Last Review Date: 10/03/2024

Date of Origin: 01/01/2012

Dates Reviewed: 06/2012, 02/2013, 04/2014, 09/2014, 07/2015, 07/2016, 09/2016, 12/2016, 03/2017, 06/2017, 09/2017, 12/2017, 03/2018, 06/2018, 10/2018, 10/2019, 10/2020, 12/2020, 01/2021, 05/2021, 08/2021, 10/2022, 10/2023, 03/2024, 04/2024, 10/2024

1. Length of Authorization

Coverage will be provided for 6 months and may be renewed annually, unless otherwise specified.

• Management of Immune Checkpoint Inhibitor-Related Toxicity: Coverage will be provided for 6 months and may NOT be renewed.

2. Dosing Limits

A. Quantity Limit (max daily dose) [NDC Unit]:

• Xolair 75 mg single-dose prefilled syringe/autoinjector: 1 syringe/autoinjector every 14 days
• Xolair 150 mg single-dose prefilled syringe/autoinjector: 4 syringes/autoinjectors every 14 days
• Xolair 150 mg single-dose vial for injection: 4 vials every 14 days
• Xolair 300 mg single-dose prefilled syringe/autoinjector: 2 syringes/autoinjectors every 14 days

B. Max Units (per dose and over time) [HCPCS Unit]:

   Allergic Asthma

• 75 billable units every 14 days

  CRSwNP and IgE-Mediated Food Allergy

• 120 billable units every 14 days

  All other indications

• 60 billable units every 28 days

3. Initial Approval Criteria ¹

Coverage is provided in the following conditions:

• Patient is at least 18 years of age (unless otherwise specified); AND

Universal Criteria ¹

• Will not be used in combination with another anti-IL4, anti-IL5 or IgG2 lambda monoclonal antibody agents (e.g., benralizumab, mepolizumab, reslizumab, dupilumab, tezepelumab etc.); AND

Moderate to Severe Persistent Allergic Asthma † ^1-3,20,25,29

• Patient is at least 6 years of age; AND
• Will not be used for treatment of acute bronchospasm, status asthmaticus, or allergic conditions (other than indicated); AND
• Patient has a positive skin test or in vitro reactivity to a perennial aero-allergen; AND
• Patient must weigh between 20 kg (44 lbs.) and 150 kg (330 lbs.); AND
• Patient has a serum total IgE level, measured before the start of treatment, of either:
  • ≥ 30 IU/mL and ≤ 700 IU/mL in patients age ≥ 12 years; OR
  • ≥ 30 IU/mL and ≤ 1300 IU/mL in patients age 6 to <12 years; AND
• Patient has documented ongoing symptoms of moderate-to-severe asthma* with a minimum (3) month trial on previous combination therapy including medium- or high-dose inhaled corticosteroids PLUS another controller medication (e.g., long-acting beta-2 agonist, leukotriene receptor antagonist, theophylline, etc.); AND
• Baseline measurement of at least one of the following for assessment of clinical status:
  • Use of systemic corticosteroids
  • Use of inhaled corticosteroids
  • Number of hospitalizations, ER visits, or unscheduled visits to healthcare provider due to condition
  • Forced expiratory volume in 1 second (FEV₁)

Chronic Idiopathic Urticaria/Chronic Spontaneous Urticaria (CIU/CSU) † ^1,4-6,8,28

• Patient is at least 12 years of age; AND
• The underlying cause of the patient’s condition is NOT considered to be any other allergic condition(s) or other form(s) of urticaria; AND
• Patient is avoiding triggers (e.g., NSAIDs, etc.); AND
• Documented baseline score from an objective clinical evaluation tool, such as: urticaria activity score (UAS7), angioedema activity score (AAS), Dermatology Life Quality Index (DLQI), Angioedema Quality of Life (AE-QoL), urticaria control test (UCT), angioedema control test (AECT), or Chronic Urticaria Quality of Life Questionnaire (CU-Q₂oL); AND
• Patient had an inadequate response to a one or more-month trial on previous therapy with scheduled dosing of a second-generation H1-antihistamine product**; AND

• Patient had an inadequate response to a one or more-month trial on previous therapy with scheduled dosing of at least one of the following:
  • Up-dosing/dose advancement (up to 4-fold) of a second generation H1-antihistamine**
  • Add-on therapy with a leukotriene antagonist (e.g., montelukast, zafirlukast, etc.)
  • Add-on therapy with another H1-antihistamine**
  • Add-on therapy with a H2-antagonist (e.g., ranitidine, famotidine, etc.)

