Subject: Xolair (Omalizumab)for Allergic Asthma Original Effective Date: 10/26/2011 Policy Number: MCP-001 Revision Date(s):10/26/2011; 12/29/2015; 7/18/2016 Review Date(s): 10/26/2011; 12/29/2015; 7/18/2016, 9/19/2017, 7/10/2018 DISCLAIMER This Molina Clinical Policy (MCP) is intended to facilitate the Utilization Management process. It expresses Molina's determination as to whether certain services or supplies are medically necessary, experimental, investigational, or cosmetic for purposes of determining appropriateness of payment. The conclusion that a particular service or supply is medically necessary does not constitute a representation or warranty that this service or supply is covered (i.e., will be paid for by Molina) for a particular member. The member's benefit plan determines coverage. Each benefit plan defines which services are covered, which are excluded, and which are subject to dollar caps or other limits. Members and their providers will need to consult the member's benefit plan to determine if there are any exclusion(s) or other benefit limitations applicable to this service or supply. If there is a discrepancy between this policy and a member's plan of benefits, the benefits plan will govern. In addition, coverage may be mandated by applicable legal requirements of a State, the Federal government or CMS for Medicare and Medicaid members. CMS's Coverage Database can be found on the CMS website. The coverage directive(s) and criteria from an existing National Coverage Determination (NCD) or Local Coverage Determination (LCD) will supersede the contents of this MCP document and provide the directive for all Medicare members. SUMMARY This policy addresses the coverage of Xolair (Omalizumab) for the treatment of moderate to severe persistent asthma in adults and adolescents 6 years and older when appropriate criteria are met. The intent of the Xolair (omalizumab) drug policy is to ensure appropriate selection of patients for therapy based on product labeling, clinical guidelines, and clinical studies. *REFER TO MCP-178 for Xolair (Omalizumab) for Chronic Idiopathic Urticaria ∑ Asthma is one of the most common long-term diseases in children 1 , affecting about 6.3 million people younger than 18 in the U.S or one in 12 children in the U.S. g The American Academy of Pediatrics estimates that between 70 and 80 percent of school-aged children with asthma also have allergies, which are among the most common triggers for asthma. H ∑ Omalizumab is a monoclonal antibody that reduces the levels of circulating IgE and inhibits binding of IgE to mast cells, to prevent the activation of the allergic cascade and decrease inflammation. Omalizumab is an adjunct therapy option for select patients with allergic asthma. It is indicated for patients who have severe allergic asthma with elevated IgE levels and have not achieved asthma control with other drug therapies. B ∑ Achieving and maintaining asthma control is the goal of treatment. Controller medications suppress the inflammatory causes of asthma to provide clinical control over the long term, whereas reliever medications relieve bronchoconstriction quickly (2010 Global Strategy for Asthma Treatment and Prevention B ) ∑ There are no available data demonstrating that omalizumab is superior to preferred options recommended in treatment guidelines for moderate-to-severe persistent asthma. 3 Page 1 of 20
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Subject: Xolair (Omalizumab)for Allergic Asthma …...• July 2016: FDA Approves Xolair (omalizumab) for allergic asthma in children placing Xolair as the only biologic for children
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Subject: Xolair (Omalizumab)for Allergic Asthma Original Effective Date: 10/26/2011
¶ Airflow limitation: Forced expiratory volume in one second (FEV1) or peak expiratory flow (PEF) less than
80% of predicted level (after bronchodilator withhold*)
*Spirometry performed prior to the administration of bronchodilators (pre- and post-bronchodilator
administration)--bronchodilators have been withheld for a period of time.
