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For Patients and Caregivers

Allergic Asthma Trials—XOLAIR Efficacy & Safety Profile

XOLAIR has been shown to significantly reduce exacerbations in appropriate allergic asthma patients uncontrolled on inhaled corticosteroids (ICS).1

Multiple clinical studies were done to analyze the efficacy and safety of XOLAIR in 2 patient populations:

  1. Adolescent and adult patients aged ≥12 years. See data.
  2. Pediatric patients aged 6 to <12 years. See data.

See additional information for patient baseline characteristics. Please see full safety information. 

Adolescent & Adult Study Results (≥12 Years) Pediatric Study Results (6 to <12 Years) Patient Baseline Characteristics
Adolescent & Adult Study Results (≥12 Years)

XOLAIR Clinical Studies in Adolescent and Adult Patients Aged ≥12 Years

Results for Studies 1 and 2

Two Pivotal Studies in Moderate to Severe Asthma Confirmed XOLAIR Significantly Reduced Exacerbations

Graph showing clinical study results. Xolair displayed up to a 75% decrease in exacerbations vs control in moderate to severe asthma in the ICS-stable phase and up to a 50% decrease in exacerbations vs control in moderate to severe asthma in the ICS-reduction phase.

Study design for Studies 1 and 2: Identical 28-week, randomized, double-blind, placebo-controlled studies evaluating the number of exacerbations in a total of 1071 patients aged 12 to 76 years with moderate to severe persistent allergic asthma who were symptomatic despite ICS treatment.1,6,7

Patients received XOLAIR or placebo every 2 or 4 weeks for 16 weeks with an unchanged BDP dose unless an acute exacerbation necessitated an increase. Patients then entered a 12-week ICS-reduction phase during which ICS dose reduction was attempted in a stepwise manner.1,6

Primary endpoint: number of exacerbations.1,6

 

More XOLAIR Patients had Zero Exacerbations1*

Graph showing up to 87.6% of Xolair allergic asthma patients had zero exacerbations.

XOLAIR Reduced Exacerbations to Zero in the Majority of Allergic Asthma Patients Studied. What Could it do for Yours?

 

Significantly Fewer Patients Had ≥1 Exacerbation(s) With XOLAIR1§

Table showing clinical trial results of the percentage of Xolair allergic asthma patients with one
Table showing clinical trial results of the percentage of Xolair allergic asthma patients with one

Results from Study 3:

Study design for Study 3: A 32-week, randomized, double-blind, placebo-controlled study designed to evaluate ICS reduction in 341 patients aged 12 to 76 years with severe allergic asthma. Exacerbation reduction was also evaluated as a secondary endpoint; however, this study was not powered to show statistical differences in exacerbation reduction.1

  • Unlike in Studies 1 and 2, there was no restriction on screening FEV1, and LABAs were allowed1
  • Patients were receiving ≥1000 μg/d ICS (fluticasone), and a subset was also receiving OCS1  
    • No reductions in exacerbations were seen in patients who required oral steroids as maintenance therapy1

 

Exacerbation was defined as a worsening of asthma that required treatment with systemic corticosteroids or a doubling of the patient’s baseline ICS dose.

Patients were stratified by use of ICS only or ICS with concomitant OCS. Patients received XOLAIR for 16 weeks with an unchanged corticosteroid dose unless an acute exacerbation necessitated an increase. Patients then entered a 16-week ICS-reduction phase during which ICS dose reduction was attempted in a stepwise manner.1,5

Percentage of patients with ≥1 exacerbation in Study 31

In the ICS-stable phase:

  • 15.9% of patients taking XOLAIR + ICS (n=126) experienced ≥1 exacerbation vs 15% of those taking placebo + ICS (n=120)
    • Difference of 0.9 (95% CI: -97, 13.7)
  • 32% of patients taking XOLAIR + ICS + OCS (n=50) experienced ≥1 exacerbation vs 22.2% of those taking placebo + ICS + OCS (n=45)
    • Difference of 9.8 (95% CI: -10.5, 31.4)

In the ICS-reduction phase:

  • 22.2% of patients taking XOLAIR + ICS (n=126) experienced ≥1 exacerbation vs 26.7% of those taking placebo + ICS (n=120)
    • Difference of -4.4 (95% CI: -17.6, 7.4)
  • 42% of patients taking XOLAIR + ICS + OCS (n=50) experienced ≥1 exacerbation vs 42.2% of those taking placebo + ICS + OCS (n=45)
    • Difference of -0.2 (95% CI: -22.4, 20.1)
  • The number of exacerbations in the XOLAIR group was similar to that in the control group
  • The absence of an observed treatment effect may be related to differences in patient population compared with Studies 1 and 2, study sample size, or other factors
  • A reduction in exacerbations was not observed in XOLAIR-treated patients who had a FEV1 >80% predicted at the time of randomization or in patients who required OCS as maintenance therapy

CI=confidence interval; FEV1=forced expiratory volume in 1 second; LABA=long-acting beta2-agonist; OCS=oral corticosteroids.

Adverse Reactions from Placebo Controlled Trials

Adverse Reactions from Placebo Controlled Trials

Adverse Reactions ≥1% More Frequent in XOLAIR-Treated Adult or Adolescent Patients 12 years of Age and Older in Placebo-controlled Asthma Trials1

Table showing the adverse reactions of XOLAIR in allergic asthma

There were no differences in the incidence of adverse reactions based on age (among patients under 65), gender or race.

Post Hoc Analyses of Pooled Data from Studies 1 and 2:

Exacerbation Data Across Patient Groups

Limitations of these analyses of pooled data from Studies 1 and 2 include that they are post hoc (ie, not prespecified) and that the 95% confidence intervals were calculated within each investigated range of IgE levels, number of positive allergens, or eosinophil counts, which does not afford the ability to compare the subgroups to each other directly. These analyses do not allow the inference of any sort of trend with increasing IgE levels, number of positive allergens, or eosinophil counts, as no trend tests were performed.5,22

In allergic asthma patients aged ≥12 years:

Chart 1 is showing the XOLAIR data across total IgE levels. Chart 2 shows XOLAIR data across number of positive perennial allergens. Chart 3 shows XOLAIR data across eosinophil count.

Select baseline characteristics22

Chart showing select baseline characteristics of study participants

In these post hoc analyses, an asthma exacerbation was defined as the worsening of asthma requiring treatment with oral or intravenous corticosteroids for at least 3 days (adapted from 2009 American Thoracic Society/European Respiratory Society).24

BDP=beclomethasone dipropionate; SD=standard deviation; SE=standard error.

Pediatric Study Results (6 to <12 Years)

Clinical Studies in Pediatric Patients Aged 6 to <12 Years

XOLAIR is the First Biologic Proven to Reduce Exacerbations in Pediatric Patients with Allergic Asthma1,25

Xolair reduced asthma exacerbations in patients aged 6 to less than 12 years.

Study design: A 52-week, multicenter, randomized, double-blind, placebo-controlled study of 628 patients aged 6 to <12 years with moderate to severe allergic asthma evaluated XOLAIR as add-on therapy to ICS with or without additional controller medications. Patients received XOLAIR or placebo every 2 or 4 weeks for 24 weeks during the fixed-steroid treatment phase. Steroid doses remained constant from baseline unless an acute exacerbation necessitated an increase. Patients then entered a 28-week period during which steroid adjustment was allowed.1,25,26

Throughout the study, both groups were allowed to use additional controller medications, including inhaled and nebulized beta2-agonists and LTRA.25

Primary measure: rate of asthma exacerbations during the 24-week period.1

Exacerbation was defined as a worsening of asthma symptoms requiring doubling of baseline ICS dose for at least 3 days and/or treatment with rescue systemic corticosteroids for at least 3 days.1

XOLAIR Has an Established Safety Profile in Over 900 Pediatric Patients Aged 6 to <12 Years With Allergic Asthma in Clinical Studies1

Most Common Adverse Reactions in Pediatric Patients
Safety data described reflect XOLAIR exposure for 926 patients aged 6 to <12 years, including 583 patients exposed for 6 months and 292 exposed for 1 year or more, in either placebo-controlled or other controlled studies.1
Patient Baseline Characteristics

Select Baseline Characteristics in Allergic Asthma Patients Aged ≥12

Broad Range of Patients Included1,5-7

Chart showing the select baseline characteristics in allergic asthma patients age 12 to 76 who participated in Xolair clinical studies.