Note: renewals will require a documented score from an objective clinical evaluation tool (e.g., UAS7, AAS, DLQI, AE-QoL, UCT, AECT, CU-Q₂oL, etc.) recorded within the previous 6 months.

Chronic Rhinosinusitis with Nasal Polyps (CRSwNP) † ^{1,22,23,26,27}

• Patient has bilateral symptomatic sino-nasal polyposis with symptoms lasting at least 12 weeks; AND
• Patient has failed at least 4 weeks of daily intranasal corticosteroid therapy; AND

• Patient has at least three (3) of the following indicators for biologic treatment:
  • Patient has evidence of type 2 inflammation (e.g., tissue eosinophils ≥10/hpf, blood eosinophils ≥ 150 cells/µL, or total IgE ≥ 100 IU/mL)
  • Patient has required ≥2 courses of systemic corticosteroids per year or >3 months of low dose corticosteroids, unless contraindicated
  • Disease significantly impairs the patient’s quality of life
  • Patient has experienced significant loss of smell
  • Patient has a comorbid diagnosis of asthma; AND
• Patient does not have any of the following:
  • • • • • • Antrochoanal polyps
            • Nasal septal deviation that would occlude at least one nostril
            • Disease with lack of signs of type 2 inflammation
            • Cystic fibrosis
            • Mucoceles; AND
• Other causes of nasal congestion/obstruction have been ruled out (e.g., acute sinusitis, nasal infection or upper respiratory infection, rhinitis medicamentosa, tumors, infections, granulomatosis, etc.); AND
• Physician has assessed baseline disease severity utilizing an objective measure/tool; AND

• Therapy will be used in combination with intranasal corticosteroids unless not able to tolerate or use is contraindicated

IgE-Mediated Food Allergic Reactions (Type 1) ^1,30,32

• Patient is at least 1 year of age; AND
• Patient is avoiding known food allergens; AND
• Patient has at least one IgE-mediated food allergy (i.e., peanut, milk, egg, wheat, or tree nuts); AND
• Patient’s allergy must be confirmed by at least one of the following***:

• Positive skin prick test (SPT)
  • Positive food specific serum IgE; AND

• Will not be used for the emergency treatment of allergic reactions, including anaphylaxis

***Note: If a positive diagnosis is unclear, an oral food challenge in addition to a strong history of an allergy, is recommended to confirm or exclude the presence of a food allergy.

Management of Immune Checkpoint Inhibitor-Related Toxicity ‡ ^9,10

• Patient has been receiving therapy with an immune checkpoint inhibitor (e.g., nivolumab, pembrolizumab, atezolizumab, avelumab, durvalumab, cemiplimab, ipilimumab, dostarlimab, tremelimumab, nivolumab/relatlimab, retifanlimab, tislelizumab, toripalimab, etc.); AND
• Patient has refractory and severe (i.e., grade 3: intense or widespread, constant, limiting self-care activities of daily living or sleep) pruritus; AND
• Patient has an increased serum IgE level above the upper limit of normal of the laboratory reference value; AND
• Patient has had no response to gabapentinoids (e.g., gabapentin, pregabalin) in 1 month

Systemic Mastocytosis ‡ ^9,11

• Used for the prevention of one of the following:

• Chronic mast cell mediator-related cardiovascular (e.g., pre-syncope, tachycardia, etc.) or pulmonary (e.g., wheezing, throat-swelling, etc.) symptoms insufficiently controlled by conventional therapy (e.g., H1 or H2 blockers or corticosteroids); OR
• Unprovoked anaphylaxis; OR
• Hymenoptera or food-induced anaphylaxis in patients with a negative test for specific IgE antibodies or a negative skin test; OR

• Used to improve tolerance while on immunotherapy (i.e., venom immunotherapy [VIT])

† FDA Approved Indication(s); ‡ Compendia Recommended Indication(s); Ф Orphan Drug

4. Renewal Criteria ¹

• Patient continues to meet the universal and other indication-specific relevant criteria identified in section III; AND
• Absence of unacceptable toxicity from the drug. Examples of unacceptable toxicity include: symptoms of anaphylaxis (bronchospasm, hypotension, syncope, urticaria, and/or angioedema), malignancy, symptoms similar to serum sickness (fever, arthralgia, and rash), parasitic (helminth) infection, eosinophilic conditions (e.g., vasculitic rash, worsening pulmonary symptoms, cardiac complications, and/or neuropathy, especially upon reduction of oral corticosteroids), etc.; AND

