4.1. Therapeutic indications

Asthma

Fasenra is 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 (see section 5.1).

Eosinophilic granulomatosis with polyangiitis (EGPA)

Fasenra is indicated as an add-on treatment for adult patients with relapsing or refractory eosinophilic granulomatosis with polyangiitis (see section 5.1).

4.2. Posology and method of administration

Fasenra treatment should be initiated by a physician experienced in the diagnosis and treatment of conditions for which benralizumab is indicated (see section 4.1).

After proper training in the subcutaneous injection technique and education about signs and symptoms of hypersensitivity reactions (see section 4.4), patients with no known history of anaphylaxis or their caregivers may administer Fasenra if their physician determines that it is appropriate, with medical follow-up as necessary. Self-administration should only be considered in patients already experienced with Fasenra treatment.

Posology

Fasenra is intended for long‑term treatment. A decision to continue the therapy should be made at least annually based on disease severity, level of disease control and blood eosinophil counts.

Asthma

The recommended dose of benralizumab is 30 mg by subcutaneous injection every 4 weeks for the first 3 doses, and then every 8 weeks thereafter.

EGPA

The recommended dose of benralizumab is 30 mg by subcutaneous injection every 4 weeks.

Patients who develop life-threatening manifestations of EGPA should be evaluated for the need for continued therapy, as Fasenra has not been studied in this population.

Missed Dose

If an injection is missed on the planned date, dosing should resume as soon as possible on the indicated regimen; a double dose must not be administered.

Elderly

No dose adjustment is required for elderly patients (see section 5.2).

Renal and hepatic impairment

No dose adjustment is required for patients with renal or hepatic impairment (see section 5.2).

Paediatric population

The safety and efficacy of Fasenra in children and adolescents aged 6 to 17 years with asthma has not been established. Currently limited data in children 6 to 11 years old and data in adolescents aged 12 to 17 are described in sections 4.8, 5.1 and 5.2 but no recommendation on a posology can be made.

The safety and efficacy of Fasenra in children less than 6 years with asthma have not been established. No data are available.

The safety and efficacy of Fasenra in children and adolescents less than 18 years with EGPA have not been established.

Method of administration

This medicinal product 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 are provided in the 'Instructions for Use'.

4.3. Contraindications

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

4.4. Special warnings and precautions for use

Traceability

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

Asthma exacerbations

Fasenra 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 Fasenra 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 (e.g. urticaria, papular urticaria, rash) have occurred following administration of benralizumab (see section 4.8). 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 Fasenra administration (see section 4.3). In line with clinical practice, patients should be monitored for an appropriate time after administration of Fasenra.

In the event of a hypersensitivity reaction, Fasenra should be discontinued permanently and appropriate therapy should be 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.

Organ threatening or life-threatening EGPA

Fasenra has not been studied in patients with active organ threatening or life-threatening manifestations of EGPA (see section 4.2).

4.5. Interaction with other medicinal products and other forms of interaction

No interaction studies have been performed. In a randomised, double‑blind parallel‑group study of 103 patients aged between 12 and 21 years with severe asthma, the humoral antibody responses induced by seasonal influenza virus vaccination do not appear to be affected by benralizumab treatment. An effect of benralizumab on the pharmacokinetics of co‑administered medicinal products is not expected (see section 5.2).

Cytochrome P450 enzymes, efflux pumps and protein‑binding mechanisms are not involved in the clearance of benralizumab. There is no evidence of IL‑5Rα expression on hepatocytes. Eosinophil depletion does not produce chronic systemic alterations of proinflammatory cytokines.

4.6. Fertility, pregnancy and lactation

Pregnancy

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 (see section 5.3).

Monoclonal antibodies, such as benralizumab, are transported across the placenta linearly as pregnancy progresses; therefore, potential exposure to the fetus 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 Fasenra 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 fetus.

Breast‑feeding

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 breast‑feeding or to discontinue/abstain from using Fasenra taking into account the benefit of breast‑feeding for the child and the benefit of therapy for the woman.

