BlueCross and BlueShield of Montana Medical Policy/Codes
Omalizumab (Xolair)
Chapter: Drugs - Medical Benefit
Current Effective Date: September 15, 2011
Original Effective Date: November 01, 2003
Publish Date: September 15, 2011
Revised Dates: April 11, 2007, September 15, 2011

On June 20, 2003 the Food and Drug Administration (FDA) approved Xolair (Omalizumab). The drug is the first recombinant humanized monoclonal anti-IgE antibody used to treat moderate-to-severe allergic asthma inadequately controlled by inhaled corticosteroids in patients 12 years and older.

Allergic asthma is a chronic, inflammatory disease of the airways triggered by exposure to airborne allergens. The allergic response relies on the immunoglobulin E (IgE) receptor found on a variety of cell types including basophils and mast cells. The inflammatory cascade begins with exposure to an allergen such as dust, pollen or mold which then binds with IgE to precipitate the release of inflammatory cell mediators. Xolair blocks this cascade by binding to circulating IgE which blocks both the immediate hypersensitivity response and chronic allergic inflammation.

Xolair was developed collaboratively by Genentech, Inc, Novartis Pharmaceuticals Corporation, and Tanox, Inc. It is given by subcutaneous injection once or twice a month. The use of Xolair in selected patients with allergic asthma is expected to decrease unscheduled outpatient visits, emergency room visits and hospitalizations due to exacerbation of their asthma. 


Prior authorization is recommended. To authorize, call the Blue Cross and Blue Shield of Montana (BCBSMT) Customer Service Department at 1-800-447-7828 or fax your request to the Medical Review Department at 406-437-7863. A retrospective review is performed if services are not prior authorized.

Medically Necessary

BCBSMT strongly recommends Xolair only be used under the supervision of an Allergist, Pulmonologist, or immunologist. BCBSMT considers the use of Xolair medically necessary when ALL of the following criteria are met:

  • Patient is age 12 or older;
  • Diagnosis of allergic asthma based on skin testing;
  • IgE level greater than or equal to 30 IU/ml and less than or equal to 700 IU/ml.
  • Clinical documentation that patient is compliant with high-dose inhaled corticosteroids and long-acting inhaled beta-2 agonists (Step 5 of the National Asthma Treatment Guidelines) and use of oral corticosteroids for exacerbation unless contraindicated.Evidence of reversible disease with treatment as demonstrated by at least:
  • Clinical documentation of poor asthma control or recurrent exacerbation requiring additional medication treatment:
    • Additional medical treatment may include any of the following: treatment with oral corticosteroids, ER visits, hospitalizations, or frequent office visits.
    • Poor asthma control may include (but is not limited to) clinical documentation of limitation of activities of daily living (ADLs), nighttime awakening, or dyspnea.
    • Recurrent exacerbation is defined as 2 or more acute exacerbations in a 12-month period.
  • Underlying conditions or triggers for asthma or pulmonary disease are being maximally managed.

Note: Omalizumab (Xolair) will, initially, be approved for 12 months. Ongoing use after inital approval will require submission of medical documentation to support evidence of efficacy and medical necessity for ongoing use.

    Not Medically Necessary

    BCBSMT considers the use of Xolair not medically necessary when used for the following conditions:

    • Allergic Rhinitis
    • Prevention of peanut or other food allergies 

    Advanced Member Notice of Financial Liability for Denied Services

    When the criteria for coverage is not met, BCBSMT encourages all participating providers to have a member complete and sign an Advanced Member Notification (AMN) form stating that BCBSMT will not cover this service, supply, device, or drug. If an AMN is signed prior to delivery of the service, participating providers can balance bill the patient. If an AMN is not signed, participating providers are financially liable and cannot balance bill the BCBSMT member for denied services. Services provided by an out-of-state provider that are denied as not medically necessary are the financial responsibility of the patient even if an AMN is signed.

    Refer to the Advanced Member Notification medical policy for more information. The AMN form is available at (Click on Providers and then Forms).


    BCBSMT considers the use of omalizumab investigational for all other conditions.

    Federal Mandate

    Federal mandate prohibits denial of any drug, device, or biological product fully approved by the FDA as investigational for the Federal Employee Program (FEP). In these instances coverage of these FDA-approved technologies are reviewed on the basis of medical necessity alone. Call the BCBSMT FEP Customer Service Department at 1-800-634-3569 for benefit information.



