Coverage Policy Manual
Policy #: 2016003
Category: Pharmacy
Initiated: January 2016
Last Review: June 2022
  Omalizumab (e.g., Xolair)

Description:
Omalizumab, also known as rhuMAb-E25, is a chimeric monoclonal antibody specific for IgE and is used for the treatment of moderate to severe allergic asthma and chronic idiopathic urticaria.
 
In clinical trials, the addition of omalizumab to a patient’s drug regimen reduced the frequency of allergic asthma exacerbations compared to placebo, and more patients treated with omalizumab were able to reduce or discontinue the use of inhaled corticosteroids.
 
Chronic idiopathic urticaria (CIU), also known as chronic spontaneous urticaria, is defined as spontaneous hives and/or angioedema with no specific cause (other identifiable etiologies have been excluded) that persists for at least 6 weeks.
 
Chronic urticaria lesions typically have the following characteristics: edematous pink or red wheals of variable size and shape with surrounding erythema, generally pruritic, usually fade within 24-48 hours while new lesions may be developing spontaneously at other sites.
 
Some patients may have concurrent chronic urticaria and angioedema.  The history, review of systems, and physical examination are crucial in determining whether chronic urticaria is present or some other diagnosis should be considered.  When no underlying cause can be found chronic urticaria may be considered chronic idiopathic urticaria.  
 
Regulatory Status
 
Omalizumab was initially approved in 2003 by the U.S. Food and Drug Administration for the treatment of moderate to severe persistent asthma in patients (12 years of age and above) with a positive skin test or in vitro reactivity to a perennial aeroallergen and symptoms that are inadequately controlled with inhaled corticosteroids.
 
In September 2014, the U.S. Food and Drug Administration issued a safety announcement based on the review of safety studies. The review found a slightly higher rate of heart and brain blood vessels events in patients treated with Xolair compared to placebo. This information has been added to the drug label. Additionally, a potential for increased risk of cancer with Xolair has been added to the Warnings and Precautions section of the drug label.
 
In March 2014, the U.S. Food and Drug Administration approved the use of Omalizumab (e.g., Xolair) for the treatment of chronic idiopathic urticaria in adults and adolescents (12 years of age and above) who remain symptomatic despite H1 antihistamine treatment
 
In April 2021, the US Food and Drug Administration (FDA) approved the supplemental Biologics License Application for Omalizumab (e.g. Xolair) prefilled syringe for self-injection in appropriate patients across all approved US indications.

Policy/
Coverage:
PRIOR APPROVAL IS REQUIRED FOR OMALIZUMAB (e.g., XOLAIR)
 
Effective January 1, 2022, Omalizumab is not covered under the medical benefit. Please check the member’s pharmacy benefit for coverage. This policy applies to members whose plan utilizes AR BCBS pharmacy and has Omalizumab as a formulary option.
 
Effective February 2, 2022
 
  1. Asthma
  
Meets Primary Coverage Criteria Or Is Covered For Contracts Without Primary Coverage Criteria
 
The use of omalizumab meets member benefit certificate primary coverage criteria that there be scientific effectiveness as indicated for the treatment of adult patients that meet the criteria indicated below:
            
Initial 6-Month Trial
 
  1. The patient is 6 years of age or older (FDA, 2021); AND
  2. Documentation of diagnosis of moderate to severe persistent asthma (FDA, 2021)
  3. Documentation of inadequate control of symptoms with at least a 3-month history of compliance with a regular treatment regimen of optimal dosing of inhaled steroids (FDA, 2021) and a long-acting beta-agonist inhaler; AND
4. Sensitivity to a perennial aeroallergen by positive skin test or in-vitro IgE test (e.g., ImmunoCap test) must be demonstrated (FDA, 2021); AND
5. *For children 6 to <12 yrs of age, pre-treatment (with omalizumab) serum IgE must be between 30 and 1300 IU/ml and body weight no more than 150kg (FDA, 2021); AND
6. *For adults and adolescents 12 yrs and older, pre-treatment (with omalizumab) serum IgE must be between 30 and 700 IU/ml and body weight no more than 150kg (FDA, 2021); AND
7. **Evidence of asthma as demonstrated by both of the following:
      • A pretreatment forced expiratory volume in 1 second (FEV1) less than 80% predicted (FDA, 2021); AND
      • FEV1 reversibility of at least 12% and 200 milliliters (ml) after albuterol (salbutamol) administration (FDA, 2021).  
 
*Refer to dosing tables in FDA labeling
**FeNO testing is non-covered and is not considered adequate for establishing the diagnosis of asthma. Please see AR policy 2005020.
   
Subsequent Use (approval for 12 months)  
 
The use of omalizumab meets member benefit certificate primary coverage criteria that there be scientific effectiveness as indicated for the treatment of adult patients that meet the criteria indicated below:
 
  1. Clinical documentation in the medical records the demonstrates treatment with omalizumab resulted in improved health outcomes in at least one or more of the following:
      • Decreased use of at least 1 rescue medication; OR
      • Improved FEV1; OR
      • Decreased number of acute exacerbations.
 
Please refer to a separate policy on Site of Care or Site of Service Review (policy #2018030) for pharmacologic/biologic medications.
  
Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria
 
The use of omalizumab does not meet primary coverage criteria that there be scientific evidence of effectiveness for any other asthma related diagnosis other than what is listed above including:
      • acute asthma exacerbations
      • acute bronchospasm
      • status asthmaticus
      • nasal polyps
  
For members with contracts without primary coverage criteria, the use of omalizumab is investigational.  Investigational services are specific contract exclusions in most member benefit certificates of coverage.    
  