Clinical Studies in Pediatric Patients Aged 6 to <12 Years

A Broad Range of Patients Was Included1,5,25

Xolair clinical trials and the select baseline characteristics in allergic asthma patients ages 6 to less than 12 years.

Add-on anti-IgE (omalizumab) treatment for patients aged ≥6 with moderate to severe allergic asthma that is uncontrolled on step 4-5 treatment.27,28

—Global Initiative for Asthma (GINA), 2021 Guideline Update

IMPORTANT SAFETY INFORMATION

INDICATIONS
XOLAIR® (omalizumab) is indicated for:

  • Adults and pediatric patients 6 years of age and older 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.

    Limitations of Use: XOLAIR is not indicated for the relief of acute bronchospasm, status asthmaticus, or for treatment of other allergic conditions.

  • Add-on maintenance treatment of nasal polyps in adult patients 18 years of age and older with inadequate response to nasal corticosteroids.

  • Chronic spontaneous urticaria (CSU) in adults and adolescents 12 years of age and older who remain symptomatic despite H1 antihistamine treatment.

    Limitations of Use: XOLAIR is not indicated for treatment of other forms of urticaria.

WARNING: Anaphylaxis

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 as early as after the first dose of XOLAIR, but also has occurred beyond 1 year after beginning regularly administered treatment. Because of the risk of anaphylaxis, initiate XOLAIR therapy in a healthcare setting and closely observe patients for an appropriate period of time after XOLAIR administration. Health care providers administering XOLAIR should be prepared to manage anaphylaxis which can be life-threatening. Inform patients of the signs and symptoms of anaphylaxis and instruct them to 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.

CONTRAINDICATIONS

XOLAIR is contraindicated in patients with a severe hypersensitivity reaction to XOLAIR or to any ingredient of XOLAIR.

WARNINGS AND PRECAUTIONS

Anaphylaxis
Anaphylaxis has been reported to occur after administration of XOLAIR in premarketing clinical trials and in postmarketing spontaneous reports. In premarketing clinical trials in patients with asthma, anaphylaxis was reported in 3 of 3507 (0.1%) patients. Anaphylaxis occurred with the first dose of XOLAIR in two patients and with the fourth dose in one patient. The time to onset of anaphylaxis was 90 minutes after administration in two patients and 2 hours after administration in one patient.

A case-control study showed that, among XOLAIR users, patients with a history of anaphylaxis to foods, medications, or other causes were at increased risk of anaphylaxis associated with XOLAIR, compared to those with no prior history of anaphylaxis.

In postmarketing spontaneous reports, the frequency of anaphylaxis attributed to XOLAIR use was estimated to be at least 0.2% of patients based on an estimated exposure of about 57,300 patients from June 2003 through December 2006. Approximately 60% to 70% of anaphylaxis cases have been reported to occur within the first three doses of XOLAIR, with additional cases occurring sporadically beyond the third dose.

Initiate XOLAIR only in a healthcare setting equipped to manage anaphylaxis which can be life-threatening. Observe patients closely for an appropriate period of time after administration of XOLAIR, taking into account the time to onset of anaphylaxis seen in premarketing clinical trials and postmarketing spontaneous reports. Inform patients of the signs and symptoms of anaphylaxis, and instruct them to seek immediate medical care should signs or symptoms occur.

Once XOLAIR therapy has been established, administration of XOLAIR Prefilled Syringe outside of a healthcare setting by a patient or a caregiver may be appropriate for selected patients. Patient selection, determined by the healthcare provider in consultation with the patient, should take into account the pattern of anaphylaxis events seen in premarketing clinical trials and postmarketing spontaneous reports, as well as individual patient risk factors (e.g. prior history of anaphylaxis), ability to recognize signs and symptoms of anaphylaxis, and ability to perform subcutaneous injections with XOLAIR Prefilled Syringe with proper technique according to the prescribed dosing regimen and Instructions for Use.