    Omalizumab is approved for adolescents (12 years and above) and adults with moderate-to-severe persistent asthma who have a positive skin test or in vitro reactivity to a perennial aeroallergen and whose symptoms are inadequately controlled with inhaled corticosteroids.

    Omalizumab is only covered under the medical benefit. Omalizumab is not considered a self-injectable medication due to product labeling indicating that medical observation for hypersensitivity reactions is necessary following administration.

    Omalizumab increases the number of patients who are able to reduce or withdraw their inhaled steroids and is effective in reducing asthma. [1, 2, 4, 7]

    Efficacy and dosing of omalizumab in patients with IgE levels greater than 700 have not been established. [24]

    The National Heart, Lung, and Blood Institute (NHLBI) defines asthma as a chronic inflammatory disorder of the airways in which many cells and cellular elements (multiple cytokines and mediators, as well as potentially IgE-mediated events involving mast cells and basophils) play a role (in particular, mast cells, eosinophils, T lymphocytes, macrophages, neutrophils and epithelial cells). IgE may be in the inflammatory cascade of some events leading to asthmatic airway inflammation, it is only one part of the picture.

    Efficacy and dosing of omalizumab in patients whose weight is outside the range provided in the standard dosing table for omalizumab has not been established (weight-IgE level combinations yielding doses greater than 750 mg every 4 weeks were excluded from clinical trials). [24, 25, 37]

    There are no available data demonstrating that omalizumab is superior to preferred options recommended in national treatment guidelines for moderate-to-severe persistent asthma. [14, 15, 20]

    Strict compliance with omalizumab is necessary because there is a 6 to 12 week lag before beneficial effects are apparent. (Effects are not immediate and explain the various phases that are included in study protocols.)

    Phase II results (suggesting benefits of another anti-IgE compound-TNX-901) cannot be extrapolated to the use of omalizumab to protect against anaphylaxis in patients with peanut allergy. [16]

    There are no published randomized controlled trials supporting the safety and efficacy of omalizumab (Xolair) in the treatment of chronic refractory autoimmune urticaria. Case reports, although are suggestive of benefit larger randomized control trials are needed to confirm these findings.

    Clinical Efficacy

    Omalizumab reduces seasonal and perennial allergic rhinitis symptoms, [3, 9, 22, 23] but has not been shown to have better efficacy than first-line alternatives (such as nasal corticosteroids, antihistamines, or allergen desensitization therapy). [13]

    The efficacy of omalizumab in patients with a history of smoking has not been established (patients with a smoking history in the previous two years or who had a previous history of greater than or equal to 10 pack-years were excluded from omalizumab clinical trials). [25]
    Total IgE Levels

    Omalizumab (Xolair) is dosed according to IgE levels between 30 to 700 IU/ml. There is no established dose or benefit for IgE levels outside of this range. There are studies that have included patients with IgE levels beyond 700 IU/ml. These trials were not designed to detect a difference between patients with lower IgE levels and those beyond the dosing recommendation in the manufacturer’s label. The majority of data on the use of omalizumab (Xolair) in patients with baseline IgE >700 IU/ml are limited to case reports with inconsistent results of effectiveness. IgE levels after administration of Xolair are relatively insignificant in trying to quantify because there are no labs to differentiate between bound and unbound (free) IGE.


    There is a black box warning for anaphylaxis.

    • Anaphylaxis in patients after treatment with omalizumab. These reactions generally occur within two hours of receiving omalizumab.
    • Delayed anaphylaxis—with onset two to 24 hours or even longer—after receiving omalizumab treatment.
    • Anaphylaxis can occur after any dose.
    • It is recommended that patients be observed for at least two hours after omalizumab is administered.
    • Urticaria is the most frequent adverse effect reported with short-term therapy. [12]

    There have been some initial concerns with elevated risks of cancer with omalizumab; however, an independent committee of oncologists reviewed available data and were unable to establish a direct correlation. [18, 19]

    The FDA is evaluating interim long-term safety data that suggest a risk of cardiovascular and cerebrovascular adverse events. [34]

    Rationale for Benefit Administration

    This medical policy was developed through consideration of peer reviewed medical literature, FDA approval status, accepted standards of medical practice in Montana, Technology Evaluation Center evaluations, and the concept of medical necessity. BCBSMT reserves the right to make exceptions to policy that benefit the member when advances in technology or new medical information become available.