‹ Based on the National Asthma Education and Prevention Program (NAEPP), moderate persistent
asthma is classified as daily daytime symptoms, night time awakenings of greater than once per week
but not nightly, daily use of short-acting beta2-agonist for symptom control, some limitation of normal
activity, FEV1 >60% but <80% of predicted value and FEV1/FVC reduced up to 5%. Severe
persistent asthma is classified as symptoms throughout the day, nighttime awakenings often 7 times
per week, use of short-acting beta2-agonist for symptom control, extreme limitation of daily activity,
FEV1 <60% of predicted, and FEV1/FVC reduced >5%. (NAEPP Expert Panel Report 3: Guidelines
for the Diagnosis and Management of Asthma, 2007)
‹ Patients in the clinical trials most often were required to have an FEV1 between 40% and 80% of
predicted. No patients were enrolled with an FEV1 greater than 80% of predicted.
‹ Data from omalizumab clinical trials did not support its efficacy in patients who had a baseline FEV1
greater than 80%, or who required oral steroids as maintenance therapy. In all three of the trials, a
reduction of asthma exacerbations was not observed in the Xolair-treated patients who had FEV1 >
80% at the time of randomization. Reductions in exacerbations were not seen in patients who
required oral steroids as maintenance therapy.
Note:�Moderate persistent asthma: FEV1 or PEF 60%-80% of predicted�Severe persistent asthma: FEV1 or PEF ≤ 60% predicted�
3.� Age/Gender/Other restrictions [ALL]
¶ 6 years of age or older ‹ Safety and efficacy in pediatric patients with asthma below 6 years of age have not been established.a
¶ Members age 6 to <12 years: [BOTH]
û Body weight between 20 kg (44 lbs) and 150 kg (330 lbs)
û Pre-treatment serum total IgE levels of 30 to 1300 IU/mL. Documentation (lab results) required. NOTE: Limited clinical information is available regarding Xolair use for pediatric patients between the
ages of 6- 12 years old with IgE levels of > 1300 IU/mL.
¶ Members age ≥12 years : [BOTH]
û Body weight between 30 kg (66 lbs) and 150 kg (330 lbs)
û Pre-treatment serum total IgE levels of 30 to 700 IU/mL. Documentation (lab results) required.
NOTE: Limited clinical information is available regarding Xolair use for patients over the age of 12 with
IgE levels >700 IU/mL.
¶ Member is a non-smoker OR smoking cessation has been at least 6 months
‹ Patients currently smoking were excluded in pivotal trials, thus the safety and efficacy of the drug for
a person who smokes is not known. a
¶ Underlying conditions or triggers for asthma or pulmonary disease are being maximally managed
Page 4 of 20
4.� Step/Conservative Therapy/Other condition Requirements [ALL] NHLBI recommended first-line STEP5 asthma therapies for persistent asthma including use of as-needed short-acting beta-
agonists (SABAs), high-dose inhaled corticosteroids (ICS), and inhaled long-acting beta-agonists (LABAs), along with strict
allergen (environmental) control. Oral corticosteroids are recommended for exacerbations, as well as STEP 6 therapy.F
¶ Omalizumab not being prescribed as monotherapy for asthma (will be used in combination with other
medications for long-term control of asthma)
¶ Asthma symptoms have not been adequately controlled by inhaled corticosteroids after at least 3 months (90
days) of therapy. Inadequate control on inhaled corticosteroids as documented by ONE (1) or more of the
following: [ONE]
û Requirement for systemic (oral, parenteral) corticosteroids to control exacerbations of asthma
û Frequent severe exacerbations that often require emergency room visits, unscheduled office visits
and/or hospitalizations
û Excessive use of rescue medications and/or oral steroids OR increasing need for short-acting inhaled
beta2 agonists for symptoms (not including preventive use for exercise-induced asthma)
û Limitations or impairment in activities of daily living, such as work, school, exercise and/or sleep
û Nocturnal symptoms/awakening
û Lung function (PEF or FEV1) < 80% predicted or personal best (without administration of
bronchodilator or after bronchodilator withhold)
¶ Member's symptoms are inadequately controlled [as documented in above criterion] after a compliant
regimen of at least 3 months of the following COMBINATION THERAPY: [A OR B]
Xolair (Omalizumab) may be authorized for continuation of therapy if meet ALL of the following criteria are met: [ALL]
1.� Initial Coverage Criteria
ß Member currently meets ALL initial coverage criteria
ß Consultation notes must be submitted for initial request and for continuation of treatment requests at least
ONCE annually. The prescribing physician should periodically reassess the need for continuation of therapy
based on the member’s disease severity and level of asthma control. Continuation of therapy requires
submission of relevant medical records or chart notes documenting continued efficacy of Xolair.
