). For serogroups A, C, W, and Y, one strain was utilized per group. For serogroup B, four meningococcal serogroup B strains expressing different fHbp variants that represent the A and B subfamilies of meningococcal serogroup B strains causing invasive disease in the U.S. and Europe were utilized. The proportions of subjects with a 4-fold or greater increase in hSBA titer for each strain, and the proportion of subjects with a titer greater than or equal to the lower limit of quantitation (LLOQ) of the assay for all four serogroup B strains (composite response) were assessed.

14.1 Immunogenicity

Study 1 was a Phase 3, randomized, active-controlled, observer-blinded, multicenter study in which participants 10 through 25 years of age in the U.S. and Europe received PENBRAYA at 0 and 6 months or Trumenba at 0 and 6 months and MenACWY-CRM at 0 months. All participants were MenB vaccine-naïve. Both MenACWY conjugate vaccine -naïve and MenACWY conjugate vaccine-exposed participants were part of the study.

Seroresponse for serogroups A, B, C, W, and Y and composite response for serogroup B following 2 doses of PENBRAYA in Study 1 are presented in Tables 3 and 4.

Among both ACWY-naïve and ACWY-exposed participants, seroresponse rates to serogroups A, C, W, and Y following 2 doses of PENBRAYA were demonstrated to be non-inferior to seroresponse rates following a single dose of MenACWY-CRM. Seroresponse and composite response rates to serogroup B primary strains among participants who received 2 doses of PENBRAYA were demonstrated to be non-inferior to seroresponse and composite response rates following 2 doses of Trumenba.

Table 3. Percentage of Subjects Achieving Seroresponses 1 Month after Receiving 2 Doses of PENBRAYA (0 and 6 Months) versus 1 Month after Single Dose of MenACWY-CRM for Serogroups A, C, W, and Y (Study 1)*,†

Abbreviations: CI = confidence interval; hSBA = serum bactericidal assay using human complement; LLOQ = lower limit of quantitation; LOD = limit of detection; MenACWY-CRM = meningococcal (serogroups A, C, W and Y) oligosaccharide diphtheria CRM197 conjugate vaccine; Trumenba= meningococcal serogroup B factor H binding protein.
Note: The LLOQ is an hSBA titer = 1:16 for A22 and 1:8 for A56, B24, and B44 and serogroups A, C, W, and Y.
Note: Seroresponse is defined as the 4-fold increase as follows: (1) For participants with a baseline hSBA titer <1:4 (LOD), a 4-fold response was defined as an hSBA titer ≥1:16. (2) For participants with a baseline hSBA titer ≥ LOD and < LLOQ, a response is defined as an hSBA titer ≥4 times the LLOQ. (3) For participants with a baseline hSBA titer ≥ LLOQ, a response is defined as an hSBA titer ≥4 times the baseline titer.
* Evaluable immunogenicity populations. † NCT04440163 ‡ Non-inferiority was demonstrated (using 10% margin) post-vaccination by assessing the difference between vaccination serogroups.
Serogroup	PENBRAYA %	Trumenba + MenACWY-CRM %	PENBRAYA – MenACWY-CRM Difference‡
	N=439-451 (Naïve) N=376-387 (Exposed)	N=244-254 (Naïve) N=222-227 (Exposed)	Difference % (95% CI)
A
ACWY-naïve	97.8	95.3	2.5 (-0.2, 6.0)
ACWY-exposed	93.8	96.9	-3.2 (-6.5, 0.5)
C
ACWY-naïve	93.3	52.4	41.0 (34.4, 47.5)
ACWY-exposed	93.8	94.7	-0.9 (-4.6, 3.3)
W
ACWY- naïve	97.3	73.0	24.3 (18.8, 30.4)
ACWY-exposed	97.1	96.4	0.7 (-2.2, 4.3)
Y
ACWY- naïve	94.4	70.6	23.8 (18.0, 30.1)
ACWY-exposed	93.0	93.7	-0.7 (-4.6, 3.8)

