The document summarizes two clinical trials - SIROCCO and CALIMA - that evaluated the efficacy and safety of benralizumab in treating severe asthma. Both trials found that benralizumab significantly reduced annual asthma exacerbation rates in patients with high baseline eosinophil counts who were uncontrolled on standard treatment. SIROCCO saw greater efficacy than CALIMA, possibly due to regional differences. Adverse events were also reported. The trials demonstrated benralizumab's potential as an additional treatment option for severe eosinophilic asthma.

1. A COMPARISON BETWEEN
SIROCCO AND CALIMA TRIAL
Efficacy and Safety Study of
Benralizumab in Adults and
Adolescents Inadequately Controlled
on Inhaled Corticosteroid Plus Long-
acting β2 Agonist
PREPARED BY
DR POOJA HURKAT
Ph.D (Pharmaceutical Biotechnology)
8989977484
pooja159@gmail.com

2. J.B. Bice et al. / Ann Allergy Asthma Immunol 112 (2014) 108e115.
Mechanism of Action of Anti-Asthmatic Drugs

3. SIROCCO : Randomized, Multicenter, placebo-controlled , phase 3 study
Bleecker ER, et al.Lancet 2016; 388: 2115–27
CONCLUSION
• The study confirmed the efficacy and safety of
benralizumab for severe asthma and elevated eosinophils,
which are uncontrolled by high-dosage ICS plus LABA
(additional option)
• Clinical efficacy related to baseline blood eosinophil counts,
similar in mepolizumab and reslizumab studies
• Q8W dosage was efficacious: potential to lower disease
burden and reduce costs
• Severe uncontrolled
asthmatics
• Age 12-75 years, M/F,wt: 40 kg
• N=1205
Benralizumab
30 mg SC Q4W
N= 399
Benralizumab
30 mg SC Q4W for
3 doses then Q8W
N= 398
INCLUSION CRITERIA
i. Diagnosis of asthma for at least 1 year and
at least 2 exacerbations while on high-
dosage ICS plus LABA in previous year (
documented for atleast 3 months before
enrollment).
ii. ≥ 18 yrs pt on high dose ICS
iii.12-17 yrs pt on high or medium dose ICS
EXCLUSION CRITERIA
i. History of Anaphylaxis with active
Biologic drug
ii. Pulmonary disease other than Asthma
iii.Helminthic parasitic infection
diagnosed within 24 weeks before
enrolment that had either not been
treated or did not respond to standard-
of-care treatment.
Placebo
Q4W for 48
weeks
N= 407
≥ 300 µl/mL
< 300 µl/mL
2:12:1
ARMS AND INTERVENTION
(Randomization)
STRATIFICATION OF PATIENTS
BASED ON EOSINOPHIL COUNT
< 300 µl/mL
2:1
≥ 300 µl/mL
< 300 µl/mL
≥ 300 µl/mL
END POINT
PRIMARY ENDPOINT
• Annual exacerbation rate ratio at
48 weeks versus placebo
SECONDARY ENDPOINT
1.Pre-bronchodilator forced expiratory
volume in 1 s (FEV1)
2. Total asthma symptom score at week
48, for patients with blood eosinophil
counts of at least 300 cells per μL.
1:1:1
ICS=inhaled corticosteroids. LABA=long-acting â2-agonist. Q4W=every 4 weeks. Q8W=every 8 weeks (first three
doses Q4W).
48 weeks
Adverse Events
374 sites, 17 countries
High-dosage ICS plus LABA with baseline blood
eosinophils ≥300 cells per μL (n=809)
High-dosage ICS plus LABA with baseline
blood eosinophils <300 cells per μL (n=395)

4. CALIMA: Randomized, Multicenter, double blind, placebo controlled phase 3 trial
EXCLUSION CRITERIA
i. Pt with Clinically important pulmonary disease
other than asthma .
ii.Any disorder or major physical impairment
which may affect safety or pt ability to continue
study or influence study finding or interpretation..
iii.Acute upper or lower respiratory infections
requiring antibiotics or antiviral medication
within 30 days prior to the date informed consent
is obtained or during the screening/run-in period.
iv.Any clinically significant abnormal findings
FitzGerald JM et al. Lancet 2016; 388: 2128–41
56 Weeks
Severe Uncontrolled Asthmatics
Age 12-75 years, M/F, wt: ≥ 40
kg
N=1306
INCLUSION CRITERIA
Pt on medium-to-high dose ICS (>250µg
fluticasone dry powder formulation equivalents
total daily dose) and a LABA, for at least 12
months prior to Visit 1
Documented treatment with ICS and LABA for
at least 3 months prior to Visit 1 with or without
oral corticosteroids and additional asthma
controller
Benralizumab 30 mg SC
Q4W
N=425
Benralizumab30 mg SC
Q4W for 3 doses then
Q8W
N=441
Placebo
N=440
2:12:12:1
1:1:1
≥ 300 µl/mL
< 300 µl/mL
< 300 µl/mL
≥ 300 µl/mL
< 300 µl/mL
≥ 300 µl/mL
ARMS AND INTERVENTION
(RANDOMIZATION)
STRATIFICATION OF
PATIENTS BASED ON
EOSINOPHIL COUNT
END POINT
PRIMARY ENDPOINT
Annual exacerbation rate ratio at 48
weeks versus placebo
SECONDARY END POINT
Pre-bronchodilator FEV1 and total
Asthma symptom score for patient
receiving high dosage ICS+ LABA with
baseline blood eosinophil ≥ 300 µl/mL
303 sites in
11 countries
CONCLUSION
• The study showed that 56 weeks of add-on therapy with
benralizumab30 mg Q4W and Q8W significantly reduced
the annual rate of asthma exacerbations by up to 36% for
patients with severe asthma and elevated blood eosinophils.
• Confirm and support SIROCCO study, but efficacy less
than SIROCCO-possible regional heterogeneity
High-dosage ICS plus LABA with baseline blood
eosinophils ≥300 cells per μL (n=728).
High-dosage ICS plus LABA with baseline blood
eosinophils <300 cells per μL (n=363)
ADVERSEEVENTS

5. OUTCOME SIROCCO CALIMA
PRIMARY
ENDPOINT
Annual asthma
exacerbation rate
estimates at 48
weeks according
to baseline blood
eosinophil
concentrations
(eosinophils ≥300
cells per μL )
SECONDARY
ENDPOINT
Change from
baseline in pre-
bronchodilator
forced expiratory
volume in 1 s
according to
baseline
blood eosinophil
concentrations
(eosinophils ≥300
cells per Μl)
ADVERSE
EVENT(S)
FitzGerald JM et al. Lancet 2016; 388: 2128–41
BleeckerER, et al.Lancet 2016;388:2115–27

6. Efficacy results for patients who received high-dosage inhaled corticosteroids plus long-acting
β2-agonists with baseline blood eosinophils at least 300 cells per μL in the CALIMA and SIROCCO studies
SIROCCO CALIMA
Benralizumab
Q4W
Benralizumab
Q8W
Benralizumab
Q4W
Benralizumab
Q8W
Annual rate of
exacerbations
↓ 45% ↓ 51% ↓ 36% ↓ 28%
Pre-bronchodilator
FEV1 (L)
↑ 0·106 ↑ 0·159 ↑ 0·125 ↑ 0·116
Total asthma
symptom score
(score 0–6)*
↓ 0·08† ↓ 0·25 ↓ 0·12† ↓ 0·23
All results are differences from placebo; week 48 results for SIROCCO and week 56 results for
CALIMA.
FEV1=forced expiratory volume in 1 s.
Q4W=every 4 weeks. Q8W=every 8 weeks (first three doses Q4W).
*Reduced score suggests improvement. †Non-significant.
FitzGerald JM et al. Lancet 2016; 388: 2128–41Bleecker ER, et al.Lancet 2016;388: 2115–27

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