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3
What is asthma?
► Allergic asthma
► Non-allergic asthma
► Late-onset asthma
► Asthma with fixed airflow limitation
► Asthma with obesity
1. Bollag U, et al. Fam Pract 2009;26:96–101; 2. World Health Organization. Global surveillance, prevention and control
of chronic respiratory diseases. Available from: www.who.int; ; 3. Accordini S, et al. Allergy 2008;63:116–24; 4. Leynaert B, 7
et al. Thorax 2012;67:625–31.
Risk of asthma is related to the
level of serum IgE
40
n=2,657
Asthma (odds ratio)*
20
10
5.0
2.5
1.0
No. of
Total people with Prevalence of
population asthma clinical asthma
Region (millions) (millions) (%)
Central Asia and
224.7 9.7 4.3
Pakistan
Southern Asia 1,210.0 42.2 3.5
China/Taiwan/Mongolia 1,324.1 27.8 2.1
Northeast Asia 196.8 11.4 5.8
Southeast Asia 529.3 17.5 3.3
Oceania 30.7 4.5 14.6
1. 1.Masoli M, et al. Global burden of asthma report, 2004. Available from: www.ginasthma.org/documents/8 9
GINA definition of asthma severity
(2005)
Moderate Severe
Intermittent Mild persistent persistent persistent
More than once
Less than once
Symptoms a week but less Daily Daily
a week
than once a day
May affect May affect activity
Exacerbations Brief Frequent
activity and sleep and sleep
Nocturnal Not more than More than twice More than once
Frequent
symptoms twice a month a month a week
Limitation of
Daily use of inhaled
Other No No physical
SABA
activities
FEV1 or PEF
≥80% ≥80% 60–80% ≤60%
(% predicted)
FEV1 or PEF
<20% 20–30% >30% >30%
variability
FEV1 = forced expiratory volume in 1 second; GINA = Global Initiative for Asthma; PEF = peak expiratory flow;
SABA =short-acting β2-agonist
Moderate (n=2,285)
15 Severe (n=2,285)
11
10
10
6
5 3
1
0
Emergency department Hospitalization
visit
12
10
8
6
4
2
0
Intubation ICU admission In-hospital mortality
*All patients were admitted following an exacerbation.
ICU = intensive care unit.
Controlled (n=216)
Mean †
*
13.6 Uncontrolled (n=3,700)
14 **
12.0
12
***
10.0
10
6
3.8
4
** ***
2 1.4 1.3 1.1
0.3 0 0
0
Work days School days Physician Hospital ED
lost lost visits nights visits
*p<0.05; **p<0.01; ***p<0.001; †in previous year.
ED = emergency department.
80
69
62
60
40 38
31
20
0
Salmeterol/fluticasone Salmeterol/fluticasone
plus course of oral corticosteroids
*>500–1,000 µg BDP or equivalent at entry
Bateman E, et al. Am J Respir Crit Care Med 2004
17
Severe Asthma patients with the
greatest unmet need
Patient
Patients with severe persistent asthma who
Type remain symptomatic despite treatment with
high-dose ICS and LABA and one or more of the
following :
– are identified as high risk for asthma-related mortality
– have ≥2 severe exacerbations per year
– require ≥3 courses of OCS per year
– have regular disruptive nocturnal or daytime symptoms
– have severely restricted their lives in an effort to avoid
symptoms and exacerbations
18
TOPIC PRESENTATION
► Epidemiology & Burden of disease of Asthma
► Asthma Severity & Current management of asthma
► Pathophysiology Allergic Asthma &
Xolair® (Omalizumab) Mechanism of Action
► Xolair® (Omalizumab) : Indication & Phase III Clinical Study
► Xolair® (Omalizumab) : Treatment evaluation & Safety
Profile
► Summary
19
Xolair® (Omalizumab) as Anti-IgE:
Mechanism in Allergic Asthma
Reduces allergy chemicals release
B lymphocyte Allergic
Inflammation:
Allergic eosinophils and
-switch mediators lymphocytes
Plasma cell
Release
of IgE Clinical
Allergens Exacerbation
► ‘Humanization’ process
ensures that residues of
murine origin constitute less
than 5% of the omalizumab
molecule
– Minimizing the potential
for an immune response
IgE/G = immunoglobulin E/G.
22
Xolair® Approved Indication in
Asthma
Omalizumab is indicated as add on therapy to improve asthma
control in adult, adolescent patients (12 years of age and older)
and children (6 to 12 years of age) with :
Severe persistent allergic asthma
Positive skin test or in vitro reactivity to a perennial aeroallergen
Reduced lung function (FEV1 < 80%)
Frequent daytime symptoms or night-time awakenings
Multiple documented severe asthma exacerbations despite high
dose inhaled corticosteroid plus long-acting beta2-agonist
Treatment should only be considered for patients with convincing
IgE mediated asthma
p<0.002
0.5 Relative reduction in
0.48 severe asthma
0.4 50% exacerbations*^
REDUCTION
(28 weeks)
0.3
*. Severe asthma exacerbations in this
0.2 study were defined as when a
0.18#
0.29†
0.5 0.40** 0.42§
0.70**
1.0
1. Ayres JG, et al. Allergy 2004; 2. Vignola AM, et al. Allergy 2004
1.5 3. Busse W, et al. J Allergy Clin Immunol 2001
1.49** 4. Solèr M, et al. Eur Respir J 2001
**p0.001; †p=0.027; #p=0.077; §p=0.165 5. Holgate ST, et al. Clin Exp Allergy 2004
25
Innovate Study : Significant Improvement
in Lung Function (FEV1)
INNOVATE :
Randomized double-blind clinical study
P=0.043
200
FEV1 (% predicted) was
Improvement from baseline in FEV1 (ml)
22 L/MIN
Meta-analysis of three randomized clinical study
p= 0.026 XOLAIR® vs placebo
IMPROVEMENT
n=135
22L/min In morning peak expiratory
flow rate after 16 weeks vs
baseline
12L/min (p=0.045)
n=11
10 L/min
12 L/MIN
9
IMPROVEMENT
In morning peak expiratory
flow rate after 16 weeks vs
placebo
(p=0.026)
study
0.5
P=0.038
0.45 RELATIVE REDUCTION IN
0.4 EMERGENCY ROOM
0.43
0.35 44% VISITS1^
REDUCTION
0.3 In a separate real-word
0.25 questionnaire based
study, adding XOLAIR® to
0.2
standard of care
0.15 0.24 reduced emergency
0.1
room visits by 65%2*
0.05 BSC = Base Standard Care, as defined by NHLBI
0 guidelines; moderate to high dose : ICS+/- LABA,
with systemic Corticosteroid allowed in the most
BSC* group XOLAIR®+ BSC sever patients
(n=106) group (n=206)
1. Humbert M et al. Benefits of omalizumab as add-on therapy in patients with severe persistent asthma who are inadequately controlled
despite (GINA step 4 treatment) : INNOVATE. Allergy 2005: 60:309-316 28
2. Molimard M et al. Effectiveness of Omalizumab in the first patients treated in real life practice in France. Respiratory Medicine 2008; 102:71-6
Xolair® : Reduces Severe Allergic Asthma-
Related Hospitalizations
67%
EXALT : Open-label study
Mean hospitalisation rate
(32 week treatment period) SIGNIFICANT REDUCTION IN
ASTHMA-RELATED
OAT (n=128)
HOSPITALISATIONS
P=0.037
0.14
Additionally, mean total
number of emergency visits
due to an exacerbation was
significantly reduced by 58%
XOLAIR® + OAT (n=272) with XOLAIR® +OAT vs OAT
(Optimized asthma therapy)
alone over the 32 week
0.05 treatment period (p≤ 0.001)
Bousquet J et al. Persistency of response to omalizumab therapy in severe allergic (IgE mediated)
asthma. Allergy 2011 ; 66: 671-8. 29
Xolair® : Reduces the daytime and night
time symptoms of severe allergic asthma
86%
RELATIVE REDUCTION IN
NIGHT-TIME SYMPTOMS
p<0.001
Korn S et al. Omalizumab in patients with severe persistent allergic asthma in a real life setting in Germany. Respiratory Medicine 2009;
103:1725-31 30
Xolair® : Significantly stopped or reduced
oral corticosteroid (OCS) use
EXALT : Open-label study
63%
Patients in XOLAIR group were
able to reduce or stop OCS,
compared with 30% of patients
in the optimized asthma
therapy group, at week 32.
Siergiejko Z, et al. Oral corticosteroid sparing with omalizumab in severe allergic (igE-mediated) asthma 31
patients. Current Medical Research & Opinion 2011: 27: 2233-40
Xolair® : consistently improves overall Quality
of Life (QoL) across study
AQLQ score† Omalizumab
1.6 1.39
Control
**
1.4 1.19
***
1.2 1.12 1.02 1.01
0.94 0.93 *** ***
1.0 *** ***
0.8
0.61 0.64 0.61
0.6 0.49 0.46
*
0.4 0.26
0.18
0.2
0
INNOVATE ETOPA SOLAR Busse Solèr Holgate Pooled
study study study study study study
*p<0.05; **p<0.01; ***p<0.001 vs control
†Change from baseline (least squares mean). AQLQ = Asthma Quality of Life Questionnaire
33
Xolair® : Individualized Dosing
► Omalizumab is administered as a subcutaneous injection every 2
or 4 weeks based on patients’ bodyweight and baseline serum
IgE levels
Frequencies are defined as: Very common (≥1/10), common (>1/100; <1/10), uncommon (>1/1000;
<1/100), rare (<1/1000).
► Safety profile evaluated in more than 9,300 subject who treated with
Xolair® in clinical trial1
► Adverse events and laboratory profile for omalizumab were similar to
placebo/control
► > 400,000 patients had experience with Xolair® usage, since approved
in US in 2003 and in Europe in 20051
► Xolair® has been approved in > 90 countries worldwide1
► Evaluating Clinical Effectiveness and Long-term Safety in Patients with
Moderate to Severe Asthma (EXCELS) Study show no evidence of an
association between omalizumab use and an increased risk of
malignancy2
41
Summary
► Asthma is among the most prevalent chronic disease,
affecting 300 million people worldwide
► Approximately 70% asthma patients have allergies
► IgE plays a key role in allergic respiratory disease
* The anti-inflammatory effects of omalizumab provide proof of concept of the
importance of IgE in allergic respiratory disease