Benralizumab, an add-on treatment for severe eosinophilic asthma: evaluation of exacerbations, emergency department visits, lung function, and oral corticosteroid use

Figures & data

Table 1 Studies of benralizumab in asthma

Study	Study design	Number of patients	Population	Regimen	Main findings
Busse et al^Citation14	Phase I, open-label	44	Mild atopic asthmatics	Single, escalating IV dose	Reduction in peripheral eosinophils after 24 hours
Laviolette et al^Citation15	Phase I, multicenter, randomized, double-blind, placebo-controlled	27	Asthmatics, >2% sputum eosinophils, bronchodilator responsea	Single dose of benralizumab IV at dose of 1 mg/kg or placebo and 14 subjects were randomized to receive 100 mg, 200 mg or placebo subcutaneously	Reduction in eosinophil counts in the airway biopsies and peripheral blood eosinophils were undetectable at day 7. Bone marrow aspiration showed no eosinophils or precursors on day 28
Gossage et al^Citation16	Phase IIA, randomized, placebo-controlled	25	Adult asthmatics	3 monthly SC injections of benralizumab at 25, 100, or 200 mg or placebo on days 0, 28, and 56	Reduction in peripheral eosinophils
Castro et al^Citation17	Phase IIB, multicenter, randomized, double-blind, placebo-controlled	609	Uncontrolled asthmatics using medium-dose or high-dose ICS + LABA, with 2–6 exacerbations in the previous year	Benralizumab SC at 2 mg, 20 mg or 100 mg Q4 weeks first 3 doses followed by Q8 weeks for 1 year	Decrease in exacerbations in patients with blood eosinophils >300 cells/µL treated with 20 mg or 100 mg SC. No improvement in exacerbations was observed in participants without eosinophilia, even at the higher dose
Park et al^Citation18	Phase IIB, multicenter, randomized, double-blind, placebo-controlled	106	Uncontrolled eosinophilic asthma (>2% sputum eosinophils), using medium-dose or high-dose ICS + LABA, with 2–6 exacerbations in the previous year	Benralizumab SC at 2 mg, 20 mg or 100 mg Q4 weeks first 3 doses followed by Q8 weeks for 52 weeks	Reduction in exacerbations compared to placebo. In those with blood eosinophil >300 cells/µL the reduction in exacerbations was more pronounced
Nowak et al^Citation19	Phase IIA, multicenter, randomized, double-blind, placebo-controlled	110	Asthmatics presenting with an exacerbation and a previous exacerbation in the previous year	Single IV infusion of benralizumab of 0.3 mg/kg or 3 mg/kg or placebo 7 days after an exacerbation	Reduction in exacerbations and hospitalizations over 12 weeks
Bleecker et al^Citation20	Phase IIIA, multicenter randomized, parallel-group, placebo-controlled, double-blind	1,205	Uncontrolled asthmatics using medium-dose or high-dose ICS + LABA, bronchodilator responsea	Benralizumab 30 mg Q4 weeks or Q8 weeks (first 3 doses Q4) or placebo SC for 48 weeks	Patients with blood eosinophil counts >300 cells/µL had less exacerbations with benralizumab. Lung function improved in both the treatment groups, but symptoms only improved in the Q8 week regimen
FitzGerald et al^Citation21	Phase IIIA, multicenter randomized, parallel-group, placebo-controlled, double-blind	1,306	Uncontrolled asthmatics using medium-dose or high-dose ICS + LABA, bronchodilator responsea	Benralizumab 30 mg Q4 weeks or Q8 weeks (first 3 doses Q4) or placebo SC for 48 weeks	Patients with blood eosinophil counts >300 cells/µL had less exacerbations with benralizumab. Lung function improved in both the treatment groups, but symptoms only improved in the Q8 week regimen
Ferguson et al^Citation22	Phase IIIA, multicenter randomized, parallel-group, placebo-controlled, double-blind	221	Asthmatics on low-to-medium dosage ICS or low-dosage ICS + LABA	Benralizumab 30 mg Q4 weeks or placebo SC for 12 weeks	Mild improvement in lung function. No significant difference between those with and without eosinophilia
Nair et al^Citation23	Phase IIIA, multicenter randomized, parallel-group, placebo-controlled, double-blind	220	Asthmatics treated with OCS for at least 6 months with a blood eosinophil count of >150 cells/µL	Benralizumab 30 mg Q4 weeks or Q8 weeks (first 3 doses Q4) or placebo SC for 28 weeks	More patients were able to stop all OCS in the treatment group compared to placebo (50% vs 19%). Benralizumab resulted in reductions in exacerbations

Notes:

a Bronchodilator response: >12% increase in FEV₁ after inhalation of 400 mg of albuterol during screening or history of >12% FEV₁ reversibility within 1 year of randomization or history of 20% reduction in FEV₁ in response to a provocative methacholine challenge (PC20) of less than 8 mg/mL within 1 year of randomization.

Abbreviations: ICS, inhaled corticosteroids; IV, intravenous; LABA, long-acting β2-agonist; OCS, oral corticosteroid; Q4, every 4; Q8, every 8; SC, subcutaneously.

Table 2 FDA-approved monoclonal antibodies for severe asthma

Monoclonal antibody	Target	Dosing	Dosing calculation	Treatable traits
Omalizumab	IgE	SC every 2–4 weeks	IgE levels Weight	IgE levels (30–1,300 IU/dL) + Positive perennial allergens testing
Mepolizumab	IL-5	SC every 4 weeks	100 mg	Peripheral blood eosinophils >150 cells/µL
Reslizumab	IL-5	IV every 4 weeks	3 mg/kg	Peripheral blood eosinophils >400 cells/µL
Benralizumab	IL-5 receptor	SC every 8 weeks	30 mg every 8 weeks (first 3 doses every 4 weeks)	Peripheral blood eosinophils >300 cells/µL
Dupilumaba	IL-4 receptor	SC every 2 weeks	300 mg every 2 weeks (loading dose of 600 mg)	None specified

Note:

a Pending approval.

Abbreviations: IgE, immunoglobulin E; IV, intravenous; FDA, US Food and Drug Administration; SC, subcutaneously.

Table 3 Outcomes of oral corticosteroid-sparing trials in severe asthma

Outcome	SIRIUS^Citation28 (mepolizumab) N=69	ZONDA^Citation23 (benralizumab) N=145 (pooled)	VENTURE^Citation40 (dupilumab) N=103	SIRIUS (placebo) N=66	ZONDA (placebo) N=75	VENTURE (placebo) N=107
Median % dose reduction (IQ range)	−50 (20 to 75)	−75 (−100 to 100)	−100 (−100 to −62.5)	0 (−20 to 33)	25 (−150 to 100)	−50 (−100 to 0)
Dose at screening (mg)	12.5 (5 to 35)	10 (7.5 to 40)	10 (5 to 35)	15 (5 to 35)	10 (7.5 to 40)	10 (5 to 35)
Dose at end of optimization (mg)	10	10 (7.5 to 40)	10 (5 to 30)	12.5	10 (7.5 to 40)	10 (2 to 35)
100% reduction (%)	14	30	52	8	10	29
Final dose <5 mg (%)	54	60	71	32	33	37
No decrease (%)	36	22	31	56	47	13
Exacerbation reduction vs placebo (%)	32	55 to 75	59.3	–	–	–
Severe adverse events (%)	1	10	9	18	19	6
Death (n)	0	2	0	1	0	0

Abbreviation: IQ, interquartile.

Table 4 Exacerbation reduction of anti-IL-5 therapies in severe eosinophilic asthma

Anti-IL-5 therapy	Trials	Patients (n)	Reduction relative to placebo (%)
Benralizumab	SIROCCO^Citation20	809a	45–51a
	CALIMA^Citation21	728a	28–38a
	ZONDA^Citation23	145	55–75
Mepolizumab	DREAM^Citation26	621	39–52
	MENSA^Citation27	576	47–53
	SIRIUS^Citation28	145	32
Reslizumab	Castro et al^Citation34	953	50–59

Note:

a Patients with peripheral eosinophils >300 cells/µL.

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