Omalizumab Injection (Xolair)

By William Elliott, MD, FACP, and James Chan, PharmD, PhD

Dr. Elliott is Assistant Clinical Professor of Medicine, University of California, San Francisco.

Dr. Chan is Associate Clinical Professor, School of Pharmacy, University of California, San Francisco.

The U.S. Food and Drug Administration (FDA) has approved the first medication to help reduce allergic reactions, including anaphylaxis, that may occur after accidental exposure to multiple foods.¹ Omalizumab is a recombinant humanized IgG1k monoclonal antibody that selectively binds to immunoglobulin E (IgE) lowering free serum IgE levels.² Currently, it is approved for the treatment of moderate to severe persistent asthma, chronic rhinosinusitis with nasal polyps, and chronic spontaneous urticaria. The new indication was given an accelerated priority review and fast-track-breakthrough therapy designation.¹ Omalizumab injection is distributed by Genentech as Xolair.

INDICATIONS

Omalizumab is indicated for 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.² It is to be used in conjunction with food allergy avoidance.

DOSAGE

The dose and frequency of omalizumab is determined by body weight and the serum total IgE level measured before the start of treatment.² The range is 75 mg to 600 mg given subcutaneously every two to four weeks. Omalizumab is available as 75 mg/0.5 mL, 150 mg/mL, and 300 mg/mL as single-dose prefilled syringes or autoinjectors.²

POTENTIAL ADVANTAGES

Omalizumab is the first medication approved by the FDA for the reduction of allergic reactions due to accidental exposure to foods.¹

POTENTIAL DISADVANTAGES

Omalizumab appears to be less effective in cashew allergy.² Treatment requires chronic administration (i.e., every two to four weeks) and has significant associated cost (as high as $144,040 per year). Anaphylaxis, presenting as bronchospasm, hypotension, syncope, urticaria, and/or angioedema of the throat or tongue, have been reported.^2,3 The drug should be initiated in a healthcare setting where the patient should be monitored for an appropriate period of time after administration. Selection of patients for self-administration should be based on criteria to mitigate risk from anaphylaxis.

COMMENTS

The safety and efficacy of omalizumab was evaluated in a randomized, double-blind, placebo-controlled trial (n = 165).^2,3 Participants were allergic to peanuts and at least two other foods, including milk, egg, wheat, cashew, hazelnut, or walnut. Eligible participants experienced dose-limiting symptoms (e.g., moderate to severe skin, respiratory, or gastrointestinal symptoms) to a single dose ≤ 100 mg peanut protein and ≤ 300 mg protein for each of the other two foods. Those with a history of severe anaphylaxis (neurologically compromised or requiring intubation) were excluded. Participants were randomized to omalizumab or placebo (2:1) for 16 to 20 weeks.
The primary efficacy endpoint was the percentage of participants who were able to consume a single dose ≥ 600 mg peanut protein without dose-limiting symptoms during a double-blind, placebo-controlled food challenge. The response rates for omalizumab (vs. placebo) for the food challenge dose were peanut ≥ 600 mg, 68% vs. 5%; peanut ≥ 1,000 mg, 65% vs. 0%; cashew ≥ 1,000 mg, 42% vs. 3%; milk ≥ 1,000 mg, 66% vs. 11%; and egg ≥ 1,000 mg, 67% vs. 0%. Forty-eight percent of participants (vs. 4%) were able to tolerate a single dose (≥ 600 mg) of three foods. Seventeen percent of omalizumab treated participants were not able to tolerate > 100 mg of peanut without moderate to severe dose-limiting symptoms.² Eighteen percent, 22%, and 41% of treated participants did not tolerate > 300 g of milk, egg, or cashew protein respectively.²

CLINICAL IMPLICATIONS

Food allergy is a chronic disease characterized by an IgE-mediated response to a dietary protein.⁴ It is the leading cause of severe and fatal allergic reactions. The estimated prevalence in U.S. adults is 6.2% and in children is 5.8%.⁵ Black, non-Hispanic children and adults are more likely to have a food allergy compared to other races.⁵ Management of food allergy involves avoidance and, in the event of accidental ingestion, epinephrine autoinjector. Recently, peanut allergen powder (Palforzia) was approved as oral immunotherapy (OIT) for desensitizing peanut allergy in children (4-17 years of age), but it is limited to peanut allergy.^1,6,7 Omalizumab provides another option that significantly increased the tolerated dose of allergic food as monotherapy and as adjunct to OIT.^8,9 Omalizumab may be able to enhance oral desensitization in peanut-allergy patients at high risk for developing significant reaction to even small amounts of exposure.⁸ The annual cost for omalizumab ranges from $8,996 to $144,040, depending on body weight and pretreatment serum IgE level.

REFERENCES

1. U.S. Food and Drug Administration. FDA approves first medication to help reduce allergic reactions to multiple foods after accidental exposure. https://www.fda.gov/news-events/press-announcements/fda-approves-first-medication-help-reduce-allergic-reactions-multiple-foods-after-accidental
2. Xolair prescribing information. Genentech, Inc. February 2024. https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/103976s5238lbl.pdf
3. ClinicalTrials.gov. Omalizumab as monotherapy and as an adjunct therapy to multi-allergen OIT in food allergic participants (OUtMATCH). https://clinicaltrials.gov/study/NCT03881696
4. Mahdavinia M. Food allergy in adults: Presentations, evaluation, and treatment. Med Clin North Am 2020;104:145-155.
5. Centers for Disease Control and Prevention. More than a quarter of U.S. adults and children have at least one allergy. Jan. 26, 2023. https://www.cdc.gov/nchs/pressroom/nchs_press_releases/2022/20220126.htm
6. Palforzia prescribing information. Aimmune Therapeutics, Inc. March 2023. https://www.fda.gov/media/134838/download
7. PALISADE Group of Clinical Investigators; Vickery BP, Vereda A, Casale TB, et al. AR101 oral immunotherapy for peanut allergy. N Engl J Med 2018;379:1991-2001.
8. Zuberbier T, Wood RA, Bindslev-Jensen C, et al. Omalizumab in IgE-mediated food allergy: A systematic review and meta-analysis. J Allergy Clin Immunol Pract 2023;11:1134-1146.
9. Flocchi A, Vickery BP, Wood RA. The use of biologics in food allergy. Clin Exp Allergy 2021;51:1006-1018.