2. Compliance
ß Adherence to therapy at least 85% of the time as verified by Prescriber and member’s medication fill history
(review Rx history for compliance), including:
û Adherent to the prescribed medication regimen
û Tolerance to therapy
û No severe adverse reactions or drug toxicity
NOTE: Therapy may be discontinued due to poor adherence upon recommendation of the Molina Medical
Director when adherence < 85% has been demonstrated in at least two months during the course of therapy
NOTE: History of non-compliance or non-adherence as verified by member’s medication fill history or
prescription drug profile may result in continuation of therapy request not being authorized. [MOLINA
MEDICAL/PHARMACY REVIEWER TO VERIFY
‹ Optimal clinical response to omalizumab requires strict compliance with dosing, as there is a 6 to 12
week lag before beneficial effects are apparent. (Effects are not immediate and explain the various phases
that are included in study protocols.)
3.� Labs/Reports/Documentation required [ALL]
Documentation of significant reduction in corticosteroid dosage or asthma exacerbations as demonstrated by:
¶ Maintenance therapy with an oral/inhaled corticosteroid (prior to initiation of Xolair) has resulted in the
reduction of oral/inhaled corticosteroid dose
‹ In the pivotal trial, Xolair-treated patients had a statistically significant reduction in the rate of
exacerbations (exacerbation was defined as worsening of asthma that required treatment with
systemic corticosteroids or a doubling of the baseline ICS dose), but other efficacy variables such as
nocturnal symptom scores, beta-agonist use, and measures of airflow (FEV1) were not significantly
different in Xolair-treated patients compared to placebo.
¶ Xolair (omalizumab) has resulted in clinical improvement as documented by ONE (1) or more of the
following from pre-Xolair baseline. Documentation required: [ONE]
û Improvement in lung function (increase in percent predicted FEV1 or PEF) from pre-treatment
baseline
û Decreased utilization of rescue medications
û Decreased frequency of exacerbations (defined as worsening of asthma that requires increase in
inhaled corticosteroid dose or treatment with systemic corticosteroids)
û Decreased frequency of unscheduled clinic, urgent care or emergency department visits
Page 7 of 20
û Reduction in reported symptoms: chest tightness, coughing, shortness of breath, nocturnal wakening
wheezing, sustained improvement in ACT scores
û Reduction use of ICS, leukotriene or beta agonist therapy
û Reduction in reported symptoms (decrease in asthma symptom score), as evidenced by decreases in
frequency or magnitude of one or more of the following symptoms:
o Asthma attacks
o Chest tightness or heaviness
o Coughing or clearing throat
o Difficulty taking deep breath or difficulty breathing out
o Shortness of breath
o Sleep disturbance, night wakening, or symptoms upon awakening
o Tiredness
o Wheezing/heavy breathing
NOTE: In Xolair clinical trials, subjects had a reduced number of asthma exacerbations, reduced duration of
asthma exacerbations, reduced corticosteroids usage, reduced number of rescue medications, improvements in
pulmonary function tests, reduced number of hospitalizations/emergency room visits.