Discontinue XOLAIR in patients who experience a severe hypersensitivity reaction.

Malignancy
Malignant neoplasms were observed in 20 of 4127 (0.5%) XOLAIR-treated patients compared with 5 of 2236 (0.2%) control patients in clinical studies of adults and adolescents (≥12 years of age) with asthma and other allergic disorders. The observed malignancies in XOLAIR-treated patients were a variety of types, with breast, non-melanoma skin, prostate, melanoma, and parotid occurring more than once, and five other types occurring once each. The majority of patients were observed for less than 1 year. The impact of longer exposure to XOLAIR or use in patients at higher risk for malignancy (e.g., elderly, current smokers) is not known.

A subsequent 5-year observational study of 5007 XOLAIR-treated and 2829 non-XOLAIR-treated adolescent and adult patients with moderate to severe persistent asthma and a positive skin test reaction or in vitro reactivity to a perennial aeroallergen found that the incidence rates of primary malignancies (per 1000 patient years) were similar in both groups (12.3 vs 13.0, respectively). Study limitations which include the observational study design, the bias introduced by allowing enrollment of patients previously exposed to XOLAIR (88%), enrollment of patients (56%) while a history of cancer or a premalignant condition were study exclusion criteria, and the high study discontinuation rate (44%) preclude definitively ruling out a malignancy risk with XOLAIR.

Acute Asthma Symptoms and Deteriorating Disease
XOLAIR has not been shown to alleviate asthma exacerbations acutely. Do not use XOLAIR to treat acute bronchospasm or status asthmaticus. Patients should seek medical advice if their asthma remains uncontrolled or worsens after initiation of treatment with XOLAIR.

Corticosteroid Reduction
Do not discontinue systemic or inhaled corticosteroids abruptly upon initiation of XOLAIR therapy for asthma or nasal polyps. Decrease corticosteroids gradually under the direct supervision of a physician. In CSU patients, the use of XOLAIR in combination with corticosteroids has not been evaluated.

Eosinophilic Conditions
In rare cases, patients with asthma on therapy with XOLAIR may present with serious systemic eosinophilia, sometimes presenting with clinical features of vasculitis consistent with Churg-Strauss syndrome. These events usually, but not always, have been associated with the reduction of oral corticosteroid therapy. Physicians should be alert to eosinophilia, vasculitic rash, worsening pulmonary symptoms, cardiac complications, and/or neuropathy presenting in their patients. A causal association between XOLAIR and these underlying conditions has not been established.

Fever, Arthralgia, and Rash
In post-approval use, some patients have experienced a constellation of signs and symptoms, including arthritis/arthralgia, rash, fever, and lymphadenopathy with an onset 1 to 5 days after the first or subsequent injections of XOLAIR. These signs and symptoms have recurred after additional doses in some patients. Physicians should stop XOLAIR if a patient develops this constellation of signs and symptoms.

Parasitic (Helminth) Infection
Monitor patients at high risk of geohelminth infection while on XOLAIR therapy. Insufficient data are available to determine the length of monitoring required for geohelminth infections after stopping XOLAIR treatment.

Laboratory Tests
Due to formation of XOLAIR:IgE complexes, serum total IgE levels increase following administration of XOLAIR and may remain elevated for up to 1 year following discontinuation of XOLAIR. Do not use serum total IgE levels obtained less than 1 year following discontinuation to reassess the dosing regimen for asthma or nasal polyps patients, because these levels may not reflect steady state free IgE levels.

ADVERSE REACTIONS

Asthma
In patients ≥12 years of age, the most common adverse reactions (≥1% more frequent in XOLAIR-treated patients) were: arthralgia (8%), pain (general) (7%), leg pain (4%), fatigue (3%), dizziness (3%), fracture (2%), arm pain (2%), pruritus (2%), dermatitis (2%), and earache (2%). In pediatric patients 6 to <12 years of age, the most commonly observed adverse reactions (≥3% more frequent in XOLAIR-treated pediatric patients) were: nasopharyngitis, headache, pyrexia, upper abdominal pain, pharyngitis streptococcal, otitis media, viral gastroenteritis, arthropod bite, and epistaxis.