2. Chronic Idiopathic Urticaria
   
Meets Primary Coverage Criteria Or Is Covered For Contracts Without Primary Coverage Criteria
 
The use of Omalizumab meets member benefit certificate primary coverage criteria that there be scientific effectiveness as indicated for the treatment of chronic idiopathic urticaria for adults and adolescents when all the following criteria are met:
 
Initial 6 Month Approval
 
  1. The patient is 12 years of age or older (FDA, 2021); AND
  2. Other etiologies of urticaria have been excluded and there is no diagnosis of a more specific  etiology (e.g., allergic, contact, vibratory, thermal or cholinergic urticaria) (FDA, 2021); AND
  3. There must be a clear documentation of physical findings characteristic of chronic idiopathic urticaria (see above in “Description”) (FDA, 2021); AND  
  4. Dosing is in accordance with FDA guidance at 150 to 300 mg provided by subcutaneous injection every 4 weeks (FDA, 2021); AND  
5. There is documentation of failure of Step Therapy as outlined by the American Academy of Allergy, Asthma and Immunology in a 2014 update of guidelines for the diagnosis and management of acute and chronic urticaria.  Treatment should begin at the step appropriate for the patient’s level of symptom severity and previous treatment history.
 
Step therapy is as follows (American Academy of Allergy, Asthma, and Immunology, 2014):
Step 1: Monotherapy with second generation antihistamine
Step 2: One or more of the following as appropriate:
          • Dose advancement of 2nd generation antihistamine used in Step 1;
          • Add another 2nd generation antihistamine; AND/OR
          • Add H2 antagonist; AND/OR
              • Add leukotriene receptor antagonist; AND/OR
              • Add 1st generation antihistamine to be taken at bedtime.
Step 3: Dose advancement of potent antihistamines (eg hydroxyzine or doxepin) as tolerated.
Step 4: Add an alternative agent
            •  Omalizumab or cyclosporine OR
            •  Other anti-inflammatory agents, immunosuppressants, or biologics  
 
Subsequent Use (Reauthorization every 6 months)
 
The use of omalizumab meets member benefit certificate primary coverage criteria that there be scientific effectiveness as indicated for the treatment of chronic idiopathic urticaria (CIU) for subsequent use for  6 months provided there is documentation in the medical records of the following:
 
1. Documentation of clinical response (reduction in exacerbations, itch severity, hives); AND
2. Reauthorization every 6 months with documented need for continued approval   
3. After 2 years if there are no further outbreaks of CIU will documentation will support a trial off of omalizumab.
 
Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria
 
The use of omalizumab does not meet primary coverage criteria that there be scientific evidence of effectiveness for the treatment of other allergic conditions or other forms of urticaria.
 
For members with contracts without primary coverage criteria, the use of omalizumab is investigational. Investigational services are specific contract exclusions in most member benefit certificates of coverage.
 
Effective June 2021 TO February 1, 2022
 
  1. Asthma
  
Meets Primary Coverage Criteria Or Is Covered For Contracts Without Primary Coverage Criteria
 
The use of omalizumab (Xolair®) meets member benefit certificate primary coverage criteria that there be scientific effectiveness as indicated for the treatment of adult patients that meet the criteria indicated below:
            
Initial 6-Month Trial
 
  1. The patient is 6 years of age or older (FDA, 2021); AND
  2. Documentation of diagnosis of moderate to severe persistent asthma (FDA, 2021)
  3. Documentation of inadequate control of symptoms with at least a 3-month history of compliance with a regular treatment regimen of optimal dosing of inhaled steroids (FDA, 2021) and a long-acting beta-agonist inhaler; AND
4. Sensitivity to a perennial aeroallergen by positive skin test or in-vitro IgE test (e.g., ImmunoCap test) must be demonstrated (FDA, 2021); AND
5. *For children 6 to <12 yrs of age, pre-treatment (with omalizumab) serum IgE must be between 30 and 1300 IU/ml and body weight no more than 150kg (FDA, 2021); AND
6. *For adults and adolescents 12 yrs and older, pre-treatment (with omalizumab) serum IgE must be between 30 and 700 IU/ml and body weight no more than 150kg (FDA, 2021); AND
7. **Evidence of asthma as demonstrated by both of the following:
      • A pretreatment forced expiratory volume in 1 second (FEV1) less than 80% predicted (FDA, 2021); AND
      • FEV1 reversibility of at least 12% and 200 milliliters (ml) after albuterol (salbutamol) administration (FDA, 2021).  
 
*Refer to dosing tables in FDA labeling
**FeNO testing is non-covered and is not considered adequate for establishing the diagnosis of asthma. Please see AR policy 2005020.
   
Subsequent Use (approval for 12 months)  
 
The use of omalizumab (Xolair®) meets member benefit certificate primary coverage criteria that there be scientific effectiveness as indicated for the treatment of adult patients that meet the criteria indicated below:
 
  1. Clinical documentation in the medical records the demonstrates treatment with omalizumab resulted in improved health outcomes in at least one or more of the following:
      • Decreased use of at least 1 rescue medication; OR
      • Improved FEV1; OR
      • Decreased number of acute exacerbations.
 
Please refer to a separate policy on Site of Care or Site of Service Review (policy #2018030) for pharmacologic/biologic medications.
  
Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria
 
The use of omalizumab does not meet primary coverage criteria that there be scientific evidence of effectiveness for any other asthma related diagnosis other than what is listed above including:
      • acute asthma exacerbations
      • acute bronchospasm
      • status asthmaticus
      • nasal polyps
  
For members with contracts without primary coverage criteria, the use of omalizumab is investigational.  Investigational services are specific contract exclusions in most member benefit certificates of coverage.    
  
