Bexsero

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 10 through 25 years of age.

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.

Mechanism Of Action

Protection against invasive meningococcal disease is conferred mainly by complement-mediated antibody-dependent killing of N. meningitidis. The effectiveness of BEXSERO was assessed by measuring serum bactericidal activity using human complement (hSBA).

NHBA, NadA, fHbp, and PorA are proteins found on the surface of meningococci and contribute to the ability of the bacterium to cause disease. Vaccination with BEXSERO leads to the production of antibodies directed against NHBA, NadA, fHbp, and PorA P1.4 (present in 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.

Clinical Studies

The immunogenicity of BEXSERO following 2 doses was evaluated in individuals 11 through 24 years of age. Serum bactericidal antibodies were measured with hSBA assays using three strains selected to measure responses to one of three vaccine antigens, either fHbp, NadA or PorA P1.4, prevalent among strains in the US. A suitable strain for assessing bactericidal activity of NHBA-specific antibodies was not available. Studies assessed the proportion of subjects who achieved a 4-fold or greater increase in hSBA titer for each of the three strains, and the proportion of subjects with a titer greater than or equal to the lower limit of quantitation (LLOQ) of the assay for all three strains (composite response). The LLOQ was defined as the lowest amount of the antibody in a sample that can be reliably quantified. Available data showed that baseline antibody titers across populations vary.

Immunogenicity

In a clinical trial conducted in Canada and Australia, adolescents 11 through 17 years of age received two doses of BEXSERO one month apart. The hSBA responses one month after the second dose are shown in Table 2.

Table 2: Bactericidal Antibody Response Rates Following 2 Doses of BEXSERO Administered 1 Month Apart to Canadian and Australian Adolescentsa

In a randomized, controlled clinical trial conducted in the UK among university students 18 through 24 years of age, hSBA responses in a subset of participants who received BEXSERO were measured 1 month and 11 months after the second dose (Table 3).

Table 3: Bactericidal Antibody Response Rates Following 2 Doses of BEXSERO Administered 1 Month Apart to University Students in the UKa

Serious side effects have been reported with Bexsero. See the “Bexsero Precautions” section.

Common side effects of Bexsero include the following:

• pain and swelling at the injection site
• headache
• diarrhea
• muscle/joint pain
• fatigue
• chills

This is not a complete list of Bexsero side effects. Ask your doctor or pharmacist for more information.

Tell your doctor if you have any side effect that bothers you or that does not go away.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

Mechanism of Action

Protection against invasive meningococcal disease is conferred mainly by complement-mediated antibody-dependent killing of N meningitidis

You should not receive this vaccine if you have ever had an allergic reaction to meningococcal group B vaccine.

Get emergency medical help if you have signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Keep track of any and all side effects you have after receiving this vaccine. When you receive a booster dose, you will need to tell the doctor if the previous shot caused any side effects.

You should not receive a booster vaccine if you had a life-threatening allergic reaction after the first shot.

Becoming infected with meningococcal disease and developing meningitis (infection of the spinal cord and lining of the brain) is much more dangerous to your health than receiving this vaccine. However, like any medicine, this vaccine can cause side effects but the risk of serious side effects is extremely low.

You may feel faint after receiving this vaccine. Some people have had seizure-like reactions after receiving this vaccine. Your doctor may want you to remain under observation during the first 15 minutes after the injection.

Common side effects may include:

• headache;

• feeling tired;

• muscle or joint pain;

• chills;

• nausea; or

• pain, redness, or a hard lump where the shot was given.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report vaccine side effects to the US Department of Health and Human Services at 1 800 822 7967.

This section provides information on the proper use of a number of products that contain meningococcal vaccine. It may not be specific to Bexsero. Please read with care.

A nurse or other trained health professional will give this vaccine to you or your child.

• Menomune® vaccine:
  • For prevention of meningococcal meningitis:
    • Adults and children—One dose injected under the skin.
    • Usually a person needs to receive the vaccine only once. However, additional injections may be needed for young children who remain at high risk for meningococcal disease.
• Bexsero® and Trumenba® vaccine:
  • For prevention of meningococcal meningitis:
    • Adults and children 10 to 25 years of age:
      • Bexsero®: An injection is given into a muscle. Two doses, each given at least 1 month apart. It is very important for you or your child to receive all of the 2 shots for the vaccine. If you or your child misses a dose, call your or your child’s doctor for another appointment.
      • Trumenba®: An injection is given into a muscle. Three doses, each given several months apart, are necessary. It is very important for you or your child to receive all of the 3 shots for the vaccine. If you or your child misses a dose, call your or your child’s doctor for another appointment.

• It is used to prevent meningococcal disease.

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Pain where the shot was given.
• Irritation where the shot is given.
• Feeling tired or weak.
• Headache.
• Muscle or joint pain.
• Chills.
• Loose stools (diarrhea).
• Upset stomach.
• Fever.

These are not all of the side effects that may occur. If you have questions about side effects, call your doctor. Call your doctor for medical advice about side effects.

You may report side effects to the FDA at 1-800-FDA-1088. You may also report side effects at http://www.fda.gov/medwatch.

Applies to meningococcal group B vaccine: intramuscular suspension

General

The most common adverse events were pain at the injection site, fatigue, erythema, myalgia, headache, and induration.[Ref]

Local

Very common (10% or more): Injection site pain (92.8%), erythema (50%), induration (32%), swelling (21.6%)
Postmarketing reports: Blisters at or around injection site[Ref]

Nervous system

Very common (10% or more): Fatigue (64.4%), headache (56.9%), sleepiness, unusual crying
Uncommon (0.1% to 1%): Seizures (including febrile seizures)
Postmarketing reports: Syncope, vasovagal responses to injection[Ref]

Musculoskeletal

Very common (10% or more): Myalgia (49%), chills (30.3%), arthralgia (21.6%)[Ref]

Gastrointestinal

Very common (10% or more): Nausea (19%), diarrhea (15.2%)
Common (1% to 10%): Vomiting[Ref]

Psychiatric

Very common (10% or more): Irritability[Ref]

Metabolic

Very common (10% or more): Eating disorders[Ref]

Other

Common (1% to 10%): Fever[Ref]

Dermatologic

Common (1% to 10%): Rash
Uncommon (0.1% to 1%): Eczema
Rare (less than 0.1%): Urticaria[Ref]

Cardiovascular

Uncommon (0.1% to 1%): Pallor (rare after booster)
Rare (less than 0.1%): Kawasaki syndrome[Ref]

Hypersensitivity

Very rare (less than 0.01%): Anaphylaxis
Postmarketing reports: Allergic reactions, rash, eye swelling[Ref]

Respiratory

Frequency not reported: Nasopharyngitis[Ref]

Some side effects of Bexsero may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.

Safety and efficacy have not been established in patients younger than 10 years.

Consult WARNINGS section for additional precautions.

Administration advice:
-The deltoid muscle of the upper arm is the preferred injection site.

Storage requirements:
-Refrigerate; protect from light.
-Do not freeze. Discard if the vaccine has been frozen.

Reconstitution/preparation techniques:
-Shake vigorously to ensure a homogenous suspension.
-Do not use if the vaccine cannot be resuspended.