Fertility

There are no fertility data in humans. Animal studies showed no adverse effects of benralizumab treatment on fertility (see section 5.3).

4.7. Effects on ability to drive and use machines

Fasenra has no or negligible influence on the ability to drive and use machines.

4.8. Undesirable effects

Summary of the safety profile

The safety profile of benralizumab in asthma and EGPA are similar.

The most commonly reported adverse reactions during treatment in asthma are headache (8%) and pharyngitis (3%). The most commonly reported adverse reaction in EGPA is headache (17%). Cases of anaphylactic reaction of varied severity have been reported for benralizumab.

Tabulated list of adverse reactions

The following adverse reactions have been reported with benralizumab during clinical studies in asthma and EGPA and from post-marketing experience.

The frequency of adverse reactions is defined using the following convention: very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1,000); very rare (<1/10,000); and not known (cannot be estimated from available data). Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness.

Table 1 . Tabulated list of adverse reactions

MedDRA System organ class

Adverse reaction

Frequency

Infections and infestations

Pharyngitisa

Common

Immune system disorders

Hypersensitivity reactionsb

Anaphylactic reaction

Common

Not known

Nervous system disorders

Headachec

Common

General disorders and administration site conditions

Pyrexia

Injection site reactiond

Common

a Pharyngitis was defined by the following grouped preferred terms: 'Pharyngitis', 'Pharyngitis bacterial', 'Viral pharyngitis', 'Pharyngitis streptococcal'. b Hypersensitivity reactions were defined by the following grouped preferred terms: 'Urticaria', 'Papular urticaria', and 'Rash'. For examples of the associated manifestations reported and a description of the time to onset, see section 4.4. c Very common in EGPA study.

d See 'Description of selected adverse reaction'.

Description of selected adverse reaction

Injection site reactions

In placebo‑controlled asthma studies, injection site reactions (e.g. pain, erythema, pruritus, papule) occurred at a rate of 2.2% in patients treated with the recommended benralizumab dose compared with 1.9% in patients treated with placebo. The events were transient in nature.

Long-term safety

In a 56-week extension trial (Trial 4) in patients with asthma from Trials 1, 2 and 3, 842 patients were treated with Fasenra at the recommended dose and remained in the trial. The overall safety profile was similar to the asthma trials described above. Additionally, in an open-label safety extension trial (Trial 5) in patients with asthma from previous trials, 226 patients were treated with Fasenra at the recommended dose for up to 43 months. Combined with the treatment period in previous studies, this corresponds to a median follow-up of 3.4 years (range 8.5 months – 5.3 years). The safety profile during this follow-up period was consistent with the known safety profile of Fasenra.

Paediatric population

There are limited data in paediatric patients. There were 108 adolescents aged 12 to 17 with asthma enrolled in the phase 3 trials (Trial 1: n=53, Trial 2: n=55). Of these, 46 received placebo, 40 received benralizumab every 4 weeks for 3 doses, followed by every 8 weeks thereafter, and 22 received benralizumab every 4 weeks. Adolescent patients aged 12 to 17 (n=86) from Trials 1 and 2 continued the treatment with benralizumab in Trial 4 for up to 108 weeks. The frequency, type and severity of adverse reactions in the adolescent population were observed to be similar to those seen in adults.

In an open-label, uncontrolled pharmacokinetic and pharmacodynamic study of 48 weeks duration in a limited number of paediatric patients (n=28) with uncontrolled severe asthma, the safety profile for patients aged 6 to 11 years old was similar to the adult and adolescent population (see section 4.2).

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme; website: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

4.9. Overdose

Doses of up to 200 mg were administered subcutaneously in clinical trials to patients with eosinophilic asthma without evidence of dose‑related toxicities.

There is no specific treatment for an overdose with benralizumab. If overdose occurs, the patient should be treated supportively with appropriate monitoring as necessary.