2. Chronic Idiopathic Urticaria
   
Meets Primary Coverage Criteria Or Is Covered For Contracts Without Primary Coverage Criteria
 
The use of Omalizumab meets member benefit certificate primary coverage criteria that there be scientific effectiveness as indicated for the treatment of chronic idiopathic urticaria for adults and adolescents when all the following criteria are met:
 
Initial 6 Month Approval
 
  1. The patient is 12 years of age or older (FDA, 2021); AND
  2. Other etiologies of urticaria have been excluded and there is no diagnosis of a more specific  etiology (e.g., allergic, contact, vibratory, thermal or cholinergic urticaria) (FDA, 2021); AND
  3. There must be a clear documentation of physical findings characteristic of chronic idiopathic urticaria (see above in “Description”) (FDA, 2021); AND  
  4. Dosing is in accordance with FDA guidance at 150 to 300 mg provided by subcutaneous injection every 4 weeks (FDA, 2021); AND  
5. There is documentation of failure of Step Therapy as outlined by the American Academy of Allergy, Asthma and Immunology in a 2014 update of guidelines for the diagnosis and management of acute and chronic urticaria.  Treatment should begin at the step appropriate for the patient’s level of symptom severity and previous treatment history.
 
Step therapy is as follows (American Academy of Allergy, Asthma, and Immunology, 2014):
Step 1: Monotherapy with second generation antihistamine
Step 2: One or more of the following as appropriate:
          • Dose advancement of 2nd generation antihistamine used in Step 1;
          • Add another 2nd generation antihistamine; AND/OR
          • Add H2 antagonist; AND/OR
              • Add leukotriene receptor antagonist; AND/OR
              • Add 1st generation antihistamine to be taken at bedtime.
Step 3: Dose advancement of potent antihistamines (eg hydroxyzine or doxepin) as tolerated.
Step 4: Add an alternative agent
            •  Omalizumab or cyclosporine OR
            •  Other anti-inflammatory agents, immunosuppressants, or biologics  
 
6. Due to risk of anaphylaxis with any dose, omalizumab must be administered in an office/facility that can manage such a reaction.  Only 150 mg of omalizumab may be administered at any one site so multiple injections may be necessary depending on  the dose administered (FDA, 2021).
  
Subsequent Use (Reauthorization every 6 months)
 
The use of omalizumab meets member benefit certificate primary coverage criteria that there be scientific effectiveness as indicated for the treatment of chronic idiopathic urticaria (CIU) for subsequent use for  6 months provided there is documentation in the medical records of the following:
 
1. Documentation of clinical response (reduction in exacerbations, itch severity, hives); AND
2. Reauthorization every 6 months with documented need for continued approval   
3. After 2 years if there are no further outbreaks of CIU will documentation will support a trial off of omalizumab.
 
Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria
 
The use of omalizumab does not meet primary coverage criteria that there be scientific evidence of effectiveness for the treatment of other allergic conditions or other forms of urticaria.
 
For members with contracts without primary coverage criteria, the use of omalizumab is investigational. Investigational services are specific contract exclusions in most member benefit certificates of coverage.
 
 
Effective March 2021  to May 2021
  1. Asthma
  
Meets Primary Coverage Criteria Or Is Covered For Contracts Without Primary Coverage Criteria
The use of omalizumab (Xolair®) meets member benefit certificate primary coverage criteria that there be scientific effectiveness as indicated for the treatment of adult patients that meet the criteria indicated below:
            
Initial 6-Month Trial
  1. The patient is 6 years of age or older; AND
  2. Documentation of diagnosis of moderate to severe persistent asthma
  3. Documentation of inadequate control of symptoms with at least a 3-month history of compliance with a regular treatment regimen of optimal dosing of inhaled steroids and a long-acting beta-agonist inhaler; AND
4. Sensitivity to a perennial aeroallergen by positive skin test or in-vitro IgE test (e.g., ImmunoCap test) must be demonstrated; AND
5. *For children 6 to <12 yrs of age, pre-treatment (with omalizumab) serum IgE must be between 30 and 1300 IU/ml and body weight no more than 150kg; AND
6. *For adults and adolescents 12 yrs and older, pre-treatment (with omalizumab) serum IgE must be between 30 and 700 IU/ml and body weight no more than 150kg; AND
7. **Evidence of asthma as demonstrated by both of the following:
      • A pretreatment forced expiratory volume in 1 second (FEV1) less than 80% predicted; AND
      • FEV1 reversibility of at least 12% and 200 milliliters (ml) after albuterol (salbutamol) administration.  
 *Refer to dosing tables in FDA labeling
 **FeNO testing is non-covered and is not considered adequate for establishing the diagnosis of
 asthma.    Please see AR policy 2005020
   
Subsequent Use (approval for 12 months)  
The use of omalizumab (Xolair®) meets member benefit certificate primary coverage criteria that there be scientific effectiveness as indicated for the treatment of adult patients that meet the criteria indicated below:
 
  1. Clinical documentation in the medical records the demonstrates treatment with omalizumab resulted in improved health outcomes in at least one or more of the following:
      • Decreased use of at least 1 rescue medication; OR
      • Improved FEV1; OR
      • Decreased number of acute exacerbations.
 
Please refer to a separate policy on Site of Care or Site of Service Review (policy #2018030) for pharmacologic/biologic medications.
  
Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria
The use of omalizumab does not meet primary coverage criteria that there be scientific evidence of effectiveness for any other asthma related diagnosis other than what is listed above including:
      • acute asthma exacerbations,
      • acute bronchospasm, or
      • status asthmaticus
  
For members with contracts without primary coverage criteria, the use of omalizumab is investigational.  Investigational services are specific contract exclusions in most member benefit certificates of coverage.    
  