Moderate to Severe Persistent Allergic Asthma ^1-3,20,25

• Patient must weigh between 20 kg (44 lbs.) and 150 kg (330 lbs.); AND
• Improvement in asthma symptoms or asthma exacerbations as evidenced by decrease in one or more of the following:
  • • Use of systemic corticosteroids
    • Two-fold or greater decrease in inhaled corticosteroid use for at least 3 days
    • Hospitalizations
    • ER visits
    • Unscheduled visits to healthcare provider; OR
      • •  
• Improvement from baseline in forced expiratory volume in 1 second (FEV₁)

Chronic Idiopathic Urticaria/Chronic Spontaneous Urticaria (CIU/CSU) ^1,4-6,8,28

• Provider attests that the patient has been reassessed and continued therapy is necessary for the maintenance treatment of this condition; AND
• Treatment has resulted in clinical improvement as documented by improvement from baseline using objective clinical evaluation tools such as: the urticaria activity score (UAS7), angioedema activity score (AAS), Dermatology Life Quality Index (DLQI), Angioedema Quality of Life (AE-QoL), urticaria control test (UCT), angioedema control test (AECT), or Chronic Urticaria Quality of Life Questionnaire (CU-Q₂oL); AND
• Provider has current UAS7, AAS, DLQI, AE-QoL, UCT, AECT, or Cu-Q₂oL recorded within the past 6 months

Chronic Rhinosinusitis with Nasal Polyps (CRSwNP) ^{1,22,23,26,27}

• Disease response as indicated by improvement in signs and symptoms compared to baseline in one or more of the following: nasal/obstruction symptoms, improvement of sinus opacifications as assessed by CT-scans and/or an improvement on a disease activity scoring tool [e.g., nasal polyposis score (NPS), nasal congestion (NC) symptom severity score, sino-nasal outcome test-22 (SNOT-22), etc.]; OR
• Patient had an improvement in at least one (1) of the following response criteria:
  • • Reduction in nasal polyp size
    • Reduction in need for systemic corticosteroids
    • Improvement in quality of life
    • Improvement in sense of smell
    • Reduction of impact of comorbidities

IgE-Mediated Food Allergic Reactions (Type 1) ^1,30

• Provider attests that the patient has been reassessed and continued therapy is necessary for the maintenance treatment of this condition; AND
• Patient has had a reduction in allergic reaction, including anaphylaxis, and/or symptoms (e.g., moderate to severe skin, respiratory or gastrointestinal symptoms) associated with accidental exposure of known food allergens

Management of Immune Checkpoint Inhibitor-Related Toxicity ^9,10

• May not be renewed

Systemic Mastocytosis ^9,11

• Disease response as indicated by improvement in signs and symptoms compared to baseline or a decreased frequency of exacerbations

5. Dosage/Administration ^1,11-13

6. Billing Code/Availability Information

HCPCS Code:

• J2357 – Injection, omalizumab, 5 mg; 1 billable unit = 5 mg

NDC:

• Xolair 75 mg single-dose prefilled syringe or autoinjector: 50242-0214-xx
• Xolair 150 mg single-dose prefilled syringe or autoinjector: 50242-0215-xx
• Xolair 150 mg single-dose vial powder for injection: 50242-0040-xx
• Xolair 300 mg single-dose prefilled syringe or autoinjector: 50242-0227-xx