Table 4. Percentage of Participants Achieving Seroresponses and Composite Response 1 Month after Receiving 2 Doses of PENBRAYA (0 and 6 Months) versus 2 Doses of Trumenba (0 and 6 Months) For Serogroup B (Study 1)*,†

Abbreviations: CI = confidence interval; hSBA = serum bactericidal assay using human complement; LLOQ = lower limit of quantitation; LOD = limit of detection; MenACWY-CRM = meningococcal (serogroups A, C, W and Y) oligosaccharide diphtheria CRM197 conjugate vaccine; Trumenba= meningococcal serogroup B factor H binding protein.
Note: The LLOQ is an hSBA titer = 1:16 for A22 and 1:8 for A56, B24, and B44 and serogroups A, C, W, and Y.
Note: Seroresponse is defined as the 4-fold increase as follows: (1) For participants with a baseline hSBA titer <1:4 (LOD), a 4-fold response was defined as an hSBA titer ≥1:16. (2) For participants with a baseline hSBA titer ≥ LOD and < LLOQ, a response is defined as an hSBA titer ≥4 times the LLOQ. (3) For participants with a baseline hSBA titer ≥ LLOQ, a response is defined as an hSBA titer ≥4 times the baseline titer.
* Evaluable immunogenicity populations. † NCT04440163 ‡ Non-inferiority was demonstrated (using 10% margin) post-vaccination by assessing the difference between vaccination serogroups. § Composite response = hSBA ≥ LLOQ for all 4 primary meningococcal B strains.
	PENBRAYA %	Trumenba + MenACWY-CRM %	PENBRAYA – Trumenba Difference
Serogroup B Variant	N=755-845	N=383-419	Difference % (95% CI)
Seroresponse‡
A22	83.0	79.0	4.0 (-0.7, 8.9)
A56	95.9	94.5	1.4 (-1.0, 4.3)
B24	68.1	57.2	10.9 (5.2, 16.6)
B44	86.5	79.2	7.3 (2.9, 11.9)
Composite§
Pre-Dose 1	1.2	2.0	-
Post-Dose 2	78.3	68.7	9.6 (4.2, 15.2)

15 REFERENCES

• 1. Goldschneider I, Gotschlich EC, Artenstein MS. Human immunity to the meningococcus. I. The role of humoral antibodies. J Exp Med. (1969);129:1307–1326.
• 2. Wang X, et al. Prevalence and genetic diversity of candidate vaccine antigens among invasive Neisseria meningitidis isolates in the U.S. Vaccine 2011; 29:4739-4744.

16 HOW SUPPLIED/STORAGE AND HANDLING

16.1 How Supplied

PENBRAYA is supplied in a kit that includes a vial of Lyophilized MenACWY Component (NDC: 0069-0271-01), a prefilled syringe containing MenB Component (NDC: 0069-0332-01) and a vial adapter. The Lyophilized MenACWY Component is reconstituted with the MenB Component to form a single dose of PENBRAYA.

PENBRAYA is supplied in cartons of 1, 5, and 10 kits.

• Carton: 1 kit:

  0069-0600-01

• Carton: 5 kits:

  0069-0600-05

• Carton: 10 kits:

  0069-0600-10

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

16.2 Storage Before Reconstitution

Store refrigerated at 2°C to 8°C (36°F to 46°F) in the original carton. During storage, a white deposit and clear supernatant may be observed in the prefilled syringe containing the MenB Component. Store the carton horizontally to minimize the time necessary to resuspend the MenB Component.

Do not freeze. Discard if the carton has been frozen.

16.3 Storage After Reconstitution

After reconstitution, administer PENBRAYA immediately or store between 2°C and 30°C (36°F and 86°F) and use within 4 hours. Do not freeze.

17 PATIENT COUNSELING INFORMATION

Prior to administration of PENBRAYA:

• Inform vaccine recipient of the potential benefits and risks of vaccination with PENBRAYA.
• Advise vaccine recipient to report any adverse events to their healthcare provider or to the Vaccine Adverse Event Reporting System at 1-800-822-7967 and https://vaers.hhs.gov/.