2. Chronic Idiopathic Urticaria
   
Meets Primary Coverage Criteria Or Is Covered For Contracts Without Primary Coverage Criteria
The use of Omalizumab meets member benefit certificate primary coverage criteria that there be scientific effectiveness as indicated for the treatment of chronic idiopathic urticaria for adults and adolescents when all the following criteria are met:
 
Initial 6 Month Approval
  1. The patient is 12 years of age or older; AND
  2. Other etiologies of urticaria have been excluded and there is no diagnosis of a more specific  etiology (e.g., allergic, contact, vibratory, thermal or cholinergic urticaria); AND
  3. There must be a clear documentation of physical findings characteristic of chronic idiopathic urticaria (see above in “Description”); AND  
  4. Dosing is in accordance with FDA guidance at 150 to 300 mg provided by subcutaneous injection every 4 weeks; AND  
5. There is documentation of failure of Step Therapy as outlined by the American Academy of Allergy, Asthma and Immunology in a 2014 update of guidelines for the diagnosis and management of acute and chronic urticaria.  Treatment should begin at the step appropriate for the patient’s level of symptom severity and previous treatment history.
 
Step therapy is as follows:
Step 1: Monotherapy with second generation antihistamine
Step 2: One or more of the following as appropriate:
          • Dose advancement of 2nd generation antihistamine used in Step 1;
          • Add another 2nd generation antihistamine; AND/OR
          • Add H2 antagonist; AND/OR
              • Add leukotriene receptor antagonist; AND/OR
              • Add 1st generation antihistamine to be taken at bedtime.
Step 3: Dose advancement of potent antihistamines (eg hydroxyzine or doxepin) as tolerated.
Step 4: Add an alternative agent
            •  Omalizumab or cyclosporine OR
            •  Other anti-inflammatory agents, immunosuppressants, or biologics  
 
6. Due to risk of anaphylaxis with any dose, omalizumab must be administered in an office/facility that can manage such a reaction.  Only 150 mg of omalizumab may be administered at any one site so multiple injections may be necessary depending on  the dose administered.
  
Subsequent Use (Reauthorization every 6 months)
The use of omalizumab meets member benefit certificate primary coverage criteria that there be scientific effectiveness as indicated for the treatment of chronic idiopathic urticaria (CIU) for subsequent use for  6 months provided there is documentation in the medical records of the following:
 
1. Documentation of clinical response (reduction in exacerbations, itch severity, hives); AND
2. Reauthorization every 6 months with documented need for continued approval   
3. After 2 years if there are no further outbreaks of CIU will documentation will support a trial off of omalizumab.
 
Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria
The use of omalizumab does not meet primary coverage criteria that there be scientific evidence of effectiveness for the treatment of other allergic conditions or other forms of urticaria.
 
For members with contracts without primary coverage criteria, the use of omalizumab is investigational. Investigational services are specific contract exclusions in most member benefit certificates of coverage.     
 
Effective July 2019
 
Asthma
 
The following coverage statements address the use of omalizumab for the treatment of asthma.
 
Meets Primary Coverage Criteria Or Is Covered For Contracts Without Primary Coverage Criteria
 
I. Initial 6-Month Trial
 
Omalizumab meets member benefit contract Primary Coverage Criteria for effectiveness for members with moderate to severe persistent asthma for an initial 6-month trial period for patients who have demonstrated a proven reactivity to a perennial aeroallergen and the following criteria are met:
 
  1. The patient is 6 years of age or older; AND
  2. Documentation of inadequate control of symptoms with at least a 3-month history of compliance with a regular treatment regimen of optimal dosing of inhaled steroids and a long-acting beta-agonist inhaler; AND
  3. Sensitivity to a perennial aeroallergen by positive skin test or in-vitro IgE test (e.g., ImmunoCap test) must be demonstrated; AND
  4. *For children 6 to <12 yrs of age, pre-treatment (with omalizumab) serum IgE must be between 30 and 1300 IU/ml and body weight no more than 150kg; AND
  5. *For adults and adolescents 12 yrs and older, pre-treatment (with omalizumab) serum IgE must be between 30 and 700 IU/ml and body weight no more than 150kg; AND
  6. **Evidence of asthma as demonstrated by both of the following:
      • A pretreatment forced expiratory volume in 1 second (FEV1) less than 80% predicted; AND
      • FEV1 reversibility of at least 12% and 200 milliliters (ml) after albuterol (salbutamol) administration.  
 
*Refer to dosing tables in FDA labeling
 
**FeNO testing is non-covered and is not considered adequate for establishing the diagnosis of asthma.    Please see AR policy 2005020
 
Dosing and Administration
Dosing is in accordance with the FDA labeled dosing guidance; Administer Omalizumab 15 mg to 375 mg subQ every 2-4 weeks.  Determine dose and frequency by serum total IgE level (IU/mL) measured before the start of treatment, and by body weight.
 
II. Subsequent Use
 
For requests after the initial 6-month trial period, omalizumab meets member benefit contract Primary Coverage Criteria for effectiveness for members with moderate to severe persistent asthma for subsequent use for 1 year provided there is documentation in the medical records that treatment with omalizumab resulted in improved health outcomes in at least one or more of the following:
 
        1. Decreased use of at least 1 rescue medication; OR
        2. Improved FEV1; OR
        3. Decreased number of acute exacerbations.
 
Please refer to a separate policy on Site of Care or Site of Service Review (policy #2018030) for pharmacologic/biologic medications.
 
 
Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria
  
Any other use of omalizumab, including acute asthma exacerbations, acute bronchospasm, or status asthmaticus, does not meet Primary Coverage Criteria that there be scientific evidence of effectiveness.
 
For contracts without Primary Coverage Criteria, any other use of omalizumab is considered investigational and is not covered.
 
Investigational services are an exclusion in the member benefit certificate.
 
 
Chronic Idiopathic Urticaria
 
The following coverage statements address the use of omalizumab for the treatment of chronic idiopathic urticaria.
 
