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Xolair (omalizumab) - 4 indications
- for the treatment of moderate to severe persistent asthma in adults and children at least 6 years of age; approved June of 2003
- for the treatment of chronic idiopathic urticaria in adults and children at least 12 years of age; approved March 2014
- for nasal polyps in adult patients 18 years of age and older; approved December of 2020
- for children and adults with one or more food allergies; approved February of 2024
General Information
Xolair is a recombinant DNA-derived humanized IgG1k monoclonal antibody that selectively binds to human immunoglobulin E (IgE). This limits the degree of release of mediators of the allergic response.
Xolair is specifically indicated for the following:
- adults and children (6 years of age and above) 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;
- chronic idiopathic urticaria in adults and adolescents 12 years of age and older who remain symptomatic despite H1 antihistamine treatment;
- nasal polyps in adult patients 18 years of age and older with inadequate response to nasal corticosteroids, as add-on maintenance treatment;
- IgE-mediated food allergy in adult and pediatric patients aged 1 year and older for the reduction of allergic reactions (Type I), including anaphylaxis, that may occur with accidental exposure to one or more foods. To be used in conjunction with food allergen avoidance.
Xolair is supplied as a powder for reconstitution into a solution for subcutaneous injection. Scroll down for the recommended dosing for each indication.
Xolair is also supplied as a prefilled syringe for self-injection for all indications. Before starting self-injection with Xolair prefilled syringe, the patient must have no prior history of anaphylaxis and be closely observed by a healthcare provider for at least three injections with no hypersensitivity.
Mechanism of Action
Asthma, Chronic Rhinosinusitis with Nasal Polyps, and IgE-Mediated Food Allergy:
Omalizumab inhibits the binding of IgE to the high-affinity IgE receptor on the surface of mast cells, basophils, and dendritic cells, resulting in high-affinity IgE receptor down-regulation on these cells.
In allergic asthmatics, treatment with omalizumab inhibits IgE-mediated inflammation, as evidenced by reduced blood and tissue eosinophils and reduced inflammatory mediators, including IL-4, IL-5, and IL-13.
Chronic Spontaneous Urticaria
Omalizumab binds to IgE and lowers free IgE levels. Subsequently, IgE receptors on cells down-regulate. The mechanism by which these effects of omalizumab result in an improvement of chronic spontaneous urticaria (CSU) symptoms is unknown.
Side Effects
Adverse events associated with the use of Xolair may include, but are not limited to, the following:
- Injection site reaction
- Viral infections
- Upper respiratory tract infection
- Sinusitis
- Headache
- Pharyngitis
The Xolair drug label comes with the following 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 Xolair. Anaphylaxis has occurred after the first dose of Xolair but also has occurred beyond 1 year after beginning treatment. Initiate Xolair therapy in a healthcare setting, closely observe patients for an appropriate period of time after Xolair administration and be prepared to manage anaphylaxis which can be life threatening. Inform patients of the signs and symptoms of anaphylaxis and have them seek immediate medical care should symptoms occur. Selection of patients for self-administration of Xolair should be based on criteria to mitigate risk from anaphylaxis.
Indication 1 - for the treatment of moderate to severe persistent asthma in adults and children at least 6 years of age
approved June 2003
Xolair 75 to 375 mg SC every 2 or 4 weeks. Determine dose (mg) and dosing frequency by serum total IgE level (IU/mL), measured before the start of treatment, and body weight (kg). See the dose determination charts.
The FDA approval of Xolair for asthma was based on three randomized, double-blind, placebo-controlled, multicenter trials. The trials enrolled patients 12 to 76 years old, with moderate to severe persistent asthma for at least one year, and a positive skin test reaction to a perennial aeroallergen.
Studies One and Two
At screening, patients in Studies 1 and 2 had a forced expiratory volume in one second (FEV1) between 40% and 80% predicted. All subjects were being treated with inhaled corticosteroids (ICS) and short acting beta-agonists. The studies were comprised of a run-in period to achieve a stable conversion to a common ICS (beclomethasone dipropionate) followed by randomization to Xolair or placebo. Xolair was administered for 16 weeks with an unchanged corticosteroid dose unless an acute exacerbation necessitated an increase (referred to as the stable steroid phase). The subjects then entered an ICS reduction phase of 12 weeks during which ICS dose reduction was attempted in a step-wise manner (referred to as the Steroid Reduction Phase). The subjects were treated according to a dosing table to administer at least 0.016 mg/kg/IU (IgE/mL) of Xolair or a matching volume of placebo over each 4-week period. The maximum Xolair dose per 4 weeks was 750 mg. Those who were to receive more than 300 mg within the 4-week period were administered half the total dose every 2 weeks. In both Studies 1 and 2 the number of exacerbations per patient was reduced in patients treated with Xolair compared with placebo.
Stable Steroid Phase Study One: Mean number exacerbations/patient was 0.2% for Xolair and and 0.3% for placebo (p- 0.005). Study Two: Mean number exacerbations/patient was 0.1% for Xolair and 0.4% for placebo (p< 0.001).
Steroid Reduction Phase Study Two: Mean number exacerbations/patient was 0.2% for Xolair and 0.4% for placebo (p- 0.004). Study Two: Mean number exacerbations/patient was 0.2% and 0.3% (p< 0.001). Improvements in measures of airflow (FEV1) and asthma symptoms were also observed.