4.� Discontinuation of Treatment [ANY]
Discontinue treatment if ANY of the following conditions applies: [ANY]
ß Intolerable adverse effects or absence of unacceptable toxicity from the drug
‹ Examples of unacceptable toxicity include the following: symptoms of anaphylaxis (bronchospasm,
hypotension, syncope, urticara, and/or angioedema); malignancy; symptoms similar to serum
sickness (fever, arthralgia, and rash); eosinophilic conditions, including vasculitic rash, worsening
pulmonary symptoms, cardiac complications, and/or neuropathy, especially upon reduction of oral
corticosteroids
ß Persistent and uncorrectable problems with adherence to treatment
ß Poor response to treatment as evidenced by physical findings and/or clinical symptoms
ß Contraindications/Exclusions to therapy
û Non-FDA approved indications
û Severe hypersensitivity reaction to omalizumab or any component of the formulation
Exclusions [ANY]
û Treatment to relieve acute bronchospasm or status asthmaticusa
‹ Not indicated for acute bronchospasm or status asthmaticus.a Omalizumab has not been
shown to alleviate acute asthma exacerbations and should not be used for the treatment of
acute bronchospasm or status asthmaticus.
Page 8 of 20
ADMINISTRATION, QUANTITY LIMITATIONS, AND AUTHORIZATION PERIOD
1.� Recommended Dosage [ALL]
¶ Dose requested is consistent with corresponding weight and IgE level per manufacturer’s dosing chart
¶ For subcutaneous (SC) administration only. Divide doses of more than 150 mg among more than one
injection site to limit injections to not more than 150 mg per site.
¶ Asthma: 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). Omalizumab dosage
and dosing frequency are determined based on total serum IgE concentrations and body weight measured
before the start of treatment. Dosage should be adjusted accordingly if the patient's body weight change
substantially since apparent clearance of the drug is proportional to body weight.
¶ Adults and Adolescents (12 Years of Age and Older): Table 1 and Table 2 (per FDA-approved labeling)
¶ Pediatric patients 6 to <12 years of age: Table 3 (per FDA-approved labeling)
Table 1. ADMINISTRATION EVERY 4 WEEKS
Every 4 Weeks for Adults and Adolescents (12 Years of Age and Older) with Asthma
Pre-treatment
Serum IgE
(IU/mL)
Body Weight (kg)
30-60 >60-70 >70-90 >90-150
> 30-100 150 150 150 300
>100-200 300 300 300
>200-300 300
>300-400 See Table 2
>400-500 Below
>500-600
Table 2. ADMINISTRATION EVERY 2 WEEKS
Every 2 Weeks for Adults and Adolescents (12 Years of Age and Older) with Asthma
Pre-treatment
Serum IgE
(IU/mL)
Body Weight (kg)
30-60 >60-70 >70-90 >90-150
> 30-100 See Table 1
>100-200 Above 225
>200-300 225 225 300
>300-400 225 225 300
>400-500 300 300 375
>500-600 300 375
>600-700 375 Do Not Dose
Efficacy and dosing of omalizumab in asthma patients whose weight is outside the range provided in the
standard dosing table for omalizumab has not been established (weight-IgE level combinations yielding doses
greater than 750 mg every 4 weeks were excluded from clinical trials).
Page 9 of 20
Table 3. Pediatric Patients with Asthma Who Begin Xolair Between the Ages of 6 to < 12 years old�Omalizumab Doses (mg) Administered by Subcutaneous Injection Every 2 or 4 Weeks*�
û The number of vials authorized will be determined based on the indication and dosing table provided
in the manufacturer product labeling. For asthma, patient-specific doses are determined based on pre-
treatment serum IgE levels, body weight in kg, and dosing frequency (every 2 weeks or every 4
weeks) [for chronic idiopathic urticaria, the quantity limit is 300mg every 4 weeks]
û Maximum of 6 vials per 30 days or maximum of 375mg every 2 weeks for up to 6 months
¶ Dispensing limit: Only a 1-month supply may be dispensed at a timea-e
¶ Duration of initial authorization: 6 months
¶ Continuation of treatment: Re-authorization for continuation of treatment is required every 6 months to
determine continued need based on documented positive clinical response. Subsequent renewals will be
authorized upon verification of marked clinical improvement demonstrated by a reduction in asthma related
exacerbations
¶ Duration of continuation of treatment: May be authorized up to 6 months at a time ‹ The optimal duration of therapy in patients who experience clinical benefit has not been determined. Patients
who respond are generally continued on the drug long-term. Long-term dosing should be adjusted for changes
in body weight. There are no data exploring whether patients may require more or less omalizumab to control
symptoms over time. Reductions in the omalizumab dose below the recommended formula (0.016 mg/kg per
international units/mL of IgE per month) are likely to result in a loss of efficacy.7
Page 10 of 20
3.� Route of Administration [ALL]
¶ Xolair (Omalizumab) is considered a provider-administered medication and requires supervision of therapy
by a physician specializing in Allergy or Pulmonary Medicine. Omalizumab is not considered a self-injectable
medication for safety reasons. Medical observation for hypersensitivity reactions is necessary following
omalizumab administration.