Meets Primary Coverage Criteria Or Is Covered For Contracts Without Primary Coverage Criteria
 
I. Initial 4-Month Trial
 
Omalizumab meets primary coverage criteria for the treatment of chronic idiopathic urticaria for adults and adolescents with refractory symptoms for an initial 4-month trial period when all of the following criteria are met:
 
A.  The patient is 12 years of age or older; AND
B. Other etiologies of urticaria have been excluded and there is no diagnosis of a more specific etiology (e.g., allergic, contact, vibratory, thermal or cholinergic urticaria); AND
C. There must be a clear documentation of physical findings characteristic of chronic idiopathic urticaria (see above in “Description”); AND
D.   Dosing is in accordance with FDA guidance at 150 to 300 mg provided by subcutaneous injection every 4 weeks; AND
E. There is documentation of failure of Step Therapy as outlined by the American Academy of Allergy, Asthma and Immunology in a 2014 update of guidelines for the diagnosis and management of acute and chronic urticaria.  Treatment should begin at the step appropriate for the patient’s level of symptom severity and previous treatment history. Step therapy is as follows:
 
Step 1: Monotherapy with second generation antihistamine
Step 2: One or more of the following as appropriate:
        • Dose advancement of 2nd generation antihistamine used in Step 1;
        • Add another 2nd generation antihistamine; AND/OR
        • Add H2 antagonist; AND/OR
            • Add leukotriene receptor antagonist; AND/OR
            • Add 1st generation antihistamine to be taken at bedtime.
Step 3: Dose advancement of potent antihistamines (eg hydroxyzine or doxepin) as tolerated.
Step 4: Add an alternative agent
        • Omalizumab or cyclosporine OR
        •  Other anti-inflammatory agents, immunosuppressants, or biologics  
 F. Due to risk of anaphylaxis with any dose, omalizumab must be administered in an office/facility that is capable of managing such a reaction.  Only 150 mg of omalizumab may be administered at any one site so multiple injections may be necessary depending on the dose administered.
 
II. Subsequent Use
 
For requests after the initial 4-month trial period, omalizumab meets member benefit certificate Primary Coverage Criteria for effectiveness for members with chronic idiopathic urticaria for subsequent use for 1 year provided there is documentation in the medical records of the following:
1. Documentation of improvement in physical symptoms; AND
2. Documentation in medical records of continued need for the treatment of omalizumab as evidenced by acute exacerbations following cessation of omalizumab following the initial 4-month trial.  
 
Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria
 
Omalizumab for the treatment of other allergic conditions or other forms of urticaria does not meet primary coverage criteria as there are no clinical trial results reporting safety and efficacy.
 
For contracts without Primary Coverage Criteria, omalizumab for the treatment of any other allergic condition or for urticaria other than chronic urticaria is considered investigational and is not covered.
 
Investigational services are an exclusion in the member benefit certificate.
 
 
Effective November 2018 to June 2019
 
Asthma
 
The following coverage statements address the use of omalizumab for the treatment of asthma.
 
Meets Primary Coverage Criteria Or Is Covered For Contracts Without Primary Coverage Criteria
 
I. Initial 6-Month Trial
 
Omalizumab meets member benefit contract Primary Coverage Criteria for effectiveness for members with moderate to severe persistent asthma for an initial 6-month trial period for patients who have demonstrated a proven reactivity to a perennial aeroallergen and the following criteria are met:
 
    1. The patient is 6 years of age or older; and
    2. Documentation of inadequate control of symptoms with at least a 3-month history of compliance with a regular treatment regimen of optimal dosing of inhaled steroids and a long-acting beta-agonist inhaler; and
    3. Sensitivity to a perennial aeroallergen by positive skin test or in-vitro IgE test (e.g., ImmunoCap test) must be demonstrated; and
    4. Pre-treatment (with omalizumab) serum IgE must be between 30 and 700 IU/ml; and
    5. Pre-treatment (with omalizumab) FEV1 less than 80%; and
    6. Dosing is in accordance with the FDA labeled dosing guidance;
 
II. Subsequent Use
 
For requests after the initial 6 month trial period, omalizumab meets member benefit contract Primary Coverage Criteria for effectiveness for members with moderate to severe persistent asthma for subsequent use for 1 year provided there is documentation in the medical records that treatment with omalizumab resulted in improved health outcomes in at least one or more of the following:
 
    1. Decreased use of at least 1 rescue medication; OR
    2. Improved FEV1; OR
    3. Decreased number of acute exacerbations.
 
 
Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria
  
Any other use of omalizumab, including acute asthma exacerbations, acute bronchospasm, or status asthmaticus, does not meet Primary Coverage Criteria that there be scientific evidence of effectiveness.
 
For contracts without Primary Coverage Criteria, any other use of omalizumab is considered investigational and is not covered. Investigational services are an exclusion in the member benefit certificate.
 
Chronic Idiopathic Urticaria
 
The following coverage statements address the use of omalizumab for the treatment of chronic idiopathic urticaria.
 
