Indication and mechanism of Omalizumab in asthma, chronic rhino sinusitis with nasal polyp and chronic spontaneous urticaria

1. One Hit
3
Targets:The Role of Anti-IgE on
Chronic Urticaria,Asthma and Nasal Polyposis
Asst. Prof. Wannada Laisuan, MD.
Division of Allergy Immunology and Rheumatology,
Faculty of Medicine, Ramathibodi Hospital, Mahidol University

2. 2003 2014 2016 2020
FDA Approved omalizumab
Moderate-to-
Severe Asthma
Chronic
Idiopathic
Urticaria
Allergic Asthma
in Children > 6
years old
CRS with Nasal
Polyps
https://www.accessdata.fda.gov

3. Structural basis of omalizumab
Casale. WAO Journal 2008;174-183
Humbert M. Revue Des Maladies Respiratoires 22 (2005): 983-990
Bind to heavy-chain constant CH3 domain of IgE

4. Omalizumab and immunoglobulin E (IgE) complexes
✤ Soluble, inert immune
complexes
✤ Subsequently cleared by the
reticuloendothelial system
✤ Half-life 26 days
Brownell J, Casale TB.Immunol Allergy Clin North Am 2004;24:551-68

5. 2003 2014 2016 2020
FDA Approved omalizumab
Moderate-to-
Severe Asthma
Chronic
Idiopathic
Urticaria
Allergic Asthma
in Children > 6
years old
Adults with
Nasal Polyps
https://www.accessdata.fda.gov

7. FDA-Approved Omalizumab indication
Tyler SR. J Allergy Clin Immunol. 2019 Jul;144(1):13-23
Doroudchi A. Ann Allergy Asthma Immunol 124 (2020) 44-56
✤ Add-on therapy for patients > 6 yrs.
✤ Moderate-to-severe persistent asthma
inadequately controlled on ICS
✤ Total serum IgE level between 30 and
700 units/mL
✤ Positive allergen test

8. Mechanisms of Action of Omalizumab
Holgate ST. Nat Rev Immunol. 2008 Mar;8(3):218-30
Casale TB. J Allergy Clin Immunol. 1997;100(1):110e121
Omalizumab reduces free immunoglobulin E (IgE) by 96%

9. Omalizumab compared to standard of care for eosinophilic
asthma: A systematic review
Agache I. Allergy. 2020 May;75(5):1023-1042

10. Pooled data from two pivotal, phase III, double-blind, placebo-controlled registration trials of
omalizumab in moderate or severe allergic asthma
Response to Omalizumab using Patient Enrichment
Criteria from Trials of Novel Biologics in Asthma
Casale TB. Allergy. 2018 Feb;73(2):490-497

11. Effect of omalizumab on lung function and eosinophil levels in
adolescents with moderate-to-severe allergic asthma
Busse WW. Ann Allergy Asthma Immunol. 2020 Feb;124(2):190-196
Post hoc analysis, data from adolescents aged 12 to 17 years
8 randomized trials of omalizumab (studies 008, 009, and 011, and SOLAR, INNOVATE, ALTO, ETOPA, and EXTRA)
Omalizumab was associated with lung function improvements and circulating eosinophil
counts reductions in adolescents with moderate-to-severe uncontrolled asthma
Change from baseline in percent predicted (pp)
forced expiratory volume in 1 second (FEV1)
Eosinophil counts by least squares mean
(LSM) change from baseline

12. Omalizumab Effectiveness by Biomarker Status in Patients with
Asthma: Evidence From PROSPERO,A Prospective Real-World Study
Casale TB. J Allergy Clin Immunol Pract. 2019 Jan;7(1):156-164
806 allergic asthma patients, multicenter, prospective, 48-week effectiveness study of omalizumab conducted in the United States
Reduction of 81.9% in the percentage of
patients with 1 or more hospitalizations
A signi
fi
cant decrease in asthma
exacerbations (relative reduction 74%)