This product’s labeling may have been updated. For the most recent prescribing information, please visit https://fda.report/dailymed/.

Manufactured by:
Pfizer Ireland Pharmaceuticals
Ringaskiddy, Cork, Ireland

US License No. 2060

LAB-1512-4.0

PRINCIPAL DISPLAY PANEL - 1 Vial/Syringe Kit Carton

NDC: 0069-0600-01
Rx only

NOTICE: Lyophilized MenACWY
Component and MenB Component
must be combined before use.

Meningococcal Groups
A, B, C, W, and Y Vaccine
PENBRAYA™

For Intramuscular Use Only
Contents: 1 kit. The kit provides a single dose of PENBRAYA™
Each kit contains:
1 vial of Lyophilized MenACWY Component
1 syringe of MenB Component
1 vial adapter

After reconstitution, a single dose of PENBRAYA is
approximately 0.5 mL.

For use in individuals 10 through 25 years of age

Pfizer

PRINCIPAL DISPLAY PANEL - 5 Vial/Syringe Kit Carton

NDC: 0069-0600-05
Rx only

NOTICE: Lyophilized MenACWY Component
and MenB Component must be combined
before use.

Meningococcal Groups
A, B, C, W, and Y Vaccine
PENBRAYA™

For Intramuscular Use Only
Contents: 5 kits. Each kit provides a
single dose of PENBRAYA™
Each kit contains:
1 vial of Lyophilized MenACWY
Component
1 syringe of MenB Component
1 vial adapter

After reconstitution, a single dose of
PENBRAYA is approximately 0.5 mL.

For use in individuals 10 through
25 years of age

Pfizer

PRINCIPAL DISPLAY PANEL - 10 Vial/Syringe Kit Carton

NDC: 0069-0600-10
Rx only

NOTICE: Lyophilized MenACWY Component and
MenB Component must be combined before use.

Meningococcal Groups
A, B, C, W, and Y Vaccine
PENBRAYA™

For Intramuscular Use Only
Contents: 10 kits. Each kit provides a single dose of
PENBRAYA™
Each kit contains:
1 vial of Lyophilized MenACWY Component
1 syringe of MenB Component
1 vial adapter

After reconstitution, a single dose of PENBRAYA is
approximately 0.5 mL.

For use in individuals 10 through 25 years of age

Pfizer

PRINCIPAL DISPLAY PANEL - 1 Vial Label

Lyophilized
MenACWY Component

NDC: 0069-0271-01

NOT TO BE USED ALONE

Reconstitute with MenB Component
to form Meningococcal Groups A, B,
C, W, and Y Vaccine (PENBRAYA™)

Single dose of approximately
0.5 mL after reconstitution

Rx only
Pfizer Ireland
US Lic. No. 2060

PRINCIPAL DISPLAY PANEL - 1 Syringe Label

NDC: 0069-0332-01
Rx only

MenB Component
Add to 1 vial of Lyophilized
MenACWY Component to form
Meningococcal
Groups A, B, C, W,
and Y Vaccine
(PENBRAYA™)

NOT TO BE USED ALONE

PAA213095

Lot:
Exp:

MenB Component

NOT TO BE USED ALONE

SHAKE WELL

Add to 1 vial of Lyophilized
MenACWY Component to form
Meningococcal
Groups A, B, C, W, and Y Vaccine
(PENBRAYA™)

Pfizer Ireland
US Lic. No. 2060

INGREDIENTS AND APPEARANCE

PENBRAYA 
meningococcal groups a, b, c, w, and y vaccine kit

Product Information
Product Type	VACCINE	Item Code (Source)	NDC: 0069-0600

Packaging
#	Item Code	Package Description	Marketing Start Date	Marketing End Date
1	NDC: 0069-0600-01	1 in 1 CARTON
1	NDC: 0069-0600-99	1 in 1 KIT; Type 9: Other Type of Part 3 Combination Product (e.g., Drug/Device/Biological Product)
2	NDC: 0069-0600-05	5 in 1 CARTON
2	NDC: 0069-0600-99	1 in 1 KIT; Type 9: Other Type of Part 3 Combination Product (e.g., Drug/Device/Biological Product)
3	NDC: 0069-0600-10	10 in 1 CARTON
3	NDC: 0069-0600-99	1 in 1 KIT; Type 9: Other Type of Part 3 Combination Product (e.g., Drug/Device/Biological Product)

