Pharmaceutical Name

Trade (marketing or proprietary) name: BEXSERO, TRUMENBA®

Generic (nonproprietary or active ingredient) name: Meningococcal Group B Vaccine suspension for intramuscular injection

Indication and Usage

Reason the product has been approved for sale on the market.

BEXSERO is a vaccine indicated for active immunization to prevent invasive disease caused by Neisseria meningitidis serogroup B. BEXSERO is approved for use in individuals aged 10 through 25 years. Approval of BEXSERO is based on demonstration of immune response, as measured by serum bactericidal activity against three serogroup B strains representative of prevalent strains in the United States. The effectiveness of BEXSERO against diverse serogroup B strains has not been confirmed.

Trumenba is indicated for active immunization to prevent invasive disease caused by Neisseria meningitidis serogroup B. Trumenba is approved for use in individuals 10 through 25 years of age

Manufacturer Insert

Ingredients

Also known as “excipients” for vaccines.

Each 0.5-mL dose of BEXSERO is formulated to contain 50 micrograms each of recombinant proteins Neisserial adhesin A (NadA), Neisserial Heparin Binding Antigen (NHBA), and factor H binding protein (fHbp), 25 micrograms of Outer Membrane Vesicles (OMV), 1.5 mg aluminum hydroxide (0.519 mg of Al3+), 3.125 mg sodium chloride, 0.776 mg histidine, and 10 mg sucrose at pH 6.4 to 6.7. Each dose contains less than 0.01 micrograms kanamycin (by calculation).

Trumenba is a sterile suspension composed of two recombinant lipidated factor H binding protein (fHbp) variants from N. meningitidis serogroup B, one from fHbp subfamily A and one from subfamily B (A05 and B01, respectively). The proteins are individually produced in E. coli. Production strains are grown in defined fermentation growth media to a specific density. The recombinant proteins are extracted from the production strains and purified through a series of column chromatography steps. Polysorbate 80 (PS80) is added to the drug substances and is present in the final drug product.

Each 0.5 mL dose contains 60 micrograms of each fHbp variant (total of 120 micrograms of protein), 0.018 mg of PS80 and 0.25 mg of Al³+ as AlPO4 in 10 mM histidine buffered saline at pH 6.0.

Contraindications

Per the FDA, contraindications are conditions in a recipient that increases the risk for a serious adverse reaction. Product should not be administered when a patient has a listed contraindication.

BEXSERO

Do not administer BEXSERO to individuals with a history of a severe allergic reaction (e.g., anaphylaxis) to any component of BEXSERO or after a previous dose of BEXSERO.

TRUMENBA®

Severe allergic reaction (e.g. anaphylaxis) to any component of Trumenba.

Warnings and Precautions

Per the FDA, warnings are clinically significant adverse reactions or risks. According to the CDC, a precaution is a condition in a recipient that might increase the risk for a serious adverse reaction, might cause diagnostic confusion, or might compromise the effectiveness of the product. In general, a product should be deferred when a precaution is present.

BEXSERO

Management of Allergic Reactions: Appropriate medical treatment must be immediately available to manage potential anaphylactic reactions following administration of BEXSERO.

Syncope: Syncope (fainting) can occur in association with administration of BEXSERO. Ensure procedures are in place to avoid injury from falling associated with syncope.

Limitation of Vaccine Effectiveness: BEXSERO may not protect all vaccine recipients. BEXSERO may not provide protection against all meningococcal serogroup B strains.

Altered Immunocompetence: Some individuals with altered immunocompetence may have reduced immune responses to BEXSERO.

Complement Deficiency: Persons with certain complement deficiencies and persons receiving treatment that inhibits terminal complement activation (for example, eculizumab) are at increased risk for invasive disease caused by N. meningitidis serogroup B even if they develop antibodies following vaccination with BEXSERO.

TRUMENBA®

Management of Allergic Reactions: Epinephrine and other appropriate agents used to manage immediate allergic reactions must be immediately available should an acute anaphylactic reaction occur following administration of Trumenba.

Altered Immunocompetence:

• Reduced Immune Response – Some individuals with altered immunocompetence may have reduced immune responses to Trumenba.
• Complement Deficiency – Persons with certain complement deficiencies and persons receiving treatment that inhibits terminal complement activation (for example, eculizumab) are at increased risk for invasive disease caused by N. meningitidis serogroup B even if they develop antibodies following vaccination with Trumenba.

Limitation of Vaccine Effectiveness: Vaccination with Trumenba may not protect all vaccine recipients against N. meningitidis serogroup B infections.

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

Manufacturer-Listed Adverse Reactions

Per the CDC, adverse reactions are an undesirable medical condition that has been demonstrated to be caused by a vaccine. Evidence for the causal relation is usually obtained through randomized clinical trials, controlled epidemiologic studies, isolation of the vaccine strain from the pathogenic site, or recurrence of the condition with repeated vaccination (i.e., rechallenge); synonyms include side effect and adverse effect.

Bexsero® can cause: Injection site reactions (including extensive swelling of the vaccinated limb, blisters at or around the injection site, and the injection site nodule which may persist for more than 1 month), Allergic/anaphylactic reactions, Rash, Eye Swelling, Syncope (fainting), Vasovagal responses.

Trumenba® can cause: Hypersensitivity reactions, Anaphylactic reactions, Syncope (fainting).

Limitations of Effectiveness

BEXSERO may not protect all vaccine recipients. BEXSERO may not provide protection against all meningococcal serogroup B strains

Vaccination with Trumenba may not protect all vaccine recipients against N. meningitidis serogroup B infections.

Specific Populations

Pregnancy

There are no adequate and well-controlled studies of BEXSERO in pregnant women in the U.S. Available human data on BEXSERO administered to pregnant women are insufficient to inform vaccine-associated risks in pregnancy.

There are no adequate and well-controlled studies of Trumenba in pregnant women. Available human data on Trumenba administered to pregnant women are insufficient to inform vaccine-associated risks in pregnancy.

Breastfeeding

It is not known whether the vaccine components of BEXSERO are excreted in human milk.

Available data are not sufficient to assess the effects of Trumenba on the breastfed infant or on milk production/excretion.

Fertility

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

Trumenba has not been evaluated for carcinogenic or mutagenic potential or impairment of fertility in males. Vaccination of female rabbits with Trumenba had no effect on fertility

Pediatric

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

Safety and effectiveness have not been established in children <10 years of age. In a clinical study, 90% of infants <12 months of age who were vaccinated with a reduced dosage formulation had fever. Clinical data strongly suggest that a two-dose regimen of Trumenba would be ineffective in children 1 to <10 years of age.

Mechanism of Action

This is the specific biochemical interaction through which a drug or vaccine substance produces its pharmacological effect. This section also includes the minimum protective level designated for a certain disease.

BEXSERO

Protection against invasive meningococcal disease is conferred mainly by complement-mediated antibody-dependent killing of N. meningitidis. NHBA, NadA, and fHbp are proteins found on the surface of meningococci and contribute to the ability of the bacteria to cause disease. OMV derived from the bacterial outer membrane contains PorA and other surface proteins. Vaccination with BEXSERO leads to the production of antibodies directed against NHBA, NadA, fHbp, and OMV. The susceptibility of serogroup B meningococci to complement-mediated antibody-dependent killing following vaccination with BEXSERO 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.

TRUMENBA®

Protection against invasive meningococcal disease is conferred mainly by complement-mediated antibody-dependent killing of N. meningitidis. The effectiveness of Trumenba was assessed by measuring serum bactericidal activity using human complement (hSBA).
fHbp is one of many proteins found on the surface of meningococci and contributes to the ability of the bacterium to avoid host defenses. fHbps can be categorized into two immunologically distinct subfamilies, A and B.1 The susceptibility of serogroup B meningococci to complement-mediated antibody-dependent killing following vaccination with Trumenba is dependent on both the antigenic similarity of the bacterial and vaccine
fHbps, as well as the amount of fHbp expressed on the surface of the invading meningococci.

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