BENEFIT DESCRIPTION AND LIMITATIONS OF COVERAGE ITEM: PRODUCT LINES: COVERED UNDER: DESCRIPTION: CPT/HCPCS Code: Company Supplying: Setting: Xolair (omalizumab) Commercial HMO/PPO/CDHP HMO/PPO/CDHP: Rx Omalizumab is a recombinant humanized immunoglobulin G (IgG) 1 κ monoclonal antibody which selectively binds to human immunoglobulin E (IgE), thus inhibiting IgE from binding to the surface of mast cells and basophils (at the high-affinity IgE receptor [FcεRI]), and resulting in a decrease of mediators released in the allergic response. J2357 Genentech/Novartis self-administered Coverage Criteria: Express Scripts, Inc. monograph dated 03/03/2010 Approval Period: 12 months Black Box Warning: Anaphylaxis, presenting as bronchospasm, hypotension, syncope, urticaria, and/or angioedema of the throat or tongue, has been reported to occur after administration of omalizumab. Anaphylaxis has occurred as early as after the first dose of omalizumab but also has occurred beyond 1 year after beginning regularly administered treatment. Because of the risk of anaphylaxis, closely observe patients for an appropriate period of time after omalizumab administration and be prepared to manage anaphylaxis, which can be life-threatening. Also inform patients of the signs and symptoms of anaphylaxis and instruct them to seek immediate medical care if symptoms occur. Recommended Authorization Criteria Coverage of omalizumab is recommended in those who meet one of the following criteria: FDA-Approved Indications 1. Patients with moderate to severe persistent asthma must meet all (a, b, c, d, and e) of the following criteria (omalizumab is FDA-approved for the treatment of moderate to severe persistent asthma). a. Prescribed by or in consultation with an allergist, immunologist, or pulmonologist (The 2007 NAEPP guidelines state that referral to an asthma specialist for consultation or co-management is recommended if the patient is having difficulty achieving or maintaining control of asthma, if immunotherapy or omalizumab are considered, or if the patient has had an exacerbation requiring hospitalization.), and b. Baseline IgE level 30 IU/mL (Most of the clinical studies used this threshold for inclusion. Also, based on the mechanism of action of omalizumab in allergic asthma patients, who typically have higher than normal IgE levels, 1
and based on the dosing of omalizumab which requires an IgE level of 30 IU/mL or more to calculate a dose, this criterion has been adopted), and c. Patient has a positive skin test or in vitro testing (i.e., a blood test for allergen-specific IgE antibodies such as the radioallergosorbent test [RAST]) for one or more perennial aeroallergens (e.g., house dust mite [Dermatophagoides farinae, D. pteronyssinus], animal dander (dog, cat), cockroach, feathers, mold spores) (Omalizumab is FDA-approved for patients with moderate to severe persistent asthma who have a positive skin test or in vitro reactivity to a perennial aeroallergen), AND/OR for one or more seasonal aeroallergens (grass, pollen, weeds), and d. Patient s asthma symptoms have not been adequately controlled by inhaled corticosteroids (Omalizumab is FDA-approved for patients inadequately controlled with inhaled corticosteroids) AND a LABA (Inhaled corticosteroids plus a LABA are the recommended controller medications for asthma patients per the 2009 GINA guidelines and the 2007 NAEPP guidelines prior to the potential addition of omalizumab). If the patient has a contraindication or intolerance to use of LABAs, then one of the following agents are noted alternatives according to the GINA guidelines: sustained-release theophylline or leukotriene modifier (e.g., montelukast [Singulair ]). The patient must have been on concomitant therapy with an inhaled corticosteroid and a LABA (or listed alternative or collective use of LABA followed by a listed alternative(s)) for at least 3 months. [Note that the products Advair Diskus and HFA (fluticasone propionate and salmeterol inhalation powder) and Symbicort (budesonide and formoterol fumarate inhalation aerosol) contain both an inhaled corticosteroid and a LABA]. Inadequate control is demonstrated by: hospitalization for asthma (In the professional opinion of specialist physicians reviewing this data, we have adopted this criterion), or requirement for systemic (oral, parenteral) corticosteroids to control exacerbations of asthma (In the professional opinion of specialist physicians reviewing this data, we have adopted this criterion), or increasing need (usually > four times a day) for short-acting inhaled beta 2 agonists for symptoms (excluding preventive use for exerciseinduced asthma) (NAEPP and the GINA guidelines note this as a feature of uncontrolled asthma), and e. Patient is 12 years of age (Omalizumab is FDA-approved for use in patients aged 12 years and older). Other Uses with Supportive Evidence 2. Patients who are 6 and < 12 years of age and are currently stabilized on omalizumab for the treatment of asthma. Approve only if continuation of therapy. Omalizumab is FDA-approved for use in patients aged 12 years and older. However, a randomized, controlled study demonstrated some efficacy with omalizumab use in children down to the age of 6 years. 