Penmenvy: Package Insert / Prescribing Info

2.1 Dose and Schedule

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

2.2 Preparation

PENMENVY is supplied as one vial of Lyophilized MenACWY Component (powder) and one prefilled syringe of MenB Component (liquid) which must be combined before administration.

Use only the supplied MenB Component to reconstitute the Lyophilized MenACWY Component.

2.3 Administration

Administer intramuscularly.

Administer PENMENVY immediately after reconstitution.

5.1 Management of Allergic Reactions

Appropriate medical treatment must be immediately available to manage potential anaphylactic reactions following administration of PENMENVY.

5.2 Syncope

Syncope (fainting) has occurred in association with administration of PENMENVY. Procedures should be in place to avoid injury from fainting.

5.3 Limitation of Vaccine Effectiveness

Vaccination with PENMENVY may not protect all vaccine recipients. PENMENVY may not provide protection against all meningococcal serogroup B strains [see Clinical Pharmacology (12.1)].

5.4 Altered Immunocompetence

Reduced Immune Response

Immunocompromised persons, including those receiving immunosuppressive therapy, may have reduced immune responses to PENMENVY.

Complement Deficiency

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

5.5 Guillain-Barré Syndrome

Guillain‑Barré syndrome (GBS) has been reported in temporal relationship following administration of a U.S.‑licensed meningococcal quadrivalent polysaccharide conjugate vaccine. The decision by the healthcare professional to administer PENMENVY 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 with rates in the clinical trials of another vaccine and may not reflect the rates observed in practice.

The safety of PENMENVY was evaluated in 12 clinical studies1 in which a total of 3,718 participants received at least one dose of PENMENVY. Participants in Study 1 (aged 10 through 25 years) and Study 2 (aged 15 through 25 years) were scheduled to receive PENMENVY according to the approved dosing schedule (2 doses administered 6 months apart). Participants in the other studies may have received PENMENVY according to unapproved dosing schedules. Across the 12 studies, 2,969 participants received at least 1 dose of BEXSERO (Meningococcal Group B Vaccine) and 361 participants received a single dose of MENVEO [Meningococcal (Groups A, C, Y, and W‑135) Oligosaccharide Diphtheria CRM197 Conjugate Vaccine]. Across the studies, the median age was 16 years, males comprised 46%, and 86% of participants were White, 6% were Black, 4% were Asian, and 4% were of other racial groups. In these studies, 13% of participants were Hispanic. Approximately 35% of participants were from the U.S.

Nine of the 12 studies (including Study 1 and Study 2) collected non‑serious unsolicited adverse events through 30 days after each vaccination, and the other 3 studies collected these events through 7 days after each vaccination. All studies collected serious adverse events through at least 1 month following the last vaccination. Study 1 and Study 2 collected serious adverse events through 12 months following the first vaccination and at least 5 months following the last vaccination.

Study 1 (NCT04502693) was a randomized, controlled, observer‑blind study conducted in 7 countries (U.S., Australia, Canada, Czech Republic, Estonia, Finland, and Turkey). In this study, 1,657 participants aged 10 through 25 years received at least 1 dose of PENMENVY. Participants were scheduled to receive 2 doses of PENMENVY 6 months apart. Separate groups received BEXSERO either as a 0‑, 2‑, 6‑month schedule or 0‑, 6‑month schedule. A single dose of MENVEO was administered 1 month after the third dose in the 0‑, 2‑, 6‑month group and 2 months after the first dose of BEXSERO in the 0‑, 6‑month group (these participants received saline placebo at month 7). A separate group received a single dose of MENVEO at month 0, a saline placebo dose at month 2, and doses of BEXSERO at months 6 and 7 (an unapproved BEXSERO dosing regimen). All participants were MenB vaccine‑naïve. Both MenACWY conjugate vaccine‑naïve (87%) and MenACWY conjugate vaccine‑experienced (13%, vaccinated at least 4 years prior to study enrollment) participants were part of the study. The median age was 16 years, males comprised 47%, and 89% of participants were White, 5% were Asian, 4% were Black, and 2% were of other racial groups. Among study participants, 5% were Hispanic. Approximately 30% of participants were from the U.S.

