Benralizumab

Registered South African indications:

• Indicated as an add-on maintenance treatment in adult patients with severe eosinophilic asthma inadequately controlled despite high-dose inhaled corticosteroids plus long-acting β-agonists

Contraindications

Registered contraindications in South Africa & other jurisdictions

• Hypersensitivity to the active ingredient or to any of the excipients

Cautions

Recommendations in South Africa & other jurisdictions

Caution in the following patient groups

• Pregnancy
• Breastfeeding
• Fertile women not practising effective contraception (South African recommendations)

Asthma exacerbations

• Benralizumab should not be used to treat acute asthma exacerbations. Patients should be instructed to seek medical advice if their asthma remains uncontrolled or worsens after initiation of treatment

Corticosteroids

• Abrupt discontinuation of corticosteroids after initiation of benralizumab therapy is not recommended. Reduction in corticosteroid doses, if appropriate, should be gradual and performed under the supervision of a physician

Hypersensitivity reactions

• Acute systemic reactions including anaphylactic reactions and hypersensitivity reactions have occurred following administration of benralizumab. These reactions may occur within hours of administration, but in some instances have a delayed onset (i.e. days)
• A history of anaphylaxis unrelated to benralizumab may be a risk factor for anaphylaxis following benralizumab administration. In line with clinical practice, patients should be monitored for an appropriate duration after administration of benralizumab
• In the event of a hypersensitivity reaction, benralizumab should be discontinued permanently and appropriate therapy initiated

Parasitic (helminth) infection

• Eosinophils may be involved in the immunological response to some helminth infections. Patients with known helminth infections were excluded from participation in clinical trials. It is unknown if benralizumab may influence a patient's response against helminth infections
• Patients with pre-existing helminth infections should be treated before initiating therapy with benralizumab. If patients become infected, while receiving treatment and do not respond to anti-helminth treatment, therapy with benralizumab should be discontinued until infection resolves

Traceability (Recommendations in other jurisdictions)

• In order to improve the traceability of biological medicinal products, the name and the batch number of the administered product should be clearly recorded

Forms avail. in SA and covered in this monograph: pfp

South African registered indications and dosages

Treatment should be initiated by a medical practitioner experienced in the diagnosis and treatment of severe asthma

Add-on maintenance treatment for severe eosinophilic asthma in patients inadequately controlled with high-dose inhaled corticosteroids and long-acting β-agonists

• SC: Initial: 30mg, every 4 weeks for the first 3 doses; Maintenance: 30mg, every 8 weeks thereafter; Treatment duration: Intended for long-term treatment

After proper training in subcutaneous injection techniques and education on the signs and symptoms of hypersensitivity reactions, patients with no known history of anaphylaxis or their caregivers may administer benralizumab, if deemed appropriate by their medical practitioner, with necessary medical follow-up. Self-administration should only be considered for patients already experienced with benralizumab treatment

Missed dose: If a dose is missed on the planned date, resume dosing as soon as possible on the indicated regimen; do not administer a double dose

Benralizumab is intended for long-term treatment. Continuation of therapy should be evaluated at least annually, based on disease severity, level of exacerbation control, and blood eosinophil counts

Method of administration
Benralizumab is administered as a subcutaneous injection. It should be injected into the thigh or abdomen. If the healthcare professional or caregiver administers the injection, the upper arm can also be used. It should not be injected into areas where the skin is tender, bruised, erythematous, or hardened. Comprehensive instructions for administration using the pre-filled pen can be referred to in the ‘Instructions for Use’ that is available in the product packaging

Not established for use

No data are available for children aged 6 to 11 years old. Data currently available in children 12 to less than 18 years old, but no recommendation on a posology can be made

Pregnancy

Recommendations below are applicable to South Africa and other jurisdictions

• Caution; not recommended
• Safety in pregnancy has not been established
• There is a limited amount of data (less than 300 pregnancy outcomes) from the use of benralizumab in pregnant women
• Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity
• Monoclonal antibodies, such as benralizumab, are transported across the placenta linearly as pregnancy progresses; therefore, potential exposure to a foetus is likely to be greater during the second and third trimester of pregnancy
• As a precautionary measure, it is preferable to avoid the use of benralizumab during pregnancy. Its administration to pregnant women should only be considered if the expected benefit to the mother is greater than any possible risk to the foetus

Breastfeeding

South African recommendations

• Caution; not recommended
• Safety in lactation has not been established, hence, the patient should not breastfeed while on benralizumab, unless the benefit of therapy to the woman outweighs the risk to the child

Recommendations in other jurisdictions

• Caution
• It is unknown whether benralizumab or its metabolites are excreted in human or animal milk. A risk to the breast-fed child cannot be excluded
• A decision must be made whether to discontinue breastfeeding or to discontinue/abstain from using benralizumab taking into account the benefit of breast-feeding for the child and the benefit of therapy for the woman

Fertility

South African recommendations

• Safety has not been established in fertile patients, hence benralizumab should not be administered to fertile women not practising effective contraception

Recommendations in other jurisdictions

• There are no fertility data in humans. Animal studies showed no adverse effects of benralizumab treatment on fertility

Recommendations below are applicable to South Africa and other jurisdictions

• No dose adjustment recommended

Recommendations below are applicable to South Africa and other jurisdictions

• No dose adjustment recommended

Recommendations below are applicable to South Africa and other jurisdictions

• No dose adjustment recommended

Infections and infestations

Common

• Pharyngitis
  - Bacterial pharyngitis
  - Viral pharyngitis
  - Streptococcal pharyngitis

Immune system disorders

Common

• Hypersensitivity reactions
  - Urticaria
  - Papular urticaria
  - Rash

Frequency not known

• Anaphylactic reaction

Nervous system disorders

Common

• Headache

General disorders and administration site conditions

Common

• Pyrexia
• Injection site reaction
  - Pain
  - Erythema
  - Pruritus
  - Papule

• None known

• Pulmonary function
• Peak flow
• Blood eosinophil count

Additional observations

• Signs of infection
• Anaphylaxis or hypersensitivity reactions (during and after administration)

Benralizumab is an anti-eosinophil, humanised afucosylated, monoclonal antibody (IgG1, kappa). It specifically binds to the alpha subunit of the human interleukin-5 receptor (IL-5Rα ). The IL-5 receptor is specifically expressed on the surface of eosinophils and basophils. The absence of fucose in the Fc domain of benralizumab results in high affinity for Fcɣ RIII receptors on immune effector cells such as natural killer (NK) cells. This leads to apoptosis of eosinophils and basophils through enhanced antibody-dependent cell-mediated cytotoxicity (ADCC), which reduces eosinophilic inflammation.