3. Patients with seasonal or perennial allergic rhinitis must meet all (a, b, c, d, e, f, and g) of the following criteria (Several controlled clinical studies have been performed assessing the efficacy of omalizumab in treating patients with seasonal or perennial allergic rhinitis): approve for 12 months. a. Prescribed by an allergist, immunologist, or pulmonologist (In the professional opinion of specialist physicians reviewing this data, we have adopted this criterion) and 2
b. Baseline IgE level 30 IU/mL (Most of the clinical studies used this threshold for inclusion. Also, based on the mechanism of action of omalizumab and the role that IgE plays in allergic rhinitis, this criterion has been adopted), and c. Patient has seasonal or perennial allergic rhinitis as demonstrated by positive skin testing (e.g., grass, tree, or weed pollen, mold spores, house dust mite, animal dander, cockroach) and/or positive in vitro testing (i.e., a blood test for allergen-specific IgE antibodies) for one or more relevant allergens (e.g., grass, tree, or weed pollen, mold spores, house dust mite, animal dander, cockroach) The 2008 practice parameter for management of rhinitis notes that determination of specific IgE by skin testing or in vitro testing is indicated to provide evidence of an allergic basis for the patient s symptoms, confirm suspected causes of the patient s symptoms, or assess the sensitivity to a specific allergen for avoidance measures and/or allergen immunotherapy. (In the professional opinion of specialist physicians reviewing this data, we have adopted this criterion), and d. Patient has tried therapy with at least one drug from 2 of the following groups of drugs at the same time i) A non-sedating or low-sedating antihistamine (e.g., fexofenadine [generics, Allegra ], loratadine [generics, Claritin ] (Rx or OTC), desloratadine [Clarinex ], levocetirizine [Xyzal], or cetirizine [generics, Zyrtec ] (Rx or OTC) or their combination with pseudoephedrine) OR a nasal antihistamine (i.e., azelastine [Astelin, Astepro] or olopatadine [Patanase]), ii) A nasal corticosteroid (e.g., beclomethasone (Beconase AQ ), fluticasone (generics, Flonase )) iii) montelukast (Singulair). Examples are: fexofenadine plus a nasal corticosteroid or desloratadine plus montelukast. OR Patient must have tried therapy with at least one drug from all 3 of the above groups individually or in any combination during one allergy season (i.e., 6 months) (In the professional opinion of specialist physicians reviewing this data, we have adopted this criterion), and e. Patient has had immunotherapy, is receiving immunotherapy, or will be receiving immunotherapy. A double-blind, placebo-controlled study involving 159 patients found that use of omalizumab for 9 weeks prior to rush immunotherapy (RIT) resulted in a lower rate of any systemic or other adverse reaction on the day of RIT, including a statistically significant reduction in the incidence of anaphylaxis (5.6% for omalizumab plus RIT vs. 25.6% for placebo plus RIT; P = 0.026). Exceptions can be made for patients when there is no immunotherapy available for the allergen identified as causing clinically significant allergy or there are contraindications to immunotherapy. Well-controlled clinical studies have demonstrated that allergen immunotherapy is beneficial in allergic rhinitis caused by: tree pollens (e.g., birch, mountain cedar), grass pollens (e.g., timothy, rye), weed pollens (e.g., ragweed), mold spores (e.g., Alternaria, Cladosporium spp), dust mites (e.g., D. farinae, D. pteronyssinus), and animal dander (e.g., cat). Immunotherapy usually is given for at least 3 to 5 years and longer in some. The following patients should not receive immunotherapy: patients on beta blockers and patients with medical conditions that reduce their ability to survive a systemic allergic reaction (e.g., markedly compromised lung function, poorly controlled asthma, unstable angina, recent myocardial infarction or significant dysrhythmia, uncontrolled hypertension, failure of a major organ system such as renal failure). The major risk in patients with allergic rhinitis receiving immunotherapy is anaphylaxis (In the professional 3