Study 2 (NCT04707391) was a randomized, controlled, observer‑blind study conducted in 4 countries (U.S., Australia, Canada, and Argentina). In this study, 626 participants aged 15 through 25 years received at least 1 dose of PENMENVY. All participants were MenACWY conjugate vaccine‑experienced (vaccinated at least 4 years prior to study enrollment). A separate group received a single dose of MENVEO followed 6 months later by 2 doses of BEXSERO administered 1 month apart (an unapproved BEXSERO dosing regimen). In this study, the median age was 16 years, males comprised 47%, and 75% of participants were White, 14% were Black, 6% were of other racial groups, and 4% were Asian. Among study participants, 30% were Hispanic. Approximately 59% of participants were from the U.S.

Solicited Adverse Reactions

In Study 1, solicited local and systemic adverse reactions were collected for 7 days after study vaccination using electronic diaries. The rates of local and systemic adverse reactions reported in Study 1 among participants aged 10 through 25 years following each dose of PENMENVY administered 6 months apart, each dose of BEXSERO administered 6 months apart, or a single dose of MENVEO are presented in Table 1.

In Study 2, solicited local and systemic adverse reactions were collected for 7 days after study vaccination using electronic diaries. The rates of local and systemic adverse reactions reported in Study 2 among participants aged 15 through 25 years following each dose of PENMENVY administered 6 months apart or a single dose of MENVEO are presented in Table 2.

Unsolicited Adverse Events

In an analysis across the 12 studies, unsolicited adverse events that were reported in participants who received PENMENVY (N = 3,718) and were determined to be causally related included syncope, dizziness, and pre‑syncope (0.9%); lymphadenopathy (0.2%); and hypersensitivity (0.1%). The onset of syncope, dizziness, pre‑syncope, and lymphadenopathy ranged from 1 to 30 days and the onset of hypersensitivity ranged from 9 to 27 days.

Serious Adverse Events

In Study 1, serious adverse events that occurred through 12 months following the first vaccination and at least 5 months following the last vaccination were reported by 1.5% of participants in the PENMENVY group (N = 1,648), 2.4% of participants in the group who received BEXSERO as a 0‑, 6‑month schedule with a dose of MENVEO at month 2 (N = 900), and 2.8% of participants in the group who received MENVEO at month 0 and BEXSERO at months 6 and 7 (N = 178).

In Study 2, serious adverse events that occurred through 12 months following the first vaccination and at least 5 months following the last vaccination were reported by 2.9% of participants in the PENMENVY group (N = 626) and 1.1% of participants in the group who received MENVEO at month 0 and BEXSERO at months 6 and 7 (N = 621).

Across the 12 clinical studies, serious adverse events were reported within 30 days after any dose by 0.6% of participants who received PENMENVY (N = 3,718), 0.4% of participants who received BEXSERO (N = 2,969), and 0.3% of participants who received MENVEO (N = 361). Two serious adverse events reported following administration of PENMENVY were assessed as vaccine‑related and are described below.

In Study 3,1 connective tissue disorder was reported in an adolescent participant who developed 3 episodes of petechiae (7 days after PENMENVY Dose 1, 18 days after PENMENVY Dose 2 [given 1 month after Dose 1], and 17 days after HAVRIX [Hepatitis A Vaccine]) and was diagnosed with a connective tissue disorder 44 days after PENMENVY Dose 2.

In Study 3,1 seizures were reported in an adult participant with onset 9 hours after PENMENVY Dose 1.

6.2 Postmarketing Experience

The following adverse reactions have been reported during postapproval use of BEXSERO or MENVEO. The postmarketing safety experience with BEXSERO and MENVEO is relevant because PENMENVY contains the same group A, C, W, and Y CRM197‑conjugated oligosaccharide components and MenB recombinant protein components. Because these reactions were reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to the vaccine exposure.

Blood and Lymphatic System Disorders

Lymphadenopathy.a,b

Ear and Labyrinth Disorders

Hearing impaired,b ear pain,b vertigo,b vestibular disorder.b

Eye Disorders

Eyelid ptosis.b

General Disorders and Administration Site Conditions

Injection site reactions (including injection site pruritus,b pain,b erythema,b inflammation,b swelling,b extensive swelling of the vaccinated limb,a,b blisters at or around the injection site,a and injection site nodule which may persist for more than 1 montha), fatigue,b malaise,b pyrexia.b

Immune System Disorders

Allergic reactions,a anaphylactic reactions,a eye swelling,a rash,a hypersensitivity reactions,b anaphylaxis.b