Study Three
In Study 3 there was no restriction on screening FEV1. Long-acting beta-agonists were allowed and subjects were receiving at least 1000 µg/day fluticasone propionate; a subset was also receiving oral corticosteroids. The studies were comprised of a run-in period to achieve a stable conversion to a common ICS (fluticasone propionate) followed by randomization to Xolair or placebo. Subjects were stratified by use of ICS-only or ICS with concomitant use of oral steroids. Xolair was administered for 16 weeks with an unchanged corticosteroid dose unless an acute exacerbation necessitated an increase (referred to as the stable steroid phase). The subjects then entered an ICS reduction phase of 16 weeks during which ICS (or oral steroid in Study 3 subset) dose reduction was attempted in a step-wise manner (referred to as the Steroid Reduction Phase). The subjects were treated according to a dosing table to administer at least 0.016 mg/kg/IU (IgE/mL) of Xolair or a matching volume of placebo over each 4-week period. The maximum Xolair dose per 4 weeks was 750 mg. Those who were to receive more than 300 mg within the 4-week period were administered half the total dose every 2 weeks. In Study 3 the number of exacerbations in patients treated with Xolair was similar to that in placebo-treated patients. The absence of an observed treatment effect was postulated to be related to differences in the patient population.
Stable Steroid Phase Inhaled Only: % Patients with ≥ 1 exacerbations was 15.9% for Xolair and 15.0% for placebo. Oral plus Inhaled: % Patients with ≥ 1 exacerbations was 32.0% for Xolair and 22.2% for placebo.
Steroid Reduction Phase Inhaled Only: % Patients with ≥ 1 exacerbations was 22.2% for Xolair and 26.7% for placebo. Oral plus Inhaled: % Patients with ≥ 1 exacerbations was 42.0% for Xolair and 42.2% for placebo. ). Improvements in measures of airflow (FEV1) and asthma symptoms were also observed.
Indication 2 - for the treatment of chronic idiopathic urticaria in adults and children at least 12 years of age
approved March of 2014
Xolair 150 or 300 mg SC every 4 weeks. Dosing is not dependent on serum IgE level or body weight.
The FDA approval of Xolair for chronic idiopathic urticaria in patients 12 years and older who remained symptomatic despite taking H1-antihistamines was assessed using a scale known as the average (mean) weekly Itch Severity Score (ISS) at Week 12. The weekly ISS has potential scores ranging from 0 to 215. In ASTERIA I, Xolair 150 mg improved ISS from the starting measurement by 47 percent (-6.7) and Xolair 300 mg improved ISS from the starting measurement by 66 percent (-9.4) at Week 12, compared to a 25 percent (-3.6) score improvement for patients who received placebo. Also, a larger proportion of patients (36 percent) treated with Xolair 300 mg reported no itch and no hives at Week 12, compared to patients treated with Xolair 150 mg (15 percent), and patients in the placebo group (9 percent) . Similar results were observed for the ASTERIA II study.
Indication 3 - for the the treatment of nasal polyps in adult patients 18 years of age and older
approved December 2020
Xolair 75 to 600 mg SC every 2 or 4 weeks. Determine dose (mg) and dosing frequency by serum total IgE level (IU/mL)
The FDA approval of Xolair for nasal polyps was based on results from the Phase III POLYP 1 and POLYP 2 trials. Both trials showed that adult patients with nasal polyps who had an inadequate response to nasal corticosteroids and received Xolair had statistically significant greater improvement from baseline at Week 24 in Nasal Polyp Score (NPS) and weekly average Nasal Congestion Score (NCS) than patients who received placebo. In POLYP 1 and POLYP 2, the mean change from baseline at Week 24 for Xolair compared to placebo were: NPS, -1.1 vs 0.1 and -0.9 vs -0.3, respectively; NCS, -0.9 vs -0.4 and -0.7 vs -0.2, respectively.
Indication 4- for children and adults with one or more food allergies
approved February of 2024
Xolair 75 mg to 600 mg SC every 2 or 4 weeks. Determine dose (mg) and dosing frequency by serum total IgE level (IU/mL), measured before the start of treatment, and body weight (kg). See the dose determination chart on drug label.
The FDA approval is based on positive data from the Phase III OUtMATCH study, which evaluated Xolair in patients aged 1 to 55 years allergic to peanuts and at least two other food allergens, including milk, egg, wheat, cashew, hazelnut and walnut. Patients entered the OUtMATCH study unable to tolerate up to 100 mg of peanut protein (equivalent to about one third of a peanut), and up to 300 mg each of milk, egg and cashew protein. After 16 to 20 weeks of treatment with Xolair or placebo, each participant completed four food challenges, receiving gradually increasing amounts of foods they are allergic to (and a placebo ingredient), in order to assess their ability to consume a single dose of at least 600 mg of peanut protein (primary endpoint), and a single dose of at least 1,000 mg of milk, egg or cashew protein (secondary endpoints) without experiencing moderate to severe allergic symptoms.
Study results showed a statistically significant higher proportion of patients (68%) treated with Xolair for 16 to 20 weeks tolerated at least 600 mg of peanut protein without moderate to severe allergic symptoms, compared to 5% of those treated with placebo. This amount is equivalent to approximately two and a half peanuts or half a teaspoon of regular peanut butter.
In addition, a statistically significant higher proportion of patients treated with Xolair compared to placebo tolerated at least 1,000 mg of protein from milk (66% vs. 11%), egg (67% vs. 0%) or cashew (42% vs. 3%) without moderate to severe allergic symptoms. This amount is equivalent to approximately two tablespoons of 1% milk, one-quarter of an egg or three and a half cashews. While patients in the study tolerated these amounts of food, treatment with Xolair should be used with continued food allergen avoidance.