‹ Administer only in a healthcare setting prepared to manage anaphylaxis that can be life-threatening
and observe patients for an appropriate period of time after administration.a-dAnaphylaxis, presenting
as bronchospasm, hypotension, syncope, urticaria, and/or angioedema of the throat or tongue, has
been reported to occur after administration of Xolair.
¶ Molina Healthcare supports administering injectable medications in various settings, provided that those
services are furnished in the most appropriate and cost-effective setting that are supportive of the member’s
medical condition and unique needs. The decision on the most appropriate setting for administration is based
on the member’s current medical condition and any required monitoring or additional services that may
coincide with the delivery of the specific medication.
Page 11 of 20
COVERAGE EXCLUSIONS
This policy only addresses the indication of Xolair (Omalizumab) for the treatment of moderate to severe persistent
asthma when appropriate criteria are met.
All other uses of Xolair (Omalizumab) that are not an FDA-approved indication or not included in the ‘Coverage Criteria’
section of this policy are considered experimental/investigational or not a covered benefit of this policy. This subject to
change based on research and medical literature, or at the discretion of Molina Healthcare.
¶ Acute Bronchospasm or Status Asthmaticus
The US Food and Drug Administration (FDA) has required the manufacturer of omalizumab to state in its
labeling that Xolair cannot be used to treat acute bronchospasm or status asthmaticus.a-d
¶ Baseline IgE serum levels above 700 IU/mL
‹ Data for use in patients with baseline IgE serum levels up to 1500 IU/mL are available (considered off-
label in the US). Omalizumab (Xolair) is only indicated in patients with elevated IgE levels and is dosed
according to IgE levels between 30 to 700 IU/ml. There is no established dose or benefit for IgE levels
outside of this range.
‹ Efficacy and dosing of omalizumab in asthma patients with IgE levels less than 30 or greater than 700
have not been established.a-d
‹ The majority of data on the use of omalizumab (Xolair) in patients with baseline IgE <30 or >700 IU/ml
are limited to case reports with inconsistent results of effectiveness.
‹ Monitoring IgE levels after administration of omalizumab are problematic, as IgE levels post-
administration measure both bound and unbound (free) IgE.
¶ Smokers
There is limited information on the efficacy and safety of omalizumab in patients who smoke. The decision to use
omalizumab in patients who have had unsuccessful attempts at smoking cessation should be made on a case-by-
case basis.
¶ Off-label Indications
Per DrugPointsc (DrugPoints, 2014), the ratings for all non-FDA labeled (off-label) indications for the use of
omalizumab are unchanged as follows:
• Allergic rhinitis, Prophylaxis- Recommendation for Adult & Pediatric Class llb, Strength of Evidence
Category B;
• Allergy to peanuts- Recommendation for Adult Class llb, Strength of Evidence Category B;
• Latex allergy- Recommendation for Adult Class llb, Strength of Evidence Category B;
• Subcutaneous immunotherapy, Adjunct- Recommendation for Adult & Pediatric Class IIb, Strength of
Evidence Category B
Page 12 of 20
SUMMARY
Asthma is a chronic inflammatory disorder of the airways in which many cells and cellular elements (multiple cytokines
and mediators, as well as potentially IgE-mediated events involving mast cells and basophils) play a role (in particular,
mast cells, eosinophils, T lymphocytes, macrophages, neutrophils and epithelial cells). Asthma is a chronic inflammatory
disorder of the airways in which many cells and cellular elements play a role: in particular, mast cells, eosinophils,
neutrophils (especially in sudden onset, fatal exacerbations, occupational asthma, and patients who smoke), T
lymphocytes, macrophages, and epithelial cells. In susceptible individuals, this inflammation causes recurrent episodes of
coughing (particularly at night or early in the morning), wheezing, breathlessness, and chest tightness. These episodes are
usually associated with widespread but variable airflow obstruction that is often reversible either spontaneously or with
treatment (NAEPP, 2007).