Nasal Polyps
The most common adverse reactions (≥3% incidence in XOLAIR-treated patients and more frequent than placebo) included: headache (8.1%), injection site reaction (5.2%), arthralgia (3.0%), upper abdominal pain (3.0%), and dizziness (3.0%).

Chronic Spontaneous Urticaria
The most common adverse reactions (≥2% XOLAIR-treated patients and more frequent than in placebo) for XOLAIR 150 mg and 300 mg, respectively, included: headache (12%, 6%), nasopharyngitis (9%, 7%), arthralgia (3%, 3%), viral upper respiratory infection (2%, 1%), nausea (1%, 3%), sinusitis (1%, 5%), upper respiratory tract infection (1%, 3%), and cough (1%, 2%).

Injection Site Reactions

Asthma
In adults and adolescents with asthma, injection site reactions of any severity occurred at a rate of 45% in XOLAIR-treated patients compared with 43% in placebo-treated patients. Severe injection site reactions occurred more frequently in XOLAIR‑treated patients compared with patients in the placebo group (12% vs 9%, respectively). The types of injection site reactions in asthma studies included: bruising, redness, warmth, burning, stinging, itching, hive formation, pain, indurations, mass, and inflammation.

Nasal Polyps
Injection site reactions occurred at a rate of 5.2% in XOLAIR-treated patients compared with 1.5% in placebo-treated patients. Injection site reactions were mild to moderate severity and none resulted in study discontinuation.

Chronic Spontaneous Urticaria
Injection site reactions of any severity occurred in more XOLAIR-treated patients (11 patients [2.7%] at 300 mg, 1 patient [0.6%] at 150 mg) compared with 2 placebo-treated patients (0.8%). The types of injection site reactions included: swelling, erythema, pain, bruising, itching, bleeding, and urticaria. None of the events resulted in study discontinuation or treatment interruption.

Cardiovascular and Cerebrovascular Events from Clinical Studies in Patients with Asthma
A 5-year observational study was conducted in 5007 XOLAIR-treated and 2829 non-XOLAIR-treated patients ≥12 years of age with moderate to severe persistent asthma and a positive skin test reaction to a perennial aeroallergen to evaluate the long term safety of XOLAIR, including the risk of malignancy. Similar percentages of patients in both cohorts were current (5%) or former smokers (29%). Patients had a mean age of 45 years and were followed for a mean of 3.7 years. More XOLAIR-treated patients were diagnosed with severe asthma (50%) compared to the non-XOLAIR-treated patients (23%). A higher incidence rate (per 1000 patient-years) of overall cardiovascular and cerebrovascular serious adverse events (SAEs) was observed in XOLAIR-treated patients (13.4) compared to non-XOLAIR-treated patients (8.1). Increases in rates were observed for transient ischemic attack (0.7 vs 0.1), myocardial infarction (2.1 vs 0.8), pulmonary hypertension (0.5 vs 0), pulmonary embolism/venous thrombosis (3.2 vs 1.5), and unstable angina (2.2 vs 1.4), while the rates observed for ischemic stroke and cardiovascular death were similar among both study cohorts. The results suggest a potential increased risk of serious cardiovascular and cerebrovascular events in patients treated with XOLAIR, however the observational study design, the inclusion of patients previously exposed to XOLAIR (88% for a mean of 8 months), baseline imbalances in cardiovascular risk factors between the treatment groups, an inability to adjust for unmeasured risk factors, and the high study discontinuation rate (44%) limit the ability to quantify the magnitude of the risk.

Pregnancy
Data with XOLAIR use in pregnant women are insufficient to inform on drug associated risk.

You may report side effects to the FDA at (800) FDA-1088 or www.fda.gov/medwatch. You may also report side effects to Genentech at (888) 835-2555 or Novartis Pharmaceuticals Corporation at (888) 669-6682.

Please see full Prescribing Information, including Boxed WARNING and Medication Guide, for additional Important Safety Information.

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