Infections and Infestations

Vaccination site cellulitis.b

Injury, Poisoning, and Procedural Complications

Fall,b head injury.b

Investigation

Alanine aminotransferase increased,b body temperature increased.b

Musculoskeletal and Connective Tissue Disorders

Arthralgia,b bone pain.b

Nervous System Disorders

Dizziness,b syncope,a,b tonic convulsion,b headache,b facial paresis,b balance disorder,b vasovagal responses to injection.a

Respiratory, Thoracic, and Mediastinal Disorders

Oropharyngeal pain.b

Skin and Subcutaneous Tissue Disorders

Skin exfoliation.b

a Observed with BEXSERO.

b Observed with MENVEO.

Postmarketing Observational Safety Study

In a postmarketing observational safety study conducted in a U.S. health maintenance organization, data from electronic health records of 48,899 persons aged 11 through 21 years were used to evaluate pre‑specified events of interest following vaccination with MENVEO. Using a self‑controlled case series method, Bell’s palsy showed a statistically significant increased risk in the period 1 to 84 days post vaccination compared with the control period, with an overall adjusted relative incidence of 2.9 (95% CI: 1.1‑7.5). Among the 8 reported cases of Bell’s palsy, 6 cases occurred in persons who received MENVEO concomitantly with one or more of the following vaccines: Tetanus Toxoid, Reduced Diphtheria Toxoid and Acellular Pertussis Vaccine Adsorbed (Tdap), a human papillomavirus vaccine, and Influenza Vaccine. All reported Bell’s palsy cases resolved.

8.1 Pregnancy

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 adequate and well-controlled studies of PENMENVY in pregnant women. Available human data on PENMENVY administered to pregnant women are insufficient to inform vaccine-associated risks in pregnancy.

A developmental toxicity study was performed in female rabbits administered a dose of PENMENVY (0.5 mL) on 5 occasions, three times prior to mating and twice during gestation. This study revealed no vaccine‑related effects on female fertility, fetal development or postnatal development (see Data).

Data

Animal Data: In a developmental toxicity study, female rabbits were administered a dose of PENMENVY (0.5 mL) by intramuscular injection on 5 occasions: 35, 21 and 7 days prior to mating, and on gestation days 7 and 20. No vaccine‑related adverse effects on female fertility, fetal development, or postnatal development were reported in the study.

8.2 Lactation

Risk Summary

It is not known whether the vaccine components of PENMENVY are excreted in human milk. Available data are not sufficient to assess the effects of PENMENVY 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 PENMENVY and any potential adverse effects on the breastfed child from PENMENVY 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

Safety and effectiveness of PENMENVY have not been established in children younger than 10 years of age.

8.5 Geriatric Use

Safety and effectiveness of PENMENVY in adults aged 65 years and older have not been established.

12.1 Mechanism of Action

Protection against invasive meningococcal disease is conferred mainly by complement‑mediated antibody‑dependent killing of N. meningitidis strains.4 Immunization with PENMENVY is intended to stimulate the production of antibodies with bactericidal activity specific to the capsular polysaccharides of N. meningitidis serogroups A, C, W, and Y and to the protein antigens NHBA, NadA, fHbp and OMV expressed by serogroup B meningococcal strains.

NHBA, NadA, and fHbp are proteins found on the surface of meningococci and contribute to the ability of the bacterium to cause disease. OMV derived from the bacterial outer membrane contains PorA and other surface proteins. The susceptibility of serogroup B meningococci to complement‑mediated antibody‑dependent killing following vaccination with PENMENVY is dependent on both the antigenic similarity of the bacterial and vaccine antigens, as well as the amount of antigen expressed on the surface of the invading meningococci.

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

PENMENVY has not been evaluated for carcinogenic or mutagenic potential or impairment of male fertility in animals.

16.1 How Supplied

PENMENVY is supplied in cartons containing:

•

10 vials of Lyophilized MenACWY Component (powder) and

•

10 prefilled TIP‑LOK syringes (Luer Lock syringes) of MenB Component (liquid) packaged without needles.

TIP‑LOK syringes are to be used with Luer Lock compatible needles.

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

16.2 Storage Before Reconstitution

Store refrigerated, away from the freezer compartment, at 36°F to 46°F (2°C to 8°C).

Store in the original carton to protect from light.

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

16.3 Storage After Reconstitution

Use immediately after reconstitution.