Drugs for asthma may be categorized as relievers (e.g., bronchodilators taken as needed for acute symptoms) or
controllers (principally inhaled corticosteroids or other anti-inflammatory agents taken regularly to achieve long-term
control of asthma).A,C
Omalizumab is a recombinant DNA-derived humanized IgG1к monoclonal antibody that selectively binds to human
immunoglobulin E (IgE). IgE is the antibody responsible for activation of allergic reactions and is important to the
pathogenesis of allergic diseases and the development and persistence of inflammation. Omalizumab is administered by
subcutaneous injection.
Omalizumab is indicated for the management of moderate to severe persistent asthma in patients who have a positive skin
test or in vitro reactivity to a perennial aeroallergen and whose symptoms are inadequately controlled with inhaled
corticosteroids.a, C However, some experts recommend use of omalizumab mainly for management of patients with severe
allergic asthma.C,A Safety and efficacy of omalizumab in the management of other allergic conditions have not been
established.a
Mechanism of Action
Asthma: Omalizumab is an IgG monoclonal antibody (recombinant DNA derived) that inhibits IgE binding to the high-
affinity IgE receptor on mast cells and basophils. By decreasing bound IgE, the activation and release of mediators in the
allergic response (early and late phase) is limited. Serum free IgE levels and the number of high-affinity IgE receptors are
decreased. Long-term treatment in patients with allergic asthma showed a decrease in asthma exacerbations and
corticosteroid usage.a-d
Chronic idiopathic urticaria: Omalizumab binds to IgE and lowers free IgE levels. Subsequently, IgE receptors (FceRI)
on cells down-regulate. The mechanism by which these effects of omalizumab result in an improvement of chronic
idiopathic urticaria symptoms is unknown.a-d
Safety and efficacy in other allergic conditions have not been established. Doses and dosing frequency are determined by
serum total IgE level (which is measured before the start of therapy) and the patient’s body weight. The drug is given
subcutaneously (SC).
GUIDELINES
∑ 2014 International European Respiratory Society/American Thoracic Society guidelines recommend a therapeutic
trial of omalizumab in adults and children with severe allergic asthma for improvement in asthma control and quality
of life and reduction in exacerbations and unscheduled health care utilization.D
∑ Current guidelines universally support omalizumab as an adjunctive treatment option in patients 12 years of age and
older who have severe persistent allergic (IgE-mediated) asthma that is inadequately controlled with the combination
of inhaled high-dose corticosteroids (ICS) and long-acting beta-agonists (LABAs).B Omalizumab has demonstrated
efficacy in pediatric patients 6 to 12 years of age with moderate-to-persistent allergic asthma and in patients requiring
medium-to-high ICS dosages; however, limited information on safety in children has resulted in its approval only for
Page 13 of 20
patients 12 years and older.B,a Omalizumab is associated with anaphylactic reactions, which are described in a black
box warning, as well as malignancies, joint pain, rash, fever, lymphadenopathy, injection-site pain, and bruising.a
Also, in a small number of patients in whom the anti-IgE therapy has facilitated steroid withdrawal, unmasking of
Churg-Strauss syndrome has been observed.B Omalizumab is not approved for use in patients younger than 12 years.
