PENBRAYA™

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.

	Step 1. Attachment of the vial adapter to the vial. • Remove the flip top cap from the vial of Lyophilized MenACWY Component. • Peel off the top cover from the vial adapter packaging. • While keeping the vial adapter in its packaging, center the adapter over the vial’s stopper and attach to the vial with a straight downward push. • Remove the packaging.
	Step 2. Resuspension of the MenB Component. • Shake the syringe containing the MenB Component vigorously to obtain a white homogenous suspension. Do not use if the contents cannot be resuspended.
	Step 3. Connection of the syringe containing the MenB Component to the vial adapter. • Hold the syringe by the Luer lock adapter. • Twist to remove the syringe cap. • Connect the syringe to the vial adapter by turning the Luer lock.
	Step 4. Reconstitution of the Lyophilized MenACWY Component with the MenB Component to form PENBRAYA. • Inject the entire contents of the syringe into the vial. • Hold the plunger rod down and gently swirl the vial until the powder is completely dissolved (less than 1 minute).
	Step 5. Withdrawal of PENBRAYA. • Invert the vial completely and slowly withdraw the entire contents into the syringe for an approximately 0.5 mL dose of PENBRAYA. • Twist to disconnect the syringe from the vial adapter. • Attach a sterile needle suitable for intramuscular injection.

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.

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.

6.1 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.

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)

8.1 Pregnancy

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.

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

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

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

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.

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.

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.