    The purpose of medical policy is to guide coverage decisions and is not intended to influence treatment decisions. Providers are expected to make treatment decisions based on their medical judgment. Blue Cross and Blue Shield of Montana recognizes the rapidly changing nature of technological development and welcomes provider feedback on all medical policies.

    When using this policy to determine whether a service, supply, drug or device will be covered, please note tmember contract language will take precedence over medical policy when there is a conflict. 

    Procedural Codes: J2357
    1. Busse W et al. "Omalizumab, anti-IgE recombinant humanized monoclonal antibody, for the treatment of severe allergic asthma." J Allergy Clin Immunol 2001;108:184-90.
    2. Milgrom H et al. "Treatment of allergic asthma with monoclonal anti-IgE antibody." N Eng J Med 1999;341(26):1966-73.
    3. Adelroth E et al. "Recombinant humanized mAb-E25, an anti-IgEmab, in birch pollen induced seasonal allergic rhinitis." J Allergy Clin Immunol 2000;106(2):253-9.
    4. Soler M et al. "The anti-IgE antibody omalizumab reduces exacerbations and steroid requirement in allergic asthmatics." Eur Respir J 2001;18:254-61.
    5. Casale T et al. "Use of an anti-IgE humanized monoclonal antibody in ragweed-induced allergic rhinitis." J Allergy Clin Immunol 1997;100(1):110-21.
    6. Easthope S and Jarvis B. "Omalizumab." Drugs 2001;61(2):253-60.
    7. Milgrom H et al. "Treatment of childhood asthma with anti-immunoglobulin E antibody (omalizumab)." Pediatrics 2001;108(2):1-10.
    8. Chervinsky P et al. "Xolair® in the treatment of perennial allergic rhinitis (PAR)." J Allergy Clin Immunol 2001;107:S156.
    9. Kuehr J et al. "Efficacy of combination treatment with anti-IgE plus specific immunotherapy in polysensitized children and adolescents with seasonal allergic rhinitis." J Allergy Clin Immunol 2002;109:274-80.
    10. Holgate ST et al. "Omalizumab (Xolair, rhumab-E25), a novel therapy for severe allergic asthma [abstract]." Am J Respir Crit Care Med 2001;163(Suppl):A812.
    11. Holgate S et al. "Efficacy of omalizumab, an anti-immunoglobulin E antibody, in patients with allergic asthma at high risk of serious asthma-related morbidity and mortality." Curr Med Res Opin 2001;17:233-40.
    12. Berger W et al. "Long-term safety and tolerability of Xolair® - A double-blind, placebo-controlled study." Ann Allergy Asthma Immunol 2001;86:97.
    13. "The Allergy Report" American Academy of Allergy, Asthma and Immunology.© 2011 RegenceRx. All rights reserved. dru087.8 Page 7 of 8
    14. Guidelines for the Diagnosis and Management of Asthma," Expert Panel Report 2, Clinical Practice Guidelines, National Institutes of Health, National Heart Lung, and Blood Institute, NIH Publication 97-4051; July 1997.
    15. National Heart, Lung, and Blood Institute (NHLBI); National Asthma Education and Prevention Program: Expert Panel Report 3: Guidelines for the Diagnosis and Management of Asthma; 2007. Available at: accessed on 8/29/2007.
    16. Leung DYM et al. "Effect of anti-IgE therapy in patients with peanut allergy." New Eng J Med 2003;348:986-93.
    17. Corren J et al. "Omalizumab, a recombinant humanized anti-IgE antibody, reduces asthma-related emergency room visits and hospitalizations in patients with allergic asthma." J Allergy Clin Immunol 2003;111:87-90.
    18. Health Care Business Daily, May 15, 2003, FaxWatch, Inc.
    19. Health Care Business Daily, May 16, 2003, FaxWatch, Inc.
    20. Walker S et al. "Anti-IgE for chronic asthma (Cochrane Review)." In: The Cochrane Library, Issue 1, 2004. Chichester, UK: John Wiley & Sons, Ltd.