13. Omalizumab Effectiveness by Biomarker Status in Patients with
Asthma: Evidence From PROSPERO,A Prospective Real-World Study
Casale TB. J Allergy Clin Immunol Pract. 2019 Jan;7(1):156-164
806 allergic asthma patients, multicenter, prospective, 48-week effectiveness study of omalizumab conducted in the United States
Improvement in ACT score

14. Prospective, multicenter, randomized, parallel-group, double-blind, placebo-controlled trial
850 patients aged 12 to 75 years who had inadequately controlled asthma despite treatment with high-dose ICS plus LABAs, with or without other controllers
Omalizumab in Severe Allergic Asthma Inadequately
Controlled With Standard Therapy
25% relative reduction in the asthma exacerbation rate for patients who
received omalizumab compared with placebo (IRR, 0.75 [95% CI, 0.61 to 0.92])
Hanania NA. Ann Intern Med. 2011 May 3;154(9):573-82

15. Hanania NA. Am J Respir Crit Care Med. 2013 Apr 15;187(8):804-11.
Exploring the Effects of Omalizumab in Allergic Asthma
An Analysis of Biomarkers in the EXTRA Study
After 48 weeks of omalizumab, reductions in protocol-de
fi
ned exacerbations
were greater in high versus low sub- groups for all three biomarkers

16. Real-World Effectiveness of Omalizumab in Severe Allergic Asthma:
A Meta-Analysis of Observational Studies
✤ 77% patients achieved a good or excellent
GETE response after 16 weeks (RD: 0.77, 95%
CI: 0.70-0.84; P < .01, I2 = 96%)
✤ The effect continued with 82% of patients at 12
months (RD: 0.82, 95% CI: 0.73-0.91; P < .01),
with considerable heterogeneity (I2 = 97%)
Global evaluation of treatment effectiveness
Bousquet J. J Allergy Clin Immunol Pract. 2021 Jul;9(7):2702-2714

17. Omalizumab treatment reduced severe exacerbations in patients with severe allergic asthma
Real-World Effectiveness of Omalizumab in Severe Allergic Asthma:
A Meta-Analysis of Observational Studies
Bousquet J. J Allergy Clin Immunol Pract. 2021 Jul;9(7):2702-2714

18. 2003 2014 2016 2020
FDA Approved omalizumab
Moderate-to-
Severe Asthma
Chronic
Idiopathic
Urticaria
Allergic Asthma
in Children > 6
years old
Adults with
Nasal Polyps
https://www.accessdata.fda.gov

19. The EAACI/GA²LEN/EDF/WAO guideline for
chronic spontaneous urticaria (CSU)
Zuberbier T. Allergy 2018 Jul;73(7):1393-1414

20. Maurer M. Int Arch Allergy Immunol. 2020;181(5):321-333
Mechanism of CSU

21. Kaplan AP. Allergy. 2017 Apr;72(4):519-533
Mechanism of action of Omalizumab in CSU
Reduces activity of IgE autoantibodies against an autoantigen
Reduces activity of IgE
autoantibodies against an
autoantigen

22. Kaplan AP. Allergy. 2017 Apr;72(4):519-533
Mechanism of action of Omalizumab in CSU
Decrease expression of IgE receptors
(e.g. FceRI) and surface IgE and thus
lower levels of antigen available for IgG
autoantibody interaction
Reduces activity of IgG autoantibodies against FceRI and IgE

23. Reverse
basopenia
Improve IgE
receptor-mediated
histamine release
Reverses mechanism
that recruits basophils
to the skin
Maurer M. Int Arch Allergy Immunol. 2020;181(5):321-333
Kaplan AP. Allergy. 2017 Apr;72(4):519-533
Mechanism of action of Omalizumab in CSU
Basopenia
Reverses basopenia and
improves basophil IgE
receptor function

