Xolair for the Treatment of IgE-Mediated Food Allergies

In February 2024, the US Food and Drug Administration (FDA) approved Xolair (omalizumab; Genentech, Inc), an anti-immunoglobulin E (IgE) antibody, for the treatment of IgE-mediated food allergies in patients aged 1 year and older for the reduction of type 1 allergic reactions, including anaphylaxis, that may occur with accidental exposure to 1 or more foods. The treatment should be used in conjunction with food allergen avoidance.

Xolair should not be used for the treatment of emergency allergic reactions, including anaphylaxis. 

Omalizumab works by inhibiting the binding of IgE to the high-affinity IgE receptor (FcεRI) on mast cell, basophil, and dendritic cell surfaces. This results in FcεRI down-regulation on these cells. 

Additional indications for Xolair include treatment of asthma, chronic rhinosinusitis with nasal polyps, and chronic spontaneous urticaria.

Clinical Trials

The approval of Xolair for food allergies was based on results obtained from the food allergy (FA) trial (ClinicalTrials.gov identifier: NCT03881696). The multicenter study was a randomized, double-blind, and placebo-controlled clinical trial that included patients allergic to peanut and at least 2 other foods (milk, egg, wheat, cashew, hazelnut, or walnut).

A total of 168 adult and pediatric patients aged 1 to less than 56 years were enrolled in the trial. During the screening double-blind, placebo-controlled food challenge (DBPCFC), eligible participants experienced dose-limiting symptoms to a single dose of ≤100 mg of peanut protein and ≤300 mg protein for each of the other 2 foods. Dose-limiting symptoms included moderate to severe skin reactions, respiratory symptoms, or gastrointestinal symptoms. Patients were excluded from the study if they had a history of severe anaphylaxis, defined as neurological compromise or requiring intubation. 

Study participants were randomly assigned  (2:1) to receive either Xolair subcutaneously or placebo for 16 to 20 weeks. The dose of Xolair was calculated based on the patient’s body weight and baseline serum total IgE level (IU/mL). Following the 16- to 20-week study period, each patient underwent a DBPCFC consisting of placebo and each of their 3 studied foods. After the DBPCFC, the first 60 patients (59 pediatric patients, 1 adult patient) continued to receive Xolair in a 24- to 28-week open-label extension study. 

The efficacy analyses included 165 pediatric patients (Figure 1). 

The primary efficacy outcome was the percentage of patients able to consume 1 dose of ≥600 mg of peanut protein without experiencing dose-limiting symptoms during DBPCFC. Secondary outcomes of the study included the percentage of patients able to consume 1 dose of ≥1000 mg of cashew, milk, or egg protein without experiencing dose-limiting symptoms during DBPCFC.

Findings revealed treatment with Xolair resulted in statistically higher response rates for the primary and secondary endpoints compared with placebo (Figure 2). 

Findings also revealed that 17% of patients receiving Xolair were not able to have >100 mg of peanut protein without experiencing moderate to severe dose-limiting symptoms. Additionally, 18%, 22%, and 41% of patients treated with Xolair were not able to consume >300 mg of milk, egg, and cashew protein, respectively, without dose-limiting symptoms. 

Secondary analyses also assessed the percentage of patients able to consume at least 2 or all 3 foods during DBPCFC. When analyzing 2 foods, 71% of Xolair-treated patients were able to consume a single dose of ≥600 mg compared with 5% of patients who received placebo. This analysis also showed 67% of patients in the Xolair group were able to consume a single dose of ≥1000 mg of 2 foods vs 4% of patients in the placebo group. 

Findings also showed that 48% and 39% of Xolair patients were able to consume ≥600 mg and ≥1000 mg of 3 foods without symptoms, respectively, compared with 4% and 0% of placebo patients. 

Xolair effectiveness is supported for adult patients by the results obtained through adequate trials completed in pediatric patients and the similarities of the disease and pharmacokinetic profiles between these populations. 

For the 38 pediatric patients who continued to receive Xolair for the 24- to 28-week open-label extension study, findings showed that the percentage of patients able to tolerate ≥600 mg of peanut protein and ≥1000 mg egg, milk, and/or cashew protein was maintained without dose-limiting symptoms.

Dosage and Administration

Xolair is supplied as a prefilled syringe, an autoinjector, and as a lyophilized powder for single-use. Both the prefilled syringe and the autoinjector come in the following strengths: 75 mg/0.5 mL, 150 mg/mL, and 300 mg/2 mL. The lyophilized powder is dispensed as 150 mg for injection in a single-dose vial for reconstitution. 

The recommended dosage of Xolair for the treatment of IgE-mediated FA is 75 mg to 600 mg by subcutaneous injection every 4 weeks (Table 1) or every 2 weeks (Table 2) based on a patient’s serum total IgE level (IU/mL) at the start of treatment and body weight (kg). The dose of Xolair must be adjusted if  significant changes in body weight occur during treatment. As the appropriate duration of therapy for IgE-mediated FA has not been evaluated, periodic reassessment is recommended to see if continued therapy is needed.