Meets Primary Coverage Criteria Or Is Covered For Contracts Without Primary Coverage Criteria
 
I. Initial 4-Month Trial
 
Omalizumab meets primary coverage criteria for the treatment of chronic idiopathic urticaria for adults and adolescents with refractory symptoms for an initial 4-month trial period when all of the following criteria are met:
 
A.  The patient is 12 years of age or older; AND
B. Other etiologies of urticaria have been excluded and there is no diagnosis of a more specific etiology (e.g., allergic, contact, vibratory, thermal or cholinergic urticaria); AND
C. There must be a clear documentation of physical findings characteristic of chronic idiopathic urticaria (see above in “Description”); AND
D.   Dosing is in accordance with FDA guidance at 150 to 300 mg provided by subcutaneous injection every 4 weeks; AND
E. There is documentation of failure of Step Therapy as outlined by the American Academy of Allergy, Asthma and Immunology in a 2014 update of guidelines for the diagnosis and management of acute and chronic urticaria.  Treatment should begin at the step appropriate for the patient’s level of symptom severity and previous treatment history. Step therapy is as follows:
 
Step 1: Monotherapy with second generation antihistamine
            Step 2  One or more of the following as appropriate:
            •  Dose advancement of 2nd generation antihistamine used in Step 1;
            •  Add another 2nd generation antihistamine; AND/OR
            •  Add H2 antagonist; AND/OR
            •  Add leukotriene receptor antagonist; AND/OR
            •  Add 1st generation antihistamine to be taken at bedtime.  
             Step 3  Dose advancement of potent antihistamines (eg hydroxyzine or doxepin) as tolerated.
             Step 4  Add an alternative agent
            •  Omalizumab or cyclosporine OR
            •  Other anti-inflammatory agents, immunosuppressants, or biologics  
 F. Due to risk of anaphylaxis with any dose, omalizumab must be administered in an office/facility that is capable of managing such a reaction.  Only 150 mg of omalizumab may be administered at any one site so multiple injections may be necessary depending on the dose administered.
 
II. Subsequent Use
 
For requests after the initial 4-month trial period, omalizumab meets member benefit certificate Primary Coverage Criteria for effectiveness for members with chronic idiopathic urticaria for subsequent use for 1 year provided there is documentation in the medical records of the following:
 
1. Documentation of improvement in physical symptoms; AND
2. Documentation in medical records of continued need for the treatment of omalizumab as evidenced by acute exacerbations following cessation of omalizumab following the initial 4-month trial.  
 
Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria
 
Omalizumab for the treatment of other allergic conditions or other forms of urticaria does not meet primary coverage criteria as there are no clinical trial results reporting safety and efficacy.
 
For contracts without Primary Coverage Criteria, omalizumab for the treatment of any other allergic condition or for urticaria other than chronic urticaria is considered investigational and is not covered. Investigational services are an exclusion in the member benefit certificate.
 
PRIOR APPROVAL IS REQUIRED FOR OMALIZUMAB (XOLAIR)
 
Asthma (Coverage Effective prior to November 2018)
 
The following coverage statements address the use of omalizumab for the treatment of asthma.
 
Meets Primary Coverage Criteria Or Is Covered For Contracts Without Primary Coverage Criteria
 
 I. Initial 6-Month Trial
 
Omalizumab meets member benefit contract Primary Coverage Criteria for effectiveness for members with moderate to severe persistent asthma for an initial 6-month trial period for patients who have demonstrated a proven reactivity to a perennial aeroallergen and the following criteria are met:
 
  1. The patient is 6 years of age or older; and
  2. Documentation of inadequate control of symptoms with at least a 3-month history of compliance with a regular treatment regimen of optimal dosing of inhaled steroids and a long-acting beta-agonist inhaler; and
  3. Sensitivity to a perennial aeroallergen by positive skin test or in-vitro IgE test (e.g., ImmunoCap test) must be demonstrated; and
  4. Pre-treatment (with omalizumab) serum IgE must be between 30 and 700 IU/ml; and
  5. Pre-treatment (with omalizumab) FEV1 less than 80%; and
  6. Dosing is in accordance with the FDA labeled dosing guidance; and  
  7. The patient is not an active cigarette smoker.
 
II. Subsequent Use
 
For requests after the initial 6 month trial period, omalizumab meets member benefit contract Primary Coverage Criteria for effectiveness for members with moderate to severe persistent asthma for subsequent use for 1 year provided there is documentation in the medical records that treatment with omalizumab resulted in improved health outcomes in at least one or more of the following:
 
            1. Decreased use of at least 1 rescue medication; OR
            2. Improved FEV1; OR
            3. Decreased number of acute exacerbations.
 
 
Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria
  
Any other use of omalizumab, including acute asthma exacerbations, acute bronchospasm, or status asthmaticus, does not meet Primary Coverage Criteria that there be scientific evidence of effectiveness.
 
For contracts without Primary Coverage Criteria, any other use of omalizumab is considered investigational and is not covered. Investigational services are an exclusion in the member benefit certificate.
 
 
Asthma (Coverage Effective Prior to 07/25/2016)
The following coverage statements address the use of omalizumab for the treatment of asthma.
 
Meets Primary Coverage Criteria Or Is Covered For Contracts Without Primary Coverage Criteria
 
I. Initial 6-Month Trial
 
Omalizumab meets member benefit contract Primary Coverage Criteria for effectiveness for members with moderate to severe persistent asthma for an initial 6-month trial period for patients who have demonstrated a proven reactivity to a perennial aeroallergen and the following criteria are met:
 
        1. The patient is 12 years of age or older; and
 
2. Documentation of inadequate control of symptoms with at least a 3-month history of compliance with a regular treatment regimen of optimal dosing of inhaled steroids and a long-acting beta-agonist inhaler; and
 
3. Sensitivity to a perennial aeroallergen by positive skin test or in-vitro IgE test (e.g., ImmunoCap test) must be demonstrated; and
 
4. Pre-treatment (with omalizumab) serum IgE must be between 30 and 700 IU/ml; and
 
5. Pre-treatment (with omalizumab) FEV1 less than 80%; and
 
6. Dosing is in accordance with the FDA labeled dosing guidance; and
 
7. The patient is not an active cigarette smoker.
 
II. Subsequent Use
 
For requests after the initial 6 month trial period, omalizumab meets member benefit contract Primary Coverage Criteria for effectiveness for members with moderate to severe persistent asthma for subsequent use for 1 year provided there is documentation in the medical records that treatment with omalizumab resulted in improved health outcomes in at least one or more of the following:
 
                    1. Decreased use of at least 1 rescue medication; OR
                    2. Improved FEV1; OR
                    3. Decreased number of acute exacerbations.
 