24. Similar Efficacy with Omalizumab in Chronic Idiopathic/
Spontaneous Urticaria Despite Different BackgroundTherapy
Casale TB. J Allergy Clin Immunol Pract. 2015 Sep-Oct;3(5):743-50

25. Similar Efficacy with Omalizumab in Chronic Idiopathic/
Spontaneous Urticaria Despite Different BackgroundTherapy
Casale TB. J Allergy Clin Immunol Pract. 2015 Sep-Oct;3(5):743-50
The proportions of patients with well- controlled symptoms (UAS7 < 6) and with complete symptom
control (UAS7 = 0) were signi
fi
cantly greater than placebo in each of the omalizumab groups

26. Similar Efficacy with Omalizumab in Chronic Idiopathic/
Spontaneous Urticaria Despite Different BackgroundTherapy
Casale TB. J Allergy Clin Immunol Pract. 2015 Sep-Oct;3(5):743-50

27. Hide M. J Dermatol Sci. 2017 Jul;87(1):70-78
POLARIS
Efficacy and safety of omalizumab in Japanese and Korean
patients with refractory chronic spontaneous urticaria
Mean change from baseline in ISS7 by study week Proportion of patients with UAS7 = 0 at Weeks
4, 8 and 12
Randomized, double-blind, placebo- controlled phase III trial of omalizumab for CSU in an Eastern Asian population

28. Omalizumab Re-Treatment and Step-Up in Patients with
Chronic Spontaneous Urticaria: OPTIMA Trial
Sussman G. J Allergy Clin Immunol Pract. 2020 Jul-Aug;8(7):2372-2378
Re-treatment with the 300 mg dose is accompanied by high rates of clinical improvement

29. The XTEND-CIU study: Long-term use of omalizumab in
chronic idiopathic urticaria
Maurer M. J Allergy Clin Immunol. 2018 Mar;141(3):1138-1139
Casale TB. J Am Acad Dermatol. 2018 Apr;78(4):793-795

30. The XTEND-CIU study: Long-term use of omalizumab in
chronic idiopathic urticaria
Primary ef
fi
cacy end point: Percentage of patients with CIU/CSU clinical worsening
Maurer M. J Allergy Clin Immunol. 2018 Mar;141(3):1138-1139

31. Omalizumab Updosing in Chronic Spontaneous Urticaria:
an Overview of Real-World Evidence
Proportion of patients with chronic spontaneous urticaria achieving complete or partial response
on updosing omalizumab from 300 to 450 or 600 mg every 4 weeks
Martin M.Clinical Reviews in Allergy & Immunology (2020) 59:38–45
Omalizumab updosing is associated with complete response rates in up to 60%
of patients with refractory CSU

32. Omalizumab Updosing in Chronic Spontaneous Urticaria:
an Overview of Real-World Evidence
Proportion of patients with chronic spontaneous urticaria achieving complete or partial response
on updosing omalizumab from 300 to 450 or 600 mg every 4 weeks
Martin M.Clinical Reviews in Allergy & Immunology (2020) 59:38–45
✤ Higher BMI
✤ Lower pre-omalizumab
urticarial control scores
✤ Lower IgE levels

33. Ef
fi
cacy and safety of treatment with omalizumab for chronic spontaneous
urticaria: A systematic review for the EAACI Biologicals Guidelines
Agache I. Allergy. 2021 Jan;76(1):59-70
Omalizumab 300 mg as add-on treatment signi
fi
cantly
reduces the signs and symptoms and burden of CSU

34. Decision making for the treatment of CSU with omalizumab
Türk M. J Allergy Clin Immunol Pract. 2020 Jan;8(1):113-124

35. 2003 2014 2016 2020
FDA Approved omalizumab
Moderate-to-
Severe Asthma
Chronic
Idiopathic
Urticaria
Allergic Asthma
in Children > 6
years old
Adults with
Nasal Polyps
https://www.accessdata.fda.gov

36. Thank you