Do not retest IgE levels during treatment with Xolair as a guide for determining a patient’s dose. IgE levels will be elevated during treatment with Xolair as well as for up to 1 year following discontinuation of the medication. For interruptions in therapy lasting less than a year, base the dose on the serum IgE level obtained at the initial dose determination. For interruptions lasting 1 year or more, retest serum IgE levels to determine a patient’s dose of Xolair. 

At the beginning of treatment, the prefilled syringe and autoinjector forms of Xolair must be given under the supervision of a healthcare provider. Once safety has been established, Xolair can be self-administered by the patient or a caregiver at home. The Xolair lyophilized powder formulation must be prepared and administered by a healthcare provider only. 

When selecting patients for self-administration of Xolair, certain factors should be considered (Table 3).

Intructions For Prefilled Syringe and Autoinjector Use

• Xolair prefilled syringes should not be handled by patients and caregivers with latex allergies. 
• Determine the number of prefilled syringes or autoinjectors required for a patient’s dose.
• Subcutaneously administer Xolair into the thigh or abdomen.
  • Avoid the 2-inch area directly around the navel.
  • Outer area of the upper arms may be used only if Xolair is being given by a caregiver or healthcare provider.
  • If more than 1 injection is required to complete a full dose, administer each injection at least 1 inch apart from other injection sites.

Instructions For Xolair Lyophilized Powder

• Determine the number of vials required for a patient’s dose.
• Inject 1.4 mL of Sterile Water for Injection (SWFI) USP into the lyophilized powder vial and swirl for approximately 1 minute.
  • Continue to swirl for 5 to 10 seconds every 5 minutes to dissolve the product.
  • It should take 15 to 20 minutes for the product to completely dissolve.
  • Use the Xolair solution within 8 hours after reconstitution when stored in the vial between 36°F and 46°F or within 4 hours of reconstitution when stored at room temperature.  
• Withdraw all of the product using a 3 mL syringe equipped with a 1-inch, 18-gauge needle.
  • Replace 18-gauge needle with a 25-gauge needle for subcutaneous injection.
• Administer 1.2 mL of solution (corresponding to a 150-mg Xolair dose) or 0.6 mL of solution (corresponding to a 75-mg dose).
  • Do not inject more than 150 mg (1 vial) per injection site; divide doses >150 mg between 2 or more injection sites at least 1 inch apart.

Contraindications, Warnings, Precautions, and Adverse Reactions

Xolair is contraindicated in patients with a hypersensitivity to Xolair or any of its components.

Anaphylaxis

Cases of anaphylaxis, including life-threatening events, have occurred in patients receiving Xolair. Signs and symptoms of anaphylaxis include bronchospasm, hypotension, syncope, urticaria, and/or angioedema of the tongue or throat.

During premarketing clinical trials, anaphylaxis was reported in 0.1% (3/3507) of patients with asthma. Of these 3 patients, 2 experienced anaphylaxis with their first dose of Xolair and 1 experienced it with their fourth dose. In 2 patients, the onset of anaphylaxis was reported to be 90 minutes following administration while 1 patient experienced anaphylaxis 2 hours after receiving Xolair.

A case-control study revealed that compared with patients with no prior anaphylaxis history, patients with a history of anaphylaxis to foods, medications, or other agents had an increased risk of anaphylaxis associated with Xolair use.

Postmarketing spontaneous reports estimated the frequency of anaphylaxis associated with Xolair use to be at least 0.2% of patients based on an estimated exposure of 57,300 patients between June 2003 and December 2006. It was also reported that anaphylaxis occurred between the first dose of treatment through 1 year after receiving Xolair regularly. It is estimated that about 60% to 70% of cases of anaphylaxis occur within the first 3 doses of Xolair. 

Xolair should only be initiated in a healthcare setting equipped to manage anaphylaxis. Patients should be monitored for an appropriate time period following Xolair administration. Patients should also be counseled on the signs and symptoms of anaphylaxis and should be informed to seek medical care immediately if they experience any signs or symptoms of this life-threatening condition. 

Select patients may be qualified for self-administration of the Xolair prefilled syringe or autoinjector outside of a healthcare setting once Xolair therapy has been established. Xolair should be discontinued in patients who experience a severe hypersensitivity reaction.

Malignancy

In clinical studies including adults and adolescents ≥12 years of age who have asthma and other allergic disorders, malignant neoplasms were reported in 0.5% (20/4127) of patients. A variety of types of malignancies were observed in varying frequencies: breast, nonmelanoma skin, prostate, melanoma, and parotid occurred at least once; 5 other types occurred 1 time each. Most patients were observed for less than 1 year. It is unknown whether longer Xolair exposure or a higher risk of malignancy impacts the risk of malignancy in these patients. 

In a subsequent observational study, the incidence rates of primary malignancies were found to be similar among Xolair-treated and non-Xolair-treated patients. However,  malignancy risk with Xolair could not be ruled out as the study had several limitations.