opinion of specialist physicians reviewing this data, we have adopted this criterion). f. If the patient has allergies to animals (e.g., cats, dogs), these animals have been removed from the patient s immediate environment (e.g., work, home) (In the professional opinion of specialist physicians reviewing this data, we have adopted this criterion). g. Patient is 12 years of age (Adequate controlled clinical studies have included patients aged 12 years and older). Note: Some patients with asthma also have allergic rhinitis. 4. Patients with eosinophilic gastroenteritis (EG), eosinophilic esophagitis (EE), or eosinophilic colitis must meet all (a, b, c, and d) of the following criteria. In a case series omalizumab was effective in decreasing absolute eosinophil count, allergen skin test wheal and erythema responses, and symptom scores. a) Prescribed by or in consultation with an allergist, immunologist, or gastroenterologist (In the professional opinion of specialist physicians reviewing this data, we have adopted this criterion), and b) Patient has tried therapy with a systemic or orally administered topical corticosteroid. It is recognized that corticosteroids (systemic or topical administered by swallowing a formulation for inhalation) are the standard treatment for management of both EG and EE. c) Diagnosis has been confirmed based on biopsy showing 15 eosinophils per high-power field (In the professional opinion of specialist physicians reviewing this data, we have adopted this criterion). d) Patient is 12 years of age. (Adequate controlled clinical studies have not been conducted in patients less than 12 years of age with EG, EE, or eosinophilic colitis.) Dosing: Pretreatment serum IgE (units/ml) Omalizumab Doses Administered Every 4 Weeks (mg) Body weight (kg) 30 to 60 > 60 to 70 > 70 to 90 > 90 to 150 30 to 100 150 150 150 300 > 100 to 200 300 300 300 See the following > 200 to 300 300 See the following Pretreatment serum IgE (units/ml) > 100 to 200 See previous > 200 to 300 See previous See the following Omalizumab Doses Administered Every 2 Weeks (mg) Body weight (kg) See the following 30 to 60 > 60 to 70 > 70 to 90 > 90 to 150 See previous See previous 225 225 225 300 > 300 to 400 225 225 300 Do not dose. > 400 to 500 300 300 375 Do not dose. > 500 to 600 300 375 Do not dose. Do not dose. > 600 to 700 375 Do not dose. Do not dose. Do not dose. 4
Exclusions Coverage of omalizumab is not recommended in the following circumstances: 1. For treatment of peanut allergy. A Phase II multicenter clinical trial was recently initiated using omalizumab in patients with peanut allergy; however, it had to be discontinued prematurely due to concerns with the safety of the oral peanut challenges in some study subjects. Insufficient data were obtained to reach any conclusions about the efficacy of omalizumab despite a slight trend towards greater peanut tolerability with omalizumab compared with placebo. 2. For the treatment of latex allergy in health care workers with occupational latex allergy. A small (European) study assessed the effects of omalizumab use on treating health care workers (n = 18) with occupational latex allergy. Omalizumab use in these patients resulted in a reduction in mean conjunctival challenge test scores as compared to placebo-treated patients after 16-weeks of therapy. Also, three patients who did not respond to omalizumab treatment during the double-blind phase, responded during the 16-week open-label phase, thus the overall ocular response rate for all patients in the open-label phase was 93.8% (15/16). Also 11 of 15 patients in the open-label phase had a negative response to a latex glove challenge test (4 had a mild response). 3. For the treatment of atopic dermatitis (AD). Three different case series reports have reported inconsistent results for use of omalizumab in patients (adults and children) with AD. Two of these case series directly assessed the use of omalizumab for treating AD, while the third study was using omalizumab for managing persistent asthma in patients with concomitant AD. Well-controlled clinical trials are needed to determine if omalizumab has a role in the treatment of AD. 4. For use in patients < 12 years of age. Omalizumab is not FDA-approved for use in patients under 12 years of age. Adequate controlled clinical studies in patients < 12 years of age with a diagnosis of seasonal or perennial allergic rhinitis, eosinophilic gastroenteritis, eosinophilic esophagitis, or eosinophilic colitis have not been performed. Considering the risk of anaphylaxis and malignancy seen in omalizumab-treated patients with asthma who were 12 years old and the modest efficacy of omalizumab in the pivotal pediatric study, the risk-benefit assessment does not support the use of omalizumab in patients younger than 12 years of age. Exceptions may be made for patients who are 6 and < 12 years of age and are stabilized on omalizumab. See criteria #2. Coverage is not recommended for circumstances not listed in the Recommended Authorization Criteria. Criteria will be updated as new published data are available. APPROVAL: ENDORSED BY: Pharmacy & Therapeutics Committee Original Date: APPROVED BY: Date: 7/21/2010 5