    21. Buhl R et al. "Omalizumab provides long-term control in patients with moderate-to-severe allergic asthma." Eur Respir J 2002;20:73-8.
    22. Chervinsky P et al. "Omalizumab, and anti-IgE antibody, in the treatment of adults and adolescents with perennial allergic rhinitis." Ann Allergy Asthma Immunol 2003;91:160-7.
    23. Casale TB et al. "Effect of omalizumab on symptoms of seasonal allergic rhinitis: a randomized controlled trial". J Am Med Assoc 2001;286(23)2956-67.
    24. Xolair® (omalizumab) prescribing information, Genentech, Inc; South San Francisco, CA, July 2010.
    25. Center for Drug Evaluation and Research. FDA Medical Officer’s Review of Omalizumab, BLA STN 103976/0. Available at:  
    26. Humbert M, Beasley R, Ayres J, Slavin R, Hebert J, Bousquet J, et al. Benefits of omalizumab as add-on therapy in patients with severe persistent asthma who are inadequately controlled despite best available therapy (GINA 2002 step 4 treatment): INNOVATE. Allergy. 2005;60:309-16.
    27. Walker S, Monteil M, Phelan K, Lasserson TJ,Walters EH. Anti-IgE for chronic asthma in adults and children. Cochrane Database of Systematic Reviews 2006, Issue 2. Art. No.: CD003559. DOI: 10.1002/14651858.CD003559.pub3.© 2011 RegenceRx. All rights reserved. dru087.8 Page 8 of 8
    28. FDA/Center for Drug Evaluation and Research: Safety Alert Healthcare Professional Information February 2007. Found at accessed June 13, 2007.
    29. Just J, Sahraoui F, Le Gros V, Grimfeld A. Effectiveness of omalizumab in monozygotic twin sisters with severe allergic asthma. Allergy. 2007 Apr;62(4):453-4..
    30. Okubo K, Ogino S, Nagakura T, Ishikawa T. Omalizumab is effective and safe in the treatment of Japanese cedar pollen-induced seasonal allergic rhinitis. Allergol Int. 2006 Dec;55(4):379-86.
    31. Cheng YX, Foster B, Holland SM, Klion AD, Nutman TB, Casale TB, Metcalfe DD, Prussin C. CD2 identifies a monocyte subpopulation with immunoglobulin E-dependent, high-level expression of Fc epsilon RI. Clin Exp Allergy. 2006 Nov;36(11):1436-45.
    32. Dewilde S, Turk F, Tambour M, Sandstrom T. The economic value of anti-IgE in severe persistent, IgE-mediated (allergic) asthma patients: adaptation of INNOVATE to Sweden. Curr Med Res Opin. 2006 Sep;22(9):1765-76.
    33. Noga O, Hanf G, Brachmann I, Klucken AC, Kleine-Tebbe J, Rosseau S, Kunkel G, Suttorp N, Seybold J. Effect of omalizumab treatment on peripheral eosinophil and T-lymphocyte function in patients with allergic asthma. J Allergy Clin Immunol. 2006 Jun;117(6):1493-9. Epub 2006 Apr 27.
    34. Early Communication about an Ongoing Sasfety Review of Omalizumab available at accessed July 17, 2009.
    35. From the Global Strategy for Asthma Management and Prevention, Global Initiative for Asthma (GINA) 2010. Available from: accessed May 25, 2011.
    36. Lowe PJ, Tannenbaum S, Gautier A, Jimenez P. Relationship between omalizumab pharmacokinetics, IgE pharmacodynamics and symptoms in patients with severe persistent allergic (IgE-mediated) asthma. Br J Clin Pharmacol. 2009 Jul; 68(1):61-76.
    37. Busse WW, Morgan WJ, Gergen PJ, Mitchell HE, Gern JE, Liu AH, Gruchalla RS, Kattan M, Teach SJ, Pongracic JA, Chmiel JF, Steinbach SF, Calatroni A, Togias A, Thompson KM, Szefler SJ, Sorkness CA. Randomized trial of omalizumab (anti-IgE) for asthma in inner-city children. N Engl J Med. 2011 Mar 17;364(11):1005-15.
     September 2011 Updated policy: Added rationale, references, and investigational statement. Medically Necessary and Not Medically Necessary statements unchanged. Coding remains the same.
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    Omalizumab (Xolair)