Quantity of Parts
Part #	Package Quantity	Total Product Quantity
Part 1	1 VIAL, GLASS	0.5 mL
Part 2	1 SYRINGE	0.5 mL

Part 1 of 2

LYOPHILIZED MENACWY COMPONENT 
lyophilized menacwy component injection, powder, lyophilized, for suspension

Product Information
Item Code (Source)	NDC: 0069-0271
Route of Administration	INTRAMUSCULAR

Active Ingredient/Active Moiety
Ingredient Name	Basis of Strength	Strength
NEISSERIA MENINGITIDIS GROUP A CAPSULAR POLYSACCHARIDE TETANUS TOXOID CONJUGATE ANTIGEN (UNII: T4GYX3110D) (NEISSERIA MENINGITIDIS GROUP A CAPSULAR POLYSACCHARIDE TETANUS TOXOID CONJUGATE ANTIGEN - UNII:T4GYX3110D)	NEISSERIA MENINGITIDIS GROUP A CAPSULAR POLYSACCHARIDE TETANUS TOXOID CONJUGATE ANTIGEN	5 ug  in 0.5 mL
NEISSERIA MENINGITIDIS GROUP C CAPSULAR POLYSACCHARIDE TETANUS TOXOID CONJUGATE ANTIGEN (UNII: ZT89E5A103) (NEISSERIA MENINGITIDIS GROUP C CAPSULAR POLYSACCHARIDE TETANUS TOXOID CONJUGATE ANTIGEN - UNII:ZT89E5A103)	NEISSERIA MENINGITIDIS GROUP C CAPSULAR POLYSACCHARIDE TETANUS TOXOID CONJUGATE ANTIGEN	5 ug  in 0.5 mL
NEISSERIA MENINGITIDIS GROUP W-135 CAPSULAR POLYSACCHARIDE TETANUS TOXOID CONJUGATE ANTIGEN (UNII: L77OK410KW) (NEISSERIA MENINGITIDIS GROUP W-135 CAPSULAR POLYSACCHARIDE TETANUS TOXOID CONJUGATE ANTIGEN - UNII:L77OK410KW)	NEISSERIA MENINGITIDIS GROUP W-135 CAPSULAR POLYSACCHARIDE TETANUS TOXOID CONJUGATE ANTIGEN	5 ug  in 0.5 mL
NEISSERIA MENINGITIDIS GROUP Y CAPSULAR POLYSACCHARIDE TETANUS TOXOID CONJUGATE ANTIGEN (UNII: 4WAN8PQK15) (NEISSERIA MENINGITIDIS GROUP Y CAPSULAR POLYSACCHARIDE TETANUS TOXOID CONJUGATE ANTIGEN - UNII:4WAN8PQK15)	NEISSERIA MENINGITIDIS GROUP Y CAPSULAR POLYSACCHARIDE TETANUS TOXOID CONJUGATE ANTIGEN	5 ug  in 0.5 mL

Inactive Ingredients
Ingredient Name	Strength
CLOSTRIDIUM TETANI TOXOID ANTIGEN (FORMALDEHYDE INACTIVATED) (UNII: K3W1N8YP13)	44 ug  in 0.5 mL
TROMETHAMINE (UNII: 023C2WHX2V)	97 ug  in 0.5 mL
SUCROSE (UNII: C151H8M554)	28 mg  in 0.5 mL

Packaging
#	Item Code	Package Description	Marketing Start Date	Marketing End Date
1	NDC: 0069-0271-01	0.5 mL in 1 VIAL, GLASS; Type 0: Not a Combination Product