It is not available generically.a
∑ National Institute for Health and Clinical Excellence (NICE)
‹ NICE guidelines support the use of leukotriene receptor antagonists (LTRAs), theophylline, and oral
corticosteroids as adjunctive therapy in combination with ICS and LABA prior to initiating therapy with
omalizumab.E
‹ NICE guidelines (2010) recommended the use of omalizumab as add-on therapy to optimized standard
therapy only in patients 12 years of age and older with severe persistent (IgE mediated) asthma who have
been identified as having severe unstable disease. Optimized standard therapy is defined as a full trial of, and
documented compliance with, inhaled high dose corticosteroids and long acting beta2 agonists in addition to
leukotriene receptor antagonists, theophyllines, oral corticosteroids and beta-2 agonist tablets and smoking
cessation where clinically appropriate. Furthermore, in the clinical studies submitted to the FDA for approval
of omalizumab (Xolair), patients currently smoking were excluded.G
PIVOTAL TRIALS
The current indication for omalizumab is based principally on data from 3 multicenter, randomized, double-blind,
placebo-controlled studies in over 1400 patients 12 years of age or older with symptomatic moderate to severe persistent
asthma for at least 1 year and a positive skin test reaction to a perennial aeroallergen.a
Adult and Adolescent Patients 12 Years of Age and Older�The safety and efficacy of Xolair were evaluated in three randomized, double-blind, placebo-controlled, multicenter trials.�
The trials enrolled patients 12 to 76 years old, with moderate to severe persistent (NHLBI criteria) asthma for at least one
year, and a positive skin test reaction to a perennial aeroallergen. In all trials, Xolair dosing was based on body weight and
baseline serum total IgE concentration. All patients were required to have a baseline IgE between 30 and 700 IU/mL and
body weight not more than 150 kg. Patients 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.
In all three trials an exacerbation was defined as a worsening of asthma that required treatment with systemic
corticosteroids or a doubling of the baseline ICS dose. Most exacerbations were managed in the out-patient setting and the
majority was treated with systemic steroids. Hospitalization rates were not significantly different between Xolair and
placebo-treated patients; however, the overall hospitalization rate was small. Among those patients who experienced an
exacerbation, the distribution of exacerbation severity was similar between treatment groups.
Asthma Trials 1 and 2
At screening, patients in Asthma Trials 1 and 2 had a forced expiratory volume in one second (FEV1) between 40% and
80% predicted. All patients had a FEV1 improvement of at least 12% following beta2-agonist administration. All patients
were symptomatic and were being treated with inhaled corticosteroids (ICS) and short acting beta2-agonists. Patients
receiving other concomitant controller medications were excluded, and initiation of additional controller medications
while on study was prohibited. Patients currently smoking were excluded.
Each trial was comprised of a run-in period to achieve a stable conversion to a common ICS (beclomethasone
dipropionate), followed by randomization to Xolair or placebo. Patients received Xolair for 16 weeks with an unchanged
corticosteroid dose unless an acute exacerbation necessitated an increase. Patients then entered an ICS reduction phase of
12 weeks during which ICS dose reduction was attempted in a step-wise manner. The distribution of the number of
asthma exacerbations per patient in each group during a study was analyzed separately for the stable steroid and steroid-
reduction periods.
Page 14 of 20
In both Asthma Trials 1 and 2 the number of exacerbations per patient was reduced in patients treated with Xolair
compared with placebo.
Asthma Trial 3
In Asthma Trial 3, there was no restriction on screening FEV1, and unlike Asthma Trials 1 and 2, long-acting beta2-
agonists were allowed. Patients were receiving at least 1000 µg/day fluticasone propionate and a subset was also receiving
oral corticosteroids. Patients receiving other concomitant controller medications were excluded, and initiation of
additional controller medications while on study was prohibited. Patients currently smoking were excluded.
The trial was comprised of a run-in period to achieve a stable conversion to a common ICS (fluticasone propionate),
followed by randomization to Xolair or placebo. Patients were stratified by use of ICS-only or ICS with concomitant use
of oral steroids. Patients received Xolair for 16 weeks with an unchanged corticosteroid dose unless an acute exacerbation
necessitated an increase. Patients then entered an ICS reduction phase of 16 weeks during which ICS or oral steroid dose
reduction was attempted in a step-wise manner.