 
Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria
 
 
Any other use of omalizumab, including acute asthma exacerbations, acute bronchospasm, or status asthmaticus, does not meet Primary Coverage Criteria that there be scientific evidence of effectiveness.
 
For contracts without Primary Coverage Criteria, any other use of omalizumab is considered investigational and is not covered. Investigational services are an exclusion in the member benefit certificate.
 
 
Chronic Idiopathic Urticaria
 
The following coverage statements address the use of omalizumab for the treatment of chronic idiopathic urticaria.
 
Meets Primary Coverage Criteria Or Is Covered For Contracts Without Primary Coverage Criteria
 
I. Initial 4-Month Trial
 
Omalizumab meets primary coverage criteria for the treatment of chronic idiopathic urticaria for adults and adolescents with refractory symptoms for an initial 4-month trial period when all of the following criteria are met:
 
A.  The patient is 12 years of age or older; AND
 
B. Other etiologies of urticaria have been excluded and there is no diagnosis of a more specific etiology (e.g., allergic, contact, vibratory, thermal or cholinergic urticaria); AND
 
C. There must be a clear documentation of physical findings characteristic of chronic idiopathic urticaria (see above in “Description”); AND
 
D.   Dosing is in accordance with FDA guidance at 150 to 300 mg provided by subcutaneous injection every 4 weeks; AND
 
E. There is documentation of failure of Step Therapy as outlined by the American Academy of Allergy, Asthma and Immunology in a 2014 update of guidelines for the diagnosis and management of acute and chronic urticaria.  Treatment should begin at the step appropriate for the patient’s level of symptom severity and previous treatment history. Step therapy is as follows:
 
Step 1: Monotherapy with second generation antihistamine
 
             Step 2  One or more of the following as appropriate:
                •  Dose advancement of 2nd generation antihistamine used in Step 1;
                •  Add another 2nd generation antihistamine; AND/OR
                •  Add H2 antagonist; AND/OR
                •  Add leukotriene receptor antagonist; AND/OR
                •  Add 1st generation antihistamine to be taken at bedtime.  
 
            Step 3  Dose advancement of potent antihistamines (eg hydroxyzine or doxepin) as tolerated.
 
            Step 4  Add an alternative agent
                •  Omalizumab or cyclosporine OR
                •  Other anti-inflammatory agents, immunosuppressants, or biologics  
 
F. Due to risk of anaphylaxis with any dose, omalizumab must be administered in an office/facility that is capable of managing such a reaction.  Only 150 mg of omalizumab may be administered at any one site so multiple injections may be necessary depending on the dose administered.
 
II. Subsequent Use
For requests after the initial 4-month trial period, omalizumab meets member benefit certificate Primary Coverage Criteria for effectiveness for members with chronic idiopathic urticaria for subsequent use for 1 year provided there is documentation in the medical records of the following:
 
1. Documentation of improvement in physical symptoms; AND
2. Documentation in medical records of continued need for the treatment of omalizumab as evidenced by acute exacerbations following cessation of omalizumab following the initial 4-month trial.  
 
Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria
 
Omalizumab for the treatment of other allergic conditions or other forms of urticaria does not meet primary coverage criteria as there are no clinical trial results reporting safety and efficacy.
 
For contracts without Primary Coverage Criteria, omalizumab for the treatment of any other allergic condition or for urticaria other than chronic urticaria is considered investigational and is not covered. Investigational services are an exclusion in the member benefit certificate.

Rationale:
Chronic Idiopathic Urticaria
In 2013 the FDA approved omalizumab for the treatment of chronic idiopathic urticaria unresponsive to H1 antihistamines for adults and adolescents 12 years of age and older.  
 
The safety and efficacy of Xolair for the treatment of CIU was assessed in two placebo-controlled, multiple-dose clinical studies of 24 weeks’ duration (CIU Study 1; n= 319; Kaplan, 2013) and 12 weeks’ duration (CIU Study 2; n=322; Maurer, 2013). Patients received Xolair 75, 150, or 300 mg or placebo by SC injection every 4 weeks in addition to their baseline level of H1 antihistamine therapy for 24 or 12 weeks, followed by a 16-week washout observation period. A total of 640 patients (165 males, 475 females) were included for the efficacy analyses. Most patients were white (84%) and the median age was 42 years (range 12–72).
 
Disease severity was measured by a weekly urticaria activity score (UAS7, range 0–42), which is a composite of the weekly itch severity score (range 0–21) and the weekly hive 21 count score (range 0–21). All patients were required to have a UAS7 of 16, and a weekly itch severity score of 8 for the 7 days prior to randomization, despite having used an H1 antihistamine for at least 2 weeks. The mean weekly itch severity scores at baseline were fairly balanced across treatment groups and ranged between 13.7 and 14.5 despite use of an H1 antihistamine at an approved dose. The reported median durations of CIU at enrollment across treatment groups were between 2.5 and 3.9 years (with an overall subject-level range of 0.5 to 66.4 years).
 
In both CIU Studies 1 and 2, patients who received Xolair 150 mg or 300 mg had greater decreases from baseline in weekly itch severity scores and weekly hive count scores than placebo at Week 12. The 75-mg dose did not demonstrate consistent evidence of efficacy and is not approved for use.
 
Sussman et al (2014) published an article in reported a prospective open-label study of omalizumab, conducted in 2 different centers (Quebec n=34 – regular monthly injections; Toronto n=3 – on demand injections after positive response induced).  Sixty-one patients with chronic spontaneous urticaria, 6 with cold urticaria and 1 with urticarial vasculitis, a history of oral glucosteroid use and suboptimal response to previous treatments were included.  Fifty-six patients received 150 mg/dose while 11 patients received a higher dose.  Forty of forty-three patients who achieved remission were treated with 150 mg injections.  Patients in the Toronto subgroup were completely responsible for the costs of therapy while patients in the Quebec subgroup had therapy paid by private or public insurers.
 
