Omalizumab: An All-in-One Allergy Wonder Drug?

Since its initial FDA approval over 2 decades ago for moderate-to-severe asthma, omalizumab (Xolair; Genentech, Novartis), a recombinant humanized monoclonal anti-immunoglobulin E (IgE) antibody, has continued to demonstrate efficacy across a growing spectrum of IgE–mediated disease. Beyond asthma, omalizumab is FDA approved for treatment of chronic rhinosinusitis with nasal polyps (CRSwNP) and chronic spontaneous urticiaria (CSU). Most recently, its clinical utility has expanded into food allergies as the first and only therapy approved to manage a condition that historically has had limited pharmacological options.¹

Although omalizumab is not currently FDA-approved for allergic rhinitis (AR), emerging data support omalizumab’s potential to address both seasonal and perennial forms of the disease. The growing use of omalizumab in allergic disorders has led to interest in omalizumab as a possible “all-in-one” allergy relief solution.

Clinical Considerations

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Omalizumab is a recombinant monoclonal antibody that selectively binds to circulating IgE and reduces free IgE levels, which in turn downregulates high-affinity IgE receptors, limits mast cell degranulation, and minimizes the release of mediators throughout the allergic inflammatory cascade. It is administered as a subcutaneous injection every 2 to 4 weeks based on IgE level, patient weight, and indication. It is typically administered by a health care provider in a clinic or at home but can also be self-administered by patients and their caregivers if deemed appropriate by the care team.

Although omalizumab is generally well-tolerated, clinicians should counsel patients regarding the risk of injection site reactions, arthralgia, headache, and rare but serious hypersensitivity events, including anaphylaxis. Postmarketing surveillance supports a favorable safety profile, though precautions remain essential, particularly during initial doses.¹

FDA Approval for Food Allergy

Food allergy poses a significant global health burden, affecting approximately 3.4 million children and 13.6 million adults in the US alone. Reactions range from hives and swelling to life-threatening anaphylaxis. An estimated 30,000 food-related anaphylaxis events lead to emergency room visits in the US each year. Dietary avoidance and oral immunotherapy (OIT) have been the primary means of management, but come with significant social, nutritional, and financial burdens.^2-4

In February 2024, the FDA approved Xolair for the reduction of allergic reactions, including anaphylaxis, following accidental exposure to food allergens in individuals aged 1 year or older with a confirmed IgE-mediated food allergy. This approval was supported by results from Stage 1 of the National Institutes of Health–sponsored OUtMATCH phase 3 trial. In this randomized, placebo-controlled trial, participants with documented peanut allergy and at least 2 additional food allergies achieved statistically significant increases in tolerated food allergen doses after omalizumab treatment.^5-7

Stage 2 of the OUtMATCH study showed Xolair was more effective with fewer adverse effects than multi-allergen OIT in the first-ever head-to-head trial comparing the 2 treatment approaches. These data offer compelling evidence for omalizumab as a monotherapeutic alternative to OIT, which has been limited by poor tolerability and adherence. Stage 3 of this study examining introduction of allergenic foods into a patient’s diet after stopping omalizumab is ongoing.^5-7

Beyond omalizumab, several other biologic therapies for food allergy are under active investigation. One promising agent is dupilumab (Dupixent; Sanofi, Regeneron), an IL-4 and IL-13 inhibitor currently approved for asthma, atopic dermatitis, and eosinophilic esophagitis. Regeneron and Sanofi have initiated a phase 1 trial evaluating dupilumab in combination with linvoseltamab, a bispecific antibody, for severe food allergy.⁸

Emerging Evidence in Allergic Rhinitis

Although omalizumab is not currently approved by the FDA for the treatment of AR, a growing body of literature suggests potential clinical benefit, particularly in patients with moderate-to-severe or treatment-refractory disease. Globally, AR affects an estimated 10% to 30% of the population, and its prevalence continues to rise in industrialized nations. The American Academy of Allergy, Asthma, and Immunology attributes this trend to increased urbanization, environmental exposures, and heightened allergen sensitivity. In the United States alone, the economic burden of allergic rhinitis has been estimated to exceed $4.6 billion annually in direct treatment costs.^9,10

By targeting IgE, omalizumab can prevent the allergic response at its source, offering relief with just 1 injection before allergy season. Unlike traditional antihistamines or intranasal corticosteroids that treat downstream symptoms, omalizumab addresses the immunologic trigger of allergic inflammation. Several studies have demonstrated efficacy of omalizumab in reducing allergic rhinitis symptoms.¹¹

A 2022 randomized, double-blind, placebo-controlled trial demonstrated that a single 300 mg dose of omalizumab administered prior to pollen season significantly improved symptom severity scores and reduced antihistamine use in patients with seasonal AR sensitized to spring allergens.¹¹ Similarly, a retrospective cohort analysis found that patients treated with omalizumab during peak pollen seasons experienced reduced reliance on rescue medications and improved overall symptom burden compared to matched controls.¹² Longitudinal studies have also reported benefits in perennial AR, particularly among patients with persistent symptoms unresponsive to standard therapies.^13-15 These findings suggest omalizumab may offer an important adjunct or alternative in refractory cases.

However, cost remains a critical consideration. Despite its clinical potential, omalizumab remains among the most expensive therapies within allergy and immunology, with a US wholesale acquisition cost ranging from $30,000 to $60,000 annually.¹⁶ This high cost challenges formulary placement, reimbursement decisions, and equitable access, particularly for patients with non-life-threatening, quality-of-life limiting conditions such as AR.

Biosimilars Approval

In March 2025, the FDA approved Omlyclo (omalizumab-igec; Celltrion) as the first interchangeable biosimilar to Xolair. This designation, which allows for substitution at the pharmacy level (subject to state regulations), was based on a head-to-head trial in 619 patients with chronic spontaneous urticaria (CSU).¹⁷ The study demonstrated bioequivalence in pharmacokinetics, immunogenicity, and clinical outcomes. Omlyclo’s approval may improve access to omalizumab therapy through cost containment and formulary expansion.¹⁷ Several other biosimilars are in the pipeline, including products from Amneal, Teva, and Kashiv Biosciences.¹⁸

The recent FDA approval of Omlyclo and the expanded indications for omalizumab, most notably its 2024 approval for IgE-mediated food allergy, represent major milestones in the management of allergic conditions. With over 850,000 US patients exposed to omalizumab since its launch, its safety and efficacy profile is well established across multiple indications, including asthma, CSU, and now food allergy.¹⁹ The high annual price tag continues to pose significant barriers to equitable access. Availability of Omlyclo may help shift this dynamic as it has the potential to introduce market competition that can drive down costs and expand access. Yet, the real-world impact of