The number of exacerbations in patients treated with Xolair was similar to that in placebo-treated patients.
Summary
In these studies, patients stabilized on corticosteroid therapy (inhaled beclomethasone dipropionate in studies 1 and 2;
inhaled fluticasone propionate with or without oral corticosteroids in study 3) were randomized to receive either
subcutaneous omalizumab or placebo for 16 weeks (stable corticosteroid phase).a Dosage was based on body weight and
baseline serum total IgE concentration; patients received at least 0.016 mg/kg of omalizumab per IU of serum IgE
concentration (IgE/mL) every 4 weeks (maximum dosage: 750 mg every 4 weeks).a Patients then entered a corticosteroid
reduction phase for an additional 12 (studies 1 and 2) or 16 weeks (study 3) during which therapy with omalizumab or
placebo was continued while corticosteroid therapy was gradually tapered.a In 2 of the 3 studies (studies 1 and 2),
treatment with omalizumab was associated with a lower incidence of asthma exacerbations (defined as a worsening of
asthma that required treatment with systemic corticosteroids or a doubling of the baseline inhaled corticosteroid dosage)
compared with placebo; the incidence of asthma exacerbations was similar between omalizumab and placebo in study 3.a
Results:
‹ No reduction in the incidence of asthma exacerbations was observed in patients with a baseline forced expiratory
volume in 1 second (FEV1) exceeding 80% or in patients who required oral corticosteroids as maintenance therapy in
any of the studies.a
FDA expands use of Xolair (omalizumab) to children 6 to 11 years of age with moderate to severe persistent
asthma, [July 2016]a
The FDA expanded the indication to treat moderate to severe persistent asthma in children 6 to 11 years of age is
supported by multi-center, randomized, double-blind, placebo-controlled Phase III studies that assessed the efficacy and
safety of Xolair in children from six to 11 years old with moderate to severe persistent uncontrolled allergic asthma. The
primary study was a 52-week trial, with the primary endpoint measured at 24 weeks.a Supportive safety and efficacy data
come from a 28-week study4. Additional safety data come from a five-year non-randomized observational post-marketing
study to evaluate the long-term safety of Xolair in patients 12 years and older.6
The 52-week study evaluated the safety and efficacy of Xolair as an add-on therapy in children from six to 11 years old
with moderate to severe allergic asthma who was inadequately controlled despite the use of inhaled corticosteroids with or
without the use of other controller asthma medications. During the first 24 weeks of treatment, steroid doses remained
constant from baseline. This was followed by a 28-week period during which inhaled corticosteroid adjustment was
allowed. The primary efficacy variable in this study was the rate of asthma exacerbations during the 24-week, fixed
steroid treatment phase. An asthma exacerbation was defined as a worsening of asthma symptoms as judged clinically by
the investigator, requiring doubling of the baseline inhaled corticosteroid dose for at least three days and/or treatment with
rescue systemic corticosteroids for at least three days.a
Page 15 of 20
At 24 weeks, the Xolair treatment group had a statistically significantly lower rate of asthma exacerbations compared to
the placebo treatment group (0.45 vs. 0.64, respectively), representing a 31 percent relative rate reduction (rate ratio 0.69,
95 percent CI (0.53, 0.90) p=0.007)4. During the entire 52-week treatment period, the difference in asthma exacerbation
rates between the Xolair and placebo treatment groups (0.78 vs. 1.36, respectively) represented a 43 percent relative rate
reduction (rate ratio 0.57, 95 percent CI (0.45, 0.72) p<0.001).a
In clinical studies with pediatric patients six to 11 years old, the most common side effects (≥3 percent in Xolair-treated
patients and more frequent than placebo) were common cold symptoms (nasopharyngitis), headache, fever (pyrexia),