The safety and effectiveness of Xolair for adolescent patients with CIU were evaluated in 39 patients 12 to 17 years of age (Xolair 29, placebo 10) included in three randomized, placebo-controlled CIU studies. A numerical decrease in weekly itch score was observed, and adverse reactions were similar to those reported in patients 18 years and older.
 
Clinical studies with Xolair have not been conducted in CIU patients below the age of 12 years. Considering the risk of anaphylaxis and malignancy seen in Xolair-treated patients 12 years old, the risk-benefit assessment does not support the use of Xolair in patients <12 years of age. Therefore, the use of Xolair in this patient population is not recommended.
 
Asthma
 
Based on the 2007 guidelines of the Expert Panel of the National Asthma Education and Prevention Program, omalizumab may be added to high-dose inhaled corticosteroids (ICSs) and long-acting beta-2 agonists (LABAs) in the treatment of inadequately controlled severe persistent asthma in adults and children 12 years of age and older who have relevant allergies (step 5 care) (National Asthma Education and Prevention Program Expert Panel 3, 2007). Omalizumab is under investigation for the treatment of seasonal and perennial allergic rhinitis, allergic dermatitis, and peanut allergy.  Omalizumab was approved by the FDA in June 2003 for use in patients with a positive skin test or in vitro reactivity to a perennial aeroallergen for the treatment of moderate to severe persistent asthma that is inadequately controlled despite the use of inhaled corticosteroids. The drug continues to be investigated in children < 12 years of age with allergic asthma. Although further study is needed, case reports indicate that omalizumab may be beneficial in treating children with refractory atopic dermatitis (Lane, 2006).
 
Busse and colleagues reported on a randomized, double-blind, controlled trial of 419 inner-city children, adolescents and young adults diagnosed with persistent asthma (Busse, 2011). Participants were randomized to either omalizumab or placebo. The primary outcome was asthma symptoms. Participants ranged in age from 6 to 20 years. The authors report, adding omalizumab compared to placebo, to guide-line directed therapy resulted in 1) a clinically significant decrease in asthma related symptoms; 2) a reduction in the number of participants with at least one exacerbation; 3) reduction in the number of hospitalizations; and 4) a reduced need for inhaled glucocorticoids to maintain the asthma control. The authors, however, “do not advocate its use outside of current recommendations”.  Additionally, omalizumab is not FDA approved for use in children less than 12 years of age.
 
2017 Update
A literature search conducted through June 2017 did not reveal any new information that would prompt a change in the coverage statement. The key identified literature is summarized below.
 
Odajima and colleagues published an uncontrolled extension study, in which treatment with omalizumab continued until the pediatric indication was approved in Japan (ClinicalTrials.gov number: NCT01328886).Thirty-eight Japanese children (aged 7-16 years) who completed the 24-week treatment core study were included. Thirty-five patients (92.1%) completed the extension study. The median exposure throughout the core and extension studies was 116.6 weeks (range, 46.9-151.1 weeks). The most common adverse events were nasopharyngitis, influenza, upper respiratory tract infection, and asthma. Serious adverse events developed in 10 patients (26.3%), but resolved completely with additional treatments. Incidence of adverse events didn't increase with extended exposure with omalizumab. Twenty-nine patients (76.3%) achieved completely- or well-controlled asthma compared with 9 patients (23.7%) at the start of the extension study. QOL scores, the rates (per year) of hospitalizations and ER visits were significantly improved compared with the baseline of the core study [39.0 vs 48.0 (median), p < 0.001 for QOL, 1.33 vs 0.16, p < 0.001 for hospitalization, 0.68 vs 0.15, p = 0.002 for ER visits]. Remarkably, the mean total IgE level showed a decreasing trend while exposure to omalizumab remained at steady-state.
 
2018 Update
A literature search conducted through June 2018 did not reveal any new information that would prompt a change in the coverage statement.
 
2019 Update
A literature search conducted through October 2019 did not reveal any new information that would prompt a change in the coverage statement.
 
2020 Update
A literature search conducted through September 2020 did not reveal any new information that would prompt a change in the coverage statement.
 
2022 Update
Annual policy review completed with a literature search using the MEDLINE database through June 2022. No new literature was identified that would prompt a change in the coverage statement.

CPT/HCPCS:
J2357Injection, omalizumab, 5 mg

References: Gevaert P, Omachi TA, Corren J, et al.(2020) Efficacy and safety of omalizumab in nasal polyposis: two randomized phase III trials. J Allergy and Clin Immunol. 2020; 146(3):595-605.

Li, JT, Oppenheimer, J, Bernstein, RA, et al.(2005) Attaining Optimal Asthma Control: A Practice Parameter. J Allergy and Clin Immunol. Oct 2005. doi:10.1016/j.jaci.2005.08.017.

Odajima H, Ebisawa M, Nagakura T, et al.(2017) Long-term safety, efficacy, pharmacokinetics and pharmacodynamics of omalizumab in children with severe uncontrolled asthma. Allergol Int. 2017 Jan;66(1):106-115.

U.S. Department of Health and Human Services.(2020) National Heart, Lung, and Blood Institute: 2020 Focused Updates to the Asthma Management Guidelines. NIH Publication No. 20-HL-8142. December 2020.

XOLAIR® (omalizumab)(2021) [package insert]. South San Francisco, CA, Genentech USA, Inc.; 2021


Group specific policy will supersede this policy when applicable. This policy does not apply to the Wal-Mart Associates Group Health Plan participants or to the Tyson Group Health Plan participants.
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