FASENRA▼ benralizumab

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.1

Design of SIROCCO, CALIMA, ZONDA studies

SIROCCO (n=1,205)5,6

SIROCCO study design
SIROCCO study design

 

*Patients were also randomised to a third group that received FASENRA every 4 weeks (Q4W)5.

The recommended dose of FASENRA is 30 mg every 4 weeks for the first 3 doses, and then every 8 weeks thereafter.1

Primary endpoint: Annual exacerbation rate ratio vs placebo in patients receiving high-dose ICS + LABA with baseline blood eosinophils ≥300 cells/μL and ≥2 exacerbations in the prior year at week 48 (n=809).

Key secondary endpoints: Pre-bronchodilator FEV1 and total asthma symptom score at week 48.

Additional endpoints: Time to first exacerbation, AER associated with hospitalisation/ER visit, post-bronchodilator FEV, ACQ-6 score and AQLQ score.

Inclusion criteria: Patients aged 12–75 years**, 40kg or heavier in weight, and who were diagnosed by a physician to have had asthma needing treatment with medium-dosage or high-dosage ICS + LABA for at least 1 year before enrolment; ≥2 asthma exacerbations needing systemic corticosteroid treatment or a temporary increase in usual maintenance dosages of oral corticosteroids within 1 year before enrolment; ICS + LABA with or without OCS and additional asthma controllers for at least 3 months before enrolment; pre-bronchodilator FEV1 of <80% predicted at screening, a documented post-bronchodilator reversibility of at least 12% and at least 200 mL in FEV1 within 12 months before enrolment or identified at screening and an ACQ-6 score of at least 1 – 5 at enrolment

Exclusion criteria: A history of anaphylaxis with any biologic drug, a clinically important pulmonary disease other than asthma, or a helminthic parasitic infection diagnosed within 24 weeks before enrolment that had either not been treated or did not respond to standard-of-care treatment

Definition of an exacerbation: An exacerbation was defined as a worsening of asthma that led to one of the following: (1) The use of systemic corticosteroids, or a temporary increase in a stable oral corticosteroid background dosage, for at least 3 days or a single injectable dose of corticosteroids; (2) Visit to an emergency department or to an urgent care centre (<24h) because of asthma that needed systemic corticosteroids; or (3) An inpatient hospital stay (≥24h) because of asthma. The worsening of asthma was defined as any new or increased symptoms or signs that were concerning to the patient or related to an Asthma Daily Diary alert. 

**Fasenra is indicated in adult patients greater than 18 years of age.

CALIMA (n=1,306)9,10

CALIMA study design
CALIMA study design

 

*Patients were also randomised to a third group that received FASENRA every 4 weeks (Q4W)9.

The recommended dose of FASENRA is 30 mg every 4 weeks for the first 3 doses, and then every 8 weeks thereafter.1

Primary endpoint: Annual exacerbation rate ratio vs placebo for patients receiving high-dose ICS + LABA with baseline blood eosinophils ≥300 cells/μL and ≥2 exacerbations in the prior year at 56 weeks (n=728).

Key secondary endpoints: Pre-bronchodilator in FEV1 and total asthma score.

Additional endpoints: Time to first exacerbation, AER associated with hospitalisation/ER visit, post-bronchodilator FEV1, ACQ-6 score and AQLQ score.

Inclusion criteria: Patients aged 12 – 75 years** 40kg or heavier in weight, with a history of physician-diagnosed asthma requiring treatment with medium-dose to high‑dose ICS + LABA (>250 μg [medium] or ≥500 μg [high] per day fluticasone propionate dry powder formulation or equivalent total daily dosage) for 12 months or more before enrolment ; ≥2 asthma exacerbations in the 12 months before enrolment that required use of a systemic corticosteroid or temporary increase in the patient’s usual maintenance dosage of OCS; Additional inclusion criteria included treatment with inhaled corticosteroids (≥500 μg per day fluticasone propionate dry powder formulation or equivalent total daily dosage) + LABA for 3 months or more before enrolment, with or without oral corticosteroids and additional asthma controllers; a pre-bronchodilator FEV1 <80% predicted at screening, ACQ-6 score ≥1·5 at enrolment and post-bronchodilator reversibility in FEV1 of 12% or greater and 200 mL or greater in FEV1 within 12 months before enrolment. 

Exclusion criteria: Clinically important pulmonary disease other than asthma; history of anaphylaxis to any biologic therapy; a helminthic parasitic infection that had not been treated with, or had failed to respond to, standard-of-care therapy; acute upper or lower respiratory infections requiring antibiotics or antiviral medication within 30 days prior to the date informed consent. 

Definition of an exacerbation: An asthma exacerbation was defined as a worsening of asthma that led to one of the following: (1) The use of systemic corticosteroids for 3 days or more or a temporary increase in a stable, background dosage of oral corticosteroids; (2) Visit to an emergency department or to an urgent care visit (<24 h) due to asthma that required systemic corticosteroids; or (3) An inpatient admission to hospital (≥24 h) due to asthma. The worsening of asthma was defined as any new or increased symptoms or signs that were concerning to the patient or related to an Asthma Daily Diary alert.

**Fasenra is indicated in adult patients greater than 18 years of age.

 

ZONDA (n=220)7,8

ZONDA study design
ZONDA study design

 

*Patients were also randomised to a third group that received FASENRA every 4 weeks (Q4W) 7,8

The recommended dose of FASENRA is 30 mg every 4 weeks for the first 3 doses, and then every 8 weeks thereafter.1

Primary endpoint: Percentage reduction in the oral glucocorticoid dose from baseline (randomisation at week 0) to the final dose at the end of the maintenance phase (week 28) while asthma control was maintained.

Key secondary endpoints: Annual exacerbation rate, time to first exacerbation and FEV1.

Additional endpoints: Exacerbations associated with hospitalisation/ER visit, pre-bronchodilator FEV1, total asthma symptom score, ACQ-6 score and the AQLQ score.

Inclusion criteria: Blood eosinophil count of ≥150 cells/mm3 and asthma that had been treated with medium-dose to high-dose inhaled glucocorticoid + LABA therapy for ≥12 months before enrolment and treated with high-dose inhaled glucocorticoid + LABA therapy for ≥6 months before enrolment; oral glucocorticoid therapy for ≥6 continuous months directly before enrolment. 

Exclusion criteria: Clinically important pulmonary disease other than asthma; history of anaphylaxis to any biologic therapy; a helminth parasitic infection diagnosed within 24 weeks prior to enrolment that had not been treated with, or had failed to respond to, standard-of-care therapy; acute upper or lower respiratory infections requiring antibiotics or antiviral medications within 30 days prior to enrolment or during the run-in/oral glucocorticoid optimisation phase.

Definition of an exacerbation: An asthma exacerbation was defined as worsening of asthma that led to a temporary increase in the systemic glucocorticoid dose for at least 3 days to treat the symptoms, an emergency department visit resulting from asthma that led to treatment with a systemic glucocorticoid in addition to the patient’s regular maintenance medications, or an inpatient hospitalisation because of asthma.