Fever, Arthralgia, and Rash

A constellation of signs and symptoms, including arthritis/arthralgia, rash, fever, and lymphadenopathy, may occur with Xolair use. The onset of these symptoms typically occurs 1 to 5 days following Xolair administration. These signs and symptoms may recur following subsequent Xolair injections and are similar to those observed in patients with serum sickness. Xolair should be discontinued in patients who develop these signs and symptoms. 

Parasitic (Helminth) Infection

Patients at high risk for geohelminth infection should be monitored while receiving Xolair therapy. There are insufficient data on the exact length of monitoring required for geohelminth infections following Xolair discontinuation. 

A 1-year clinical study conducted in Brazil revealed that 53% (36/68) of Xolair-treated patients who were considered high risk for geohelminthic infections were diagnosed with an infection compared with 42% (29/69) of placebo patients.  The point estimate of the odds ratio for infection was reported to be 1.96 (95% CI, 0.88-4.36). This indicates that a patient with an infection was between 0.88 and 4.36 times as likely to have received Xolair vs a patient who did not have an infection. No difference was observed between treatment groups when analyzing response to appropriate anti-geohelminth therapy for infection, which is measured by stool egg counts. 

Laboratory Tests

Due to the formation of Xolair:IgE complexes, an increase in serum total IgE levels will be observed following Xolair administration. This elevation may persist for up to 1 year after Xolair discontinuation. Since these levels are not reflective of steady-state free IgE levels, serum total IgE levels obtained less than 1 year after Xolair discontinuation should not be used to reassess the dosing regimen for Xolair.

Potential Medication Error Related to Emergency Treatment of Anaphylaxis

Xolair is not indicated for emergency treatment of allergic reactions, including anaphylaxis. According to studies simulating use, a number of patients and caregivers did not understand that Xolair should not be used to treat allergic reactions. The safety and effectiveness of Xolair have not been established to treat emergency allergic reactions. It is important to counsel patients and caregivers that Xolair is intended to be used as maintenance treatment to reduce allergic reaction to food allergens.

Adverse Reactions

The safety of Xolair was assessed in the FA trial, including 168 patients (165 pediatric and 3 adult patients) with type 1 IgE-mediated allergic reactions to peanuts and at least 2 other foods. 

During the study, patients randomly received Xolair or placebo subcutaneously every 2 or 4 weeks for 16 to 20 weeks. A patient’s dose was dependent on their baseline total IgE level (IU/mL) and body weight (kg).

Safety findings obtained from the primary analysis population (pediatric patients aged 1 to 17 years old) revealed that 15.5% (17/110) of Xolair-treated patients experienced injection-site reactions and 6.4% (7/110) experienced pyrexia. Comparatively, 10.9% (6/55) and 3.6% (2/55) of placebo patients experienced injection-site reactions and pyrexia, respectively.

Drug Interactions

No drug interaction studies for Xolair have been conducted at this time. Concomitant use of Xolair with allergen immunotherapy has also not been evaluated at this time.

Considerations for Specific Populations

No increase in major birth defects or miscarriage was observed in a registry study including 250 pregnant women with asthma, 246 of whom were exposed to Xolair during pregnancy. An increased risk of low birth weight was seen in registry infants (13.7%) compared with those in other cohorts (9.8%), regardless of average gestational age at birth. It was noted, however, that it was difficult to determine if this low birth weight was caused by Xolair or disease severity since women taking Xolair during pregnancy had more severe asthma. Poorly or moderately controlled asthma during pregnancy is known to cause problems after pregnancy. 

Xolair may be transmitted to the developing fetus from the mother since human IgG antibodies are known to cross the placental barrier. 

No data currently exist on the presence of Xolair in breast milk or its effect on milk production. It is known, however,  that IgG is present in breast milk. 

Based on data obtained from the registry exposure study, infants exposed to Xolair did not have a significantly increased risk for “infections and infestations” events compared with infants not breastfed or exposed to Xolair. During the study, 80.9% (186/230) of infants were breastfed. The benefits of breastfeeding, a mother’s clinical need for Xolair, and the potential adverse effects of Xolair on the breastfed child should be considered.

The efficacy and safety of Xolair have been established in pediatric patients aged 1 year and older who have an IgE-mediated FA. This study included 165 pediatric patients, including 61 patients aged 1 to less than 6 years of age and 104 patients aged 6 to less than 18 years of age. Study findings revealed that a significantly greater percentage of patients treated with Xolair were able to consume a single dose of food without dose-limiting symptoms compared with patients who received placebo. The safety and effectiveness of Xolair have not been established in pediatric patients less than 1 year of age. 

The FA study did not include patients aged 65 years or older; therefore, it is unclear if these patients would respond differently from younger patients. 

Reference

Xolair^®. Prescribing information. Genentech, Inc; 2024. Accessed February 26, 2024. https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/103976s5245lbl.pdf.

Posted by Haymarket’s Clinical Content Hub. The editorial staff of MPR had no role in this content’s preparation.

Reviewed March 2024