7. References

1. Xolair [package insert]. South San Francisco, CA; Genentech, Inc.; February 2024. Accessed August 2024.
2. National Asthma Education and Prevention Program (NAEPP). Guidelines for the diagnosis and management of asthma. Expert Panel Report 3. Bethesda, MD: National Institutes of Health (NIH), National Heart, Lung, and Blood Institute (NHLBI); August 2007.
3. Global Initiative for Asthma (GINA). Global Strategy for Asthma Management and Prevention. 2022 Update. Available from: https://ginasthma.org/wp-content/uploads/2022/07/GINA-Main-Report-2022-FINAL-22-07-01-WMS.pdf. Accessed September 2023.
4. Baiardini I, Braido F, Bindslev-Jensen C, et al. Recommendations for assessing patient-reported outcomes and health-related quality of life in patients with urticaria: a GA (2) LEN taskforce position paper. Allergy. 2011 Jul;66(7):840-4. doi: 10.1111/j.1398-9995.2011.02580.x. Epub 2011 Mar 9.
5. Zuberbier T, Aberer W, Asero R, et al. EAACI/GA²LEN/EDF/WAO guideline for the Definition, Classification, Diagnosis and Management of Urticaria. The 2017 Revision and Update. Allergy. 2018 Jan 15. doi: 10.1111/all.13397.
6. Maurer M, Rosén K, Hsieh HJ, et al. Omalizumab for the treatment of chronic idiopathic or spontaneous urticaria. N Engl J Med. 2013 Mar 7;368(10):924-35. doi: 10.1056/NEJMoa1215372. Epub 2013 Feb 24.
7. Siles RI, Hsieh FH. Allergy blood testing: A practical guide for clinicians. Cleve Clin J Med. 2011 Sep;78(9):585-92. doi: 10.3949/ccjm.78a.11023.
8. Bernstein JA, Lang DM, Khan DA, et al. The diagnosis and management of acute and chronic urticaria: 2014 update. J Allergy Clin Immunol. 2014 May;133(5):1270-7.
9. Referenced with permission from the NCCN Drugs and Biologics Compendium (NCCN Compendium^®) Omalizumab. National Comprehensive Cancer Network, 2024. The NCCN Compendium^® is a derivative work of the NCCN Guidelines^®. NATIONAL COMPREHENSIVE CANCER NETWORK^®, NCCN^®, and NCCN GUIDELINES^® are trademarks owned by the National Comprehensive Cancer Network, Inc. To view the most recent and complete version of the Compendium, go online to NCCN.org. Accessed August 2024.
10. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines^®) for Management of Immunotherapy-Related Toxicities 1.2024. National Comprehensive Cancer Network, 2024. NATIONAL COMPREHENSIVE CANCER NETWORK^®, NCCN^®, and NCCN GUIDELINES^® are trademarks owned by the National Comprehensive Cancer Network, Inc. To view the most recent and complete version of the Guidelines, go online to NCCN.org. Accessed August 2024.
11. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines^®) for Systemic Mastocytosis Version 3.2024. National Comprehensive Cancer Network, 2024. NATIONAL COMPREHENSIVE CANCER NETWORK^®, NCCN^®, and NCCN GUIDELINES^® are trademarks owned by the National Comprehensive Cancer Network, Inc. To view the most recent and complete version of the Guidelines, go online to NCCN.org. Accessed August 2024.
12. Carter MC, Robyn JA, Bressler PB, Walker JC, Shapiro GG, Metcalfe DD. Omalizumab for the treatment of unprovoked anaphylaxis in patients with systemic mastocytosis. J Allergy Clin Immunol. 2007;119(6):1550-1551.
13. Slapnicar C, Trinkaus M, Hicks L, Vadas P. Efficacy of Omalizumab in Indolent Systemic Mastocytosis. Case Rep Hematol. 2019;2019:3787586. Published 2019 Sep 16.
14. Jendoubi, F, Gaudenzio, N, Gallini, A, et al. Omalizumab in the treatment of adult patients with mastocytosis: A systematic review. Clin Exp Allergy. 2020; 50: 654– 661.
15. Busse W, Corren J, Lanier BQ, et al. Omalizumab, anti-IgE recombinant humanized monoclonal antibody, for the treatment of severe allergic asthma. J Allergy Clin Immunol. 2001;108(2):184-190.
16. Solèr M, Matz J, Townley R, et al. The anti-IgE antibody omalizumab reduces exacerbations and steroid requirement in allergic asthmatics. Eur Respir J. 2001;18(2):254-261.
17. Lanier B, Bridges T, Kulus M, et al. Omalizumab for the treatment of exacerbations in children with inadequately controlled allergic (IgE-mediated) asthma. J Allergy Clin Immunol. 2009;124(6):1210-1216.
18. Milgrom H, Berger W, Nayak A, et al. Treatment of childhood asthma with anti-immunoglobulin E antibody (omalizumab). Pediatrics. 2001;108(2):E36.
19. Saini SS, Bindslev-Jensen C, Maurer M, et al. Efficacy and safety of omalizumab in patients with chronic idiopathic/spontaneous urticaria who remain symptomatic on H1 antihistamines: a randomized, placebo-controlled study. J Invest Dermatol. 2015;135(1):67-75.
20. Holguin F, Cardet JC, Chung KF, et al. Management of severe asthma: a European

Respiratory Society/American Thoracic Society guideline. Eur Respir J 2020; 55: 1900588 [https://doi.org/10.1183/13993003.00588-2019].

21. Gevaert P, Omachi TA, Corren J, et al. Efficacy and safety of omalizumab in nasal polyposis: 2 randomized phase 3 trials. J Allergy Clin Immunol. 2020 Sep;146(3):595-605. doi: 10.1016/j.jaci.2020.05.032. Epub 2020 Jun 7.
22. Fokkens WJ, Lund V, Bachert C, et al. EUFOREA consensus on biologics for CRSwNP with or without asthma. Allergy. 2019;74(12):2312–2319. doi:10.1111/all.13875.
23. Gandhi NA, Bennett BL, Graham NMH, et al. Targeting key proximal drivers of type 2 inflammation in disease. Nat Rev Drug Discov. 2016;15(1):35-50.
24. ASCIA Chronic Spontaneous Urticaria (CSU) Position Paper and Treatment Guidelines; updated July 2020. Available at: https://www.allergy.org.au/hp/papers/chronic-spontaneous-urticaria-csu-guidelines.
25. National Asthma Education and Prevention Program (NAEPP). 2020 Focused Updates to the Asthma Management Guidelines: A Report from the National Asthma Education and Prevention Program Coordinating Committee Expert Panel Working Group. Bethesda, MD: National Institutes of Health (NIH), National Heart, Lung, and Blood Institute (NHLBI); December 2020.
26. Fokkens WJ, Viskens AS, Backer V, et. al. EPOS/EUFOREA update on indication and evaluation of Biologics in Chronic Rhinosinusitis with Nasal Polyps 2023. Rhinology 2023; 61:194.
27. Rank MA, Chu DK, Bognanni A, et al. The Joint Task Force on Practice Parameters GRADE guidelines for the medical management of chronic rhinosinusitis with nasal polyposis. J Allergy Clin Immunol 2023; 151:386.
28. Zuberbier T, Abdul Latiff AH, Abuzakouk M, et al. The international EAACI/GA²LEN/EuroGuiDerm/APAAACI guideline for the definition, classification, diagnosis, and management of urticaria. Allergy. 2022 Mar;77(3):734-766. doi: 10.1111/all.15090. Epub 2021 Oct 20.
29. Global Initiative for Asthma (GINA) Report: Global Strategy for Asthma Management and Prevention. 2023 Update. Available from: http://www.ginasthma.org/2023-gina-main-report. Accessed September 2023.
30. Wood RA, Chinthrajah RS, Rudman Spergel AK, et al; OUtMATCH study team. Protocol design and synopsis: Omalizumab as Monotherapy and as Adjunct Therapy to Multiallergen OIT in Children and Adults with Food Allergy (OUtMATCH). J Allergy Clin Immunol Glob. 2022 Jul 21;1(4):225-232. doi: 10.1016/j.jacig.2022.05.006. PMID: 37779534; PMCID: PMC10509974.
31. Muraro A, de Silva D, Halken S, et al. GA2LEN Food Allergy Guideline Group; GALEN Food Allergy Guideline Group. Managing food allergy: GA2LEN guideline 2022. World Allergy Organ J. 2022 Sep 7;15(9):100687. doi: 10.1016/j.waojou.2022.100687. PMID: 36119657; PMCID: PMC9467869.
32. Santos AF, Riggioni C, Agache I, et al. EAACI guidelines on the diagnosis of IgE-mediated food allergy. Allergy. 2023 Dec;78(12):3057-3076. doi: 10.1111/all.15902. Epub 2023 Oct 10. PMID: 37815205.
33. National Government Services, Inc. Local Coverage Article: Billing and Coding: Omalizumab (A52448). Centers for Medicare & Medicare Services. Updated on 03/04/2022 with effective dates 03/10/2022. Accessed August 2024.

Appendix 1 – Covered Diagnosis Codes

Appendix 2 – Centers for Medicare and Medicaid Services (CMS)

The preceding information is intended for non-Medicare coverage determinations. Medicare coverage for outpatient (Part B) drugs is outlined in the Medicare Benefit Policy Manual (Pub. 100-2), Chapter 15, §50 Drugs and Biologicals. In addition, National Coverage Determinations (NCDs) and/or Local Coverage Determinations (LCDs) may exist and compliance with these policies is required where applicable. Local Coverage Articles (LCAs) may also exist for claims payment purposes or to clarify benefit eligibility under Part B for drugs which may be self-administered. The following link may be used to search for NCD, LCD, or LCA documents: https://www.cms.gov/medicare-coverage-database/search.aspx. Additional indications, including any preceding information, may be applied at the discretion of the health plan.