Benralizumab

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. Reduction in corticosteroid dose may be associated with systemic withdrawal symptoms and/or unmask conditions previously suppressed by systemic corticosteroid therapy.

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.

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 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 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 fetus.

It is unknown whether benralizumab or its metabolites are excreted in human or animal milk. 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 benralizumab 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.

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

Summary of the safety profile

The most commonly reported adverse reactions during treatment are headache (8%) and pharyngitis (3%). Cases of anaphylactic reaction of varied severity have been reported.

Tabulated list of adverse reactions

The following adverse reactions have been reported with benralizumab during clinical studies 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.

Tabulated list of adverse reactions:

^* Pharyngitis was defined by the following grouped preferred terms: ‘Pharyngitis’, ‘Pharyngitis bacterial’, ‘Viral pharyngitis’, ‘Pharyngitis streptococcal’.
^** 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 ‘Description of selected adverse reaction’.

Description of selected adverse reaction

Injection site reactions

In placebo-controlled 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 benralizumab 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 benralizumab 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 benralizumab.

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 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.