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PENBRAYA- meningococcal groups a, b, c, w, and y vaccine 
Pfizer Laboratories Div Pfizer Inc


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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.

PENBRAYATM (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: 9/2024


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.


FULL PRESCRIBING INFORMATION




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.

Vial of Lyophilized MenACWY Component

Syringe of MenB Component

Vial Adapter

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

Step 1. Preparation of vial and vial adapter

•Remove plastic flip-off cap from vial containing the Lyophilized MenACWY
Component. •Cleanse the rubber stopper.•Without removing the vial adapter from
its packaging, peel off the top cover.

Step 2. Attachment of vial adapter

•Hold the base of the vial on a flat surface.•Keep the vial adapter in the
packaging and orient it vertically over the center of the vial so that the
adapter spike aligns with the center of the vial’s rubber stopper. •Connect the
vial adapter to the vial with a straight downward push. The vial adapter will
lock into place.•Do not push vial adapter in at an angle as this may result in
leaking during use.•Remove the vial adapter packaging.

Step 3. Resuspension of the MenB Component

•Shake the syringe vigorously to obtain a white homogenous suspension. Do not
use if the contents cannot be resuspended.

Step 4. Removal of syringe cap

•For all syringe assembly steps, hold the syringe only by the Luer lock adapter
located at the tip of the syringe. This will prevent the Luer lock adapter from
detaching during use.•Remove the syringe cap by slowly turning the cap
counter-clockwise while holding the Luer lock adapter.

Step 5. Connection of syringe to vial adapter

•Hold the syringe’s Luer lock adapter and connect it to the vial adapter by
turning clockwise.•Stop turning when you feel resistance, overtightening the
syringe may result in leaking during use.•Once the syringe is securely attached
to the vial adapter, there will be a small space between the top of the vial
adapter and the Luer lock adapter of the syringe.

Step 6. Reconstitution of Lyophilized MenACWY Component with MenB Component to
form PENBRAYA

•Inject the entire contents of the syringe containing the MenB Component into
the vial.•Do not remove the empty syringe.•While holding the plunger rod down,
gently swirl the vial in a circular motion until the powder is completely
dissolved (less than 1 minute).

Step 7. Withdrawal of PENBRAYA

•Invert the vial completely with the vial adapter and syringe still
attached.•Slowly withdraw the entire contents into the syringe to ensure an
approximately 0.5 mL dose of PENBRAYA for administration.•Do not pull the
plunger rod out.

Step 8. Disconnection of syringe

•Hold the Luer lock adapter of the syringe and disconnect the syringe from the
vial adapter by turning counter-clockwise.

Step 9. Attachment of needle

•Attach a sterile needle suitable for intramuscular injection to the syringe
containing PENBRAYA.

Step 10. Visual inspection

•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.


2.3 ADMINISTRATION

For intramuscular use only.

After reconstitution, 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 1Abbreviations: 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 tetrafluorobate (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://dailymed.nlm.nih.gov/dailymed/.

Manufactured by:
Pfizer Ireland Pharmaceuticals
Ringaskiddy, Cork, Ireland

US License No. 2060



LAB-1512-3.0



Revised: 9/2024
Document Id: 8a29ce98-e759-428a-b7ac-be1099df56f1
53404-0
Set id: fd5652b6-5ae4-437e-a456-47deaf500794
Version: 4
Effective Time: 20240918
 
Pfizer Laboratories Div Pfizer Inc