The most commonly reported (≥10%) solicited adverse reactions after Dose 1 and Dose 2, respectively, in Study 1 in participants aged 10 through 25 years (87% of whom were MenACWY conjugate ...
The most commonly reported (≥10%) solicited adverse reactions after Dose 1 and Dose 2, respectively, in Study 1 in participants aged 10 through 25 years (87% of whom were MenACWY conjugate vaccine‑naïve) were pain at the injection site (92% and 88%), fatigue (51% and 42%), headache (42% and 36%), myalgia (15% and 12%), nausea (15% and 10%), erythema (13% and 12%), and swelling (13% and 12%).
The most commonly reported (≥10%) solicited adverse reactions after Dose 1 and Dose 2, respectively, in Study 2 in MenACWY conjugate vaccine‑experienced participants aged 15 through 25 years were pain at the injection site (80% and 74%), headache (41% and 33%), fatigue (40% and 33%), myalgia (15% and 13%), and nausea (15% and 12%).
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.
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