Marketing Information
Marketing Category	Application Number or Monograph Citation	Marketing Start Date	Marketing End Date
BLA	BLA125770	11/27/2023

Part 2 of 2

MENB COMPONENT 
menb component suspension

Product Information
Item Code (Source)	NDC: 0069-0332
Route of Administration	INTRAMUSCULAR

Active Ingredient/Active Moiety
Ingredient Name	Basis of Strength	Strength
NEISSERIA MENINGITIDIS GROUP B RECOMBINANT LP2086 A05 PROTEIN VARIANT ANTIGEN (UNII: 583WCD0IZI) (NEISSERIA MENINGITIDIS GROUP B RECOMBINANT LP2086 A05 PROTEIN VARIANT ANTIGEN - UNII:583WCD0IZI)	NEISSERIA MENINGITIDIS GROUP B RECOMBINANT LP2086 A05 PROTEIN VARIANT ANTIGEN	0.06 mg  in 0.5 mL
NEISSERIA MENINGITIDIS GROUP B RECOMBINANT LP2086 B01 PROTEIN VARIANT ANTIGEN (UNII: 7MBD4K530D) (NEISSERIA MENINGITIDIS GROUP B RECOMBINANT LP2086 B01 PROTEIN VARIANT ANTIGEN - UNII:7MBD4K530D)	NEISSERIA MENINGITIDIS GROUP B RECOMBINANT LP2086 B01 PROTEIN VARIANT ANTIGEN	0.06 mg  in 0.5 mL

Inactive Ingredients
Ingredient Name	Strength
SODIUM CHLORIDE (UNII: 451W47IQ8X)	4.38 mg  in 0.5 mL
HISTIDINE (UNII: 4QD397987E)	0.78 mg  in 0.5 mL
POLYSORBATE 80 (UNII: 6OZP39ZG8H)	0.018 mg  in 0.5 mL
ALUMINUM PHOSPHATE (UNII: F92V3S521O)	0.25 mg  in 0.5 mL
WATER (UNII: 059QF0KO0R)	498 mg  in 0.5 mL

Packaging
#	Item Code	Package Description	Marketing Start Date	Marketing End Date
1	NDC: 0069-0332-01	0.5 mL in 1 SYRINGE; Type 9: Other Type of Part 3 Combination Product (e.g., Drug/Device/Biological Product)

Marketing Information
Marketing Category	Application Number or Monograph Citation	Marketing Start Date	Marketing End Date
BLA	BLA125770	11/27/2023

Marketing Information
Marketing Category	Application Number or Monograph Citation	Marketing Start Date	Marketing End Date
BLA	BLA125770	11/27/2023

Labeler - Pfizer Laboratories Div Pfizer Inc (134489525)

Establishment
Name	Address	ID/FEI	Business Operations
Pfizer Health AB		354433591	ANALYSIS(0069-0600) , API MANUFACTURE(0069-0600)

Establishment
Name	Address	ID/FEI	Business Operations
Pfizer Inc		004954111	API MANUFACTURE(0069-0600) , ANALYSIS(0069-0600)

Establishment
Name	Address	ID/FEI	Business Operations
Wyeth Pharmaceutical Division of Wyeth Holdings LLC		883534067	ANALYSIS(0069-0600) , API MANUFACTURE(0069-0600)

Establishment
Name	Address	ID/FEI	Business Operations
Pfizer Ireland Pharmaceuticals		985586408	ANALYSIS(0069-0600) , API MANUFACTURE(0069-0600) , MANUFACTURE(0069-0600)

Establishment
Name	Address	ID/FEI	Business Operations
Pfizer Manufacturing Austria GmbH		300453240	ANALYSIS(0069-0600)

Establishment
Name	Address	ID/FEI	Business Operations
Pfizer Manufacturing Belgium NV		370156507	ANALYSIS(0069-0600) , MANUFACTURE(0069-0600) , PACK(0069-0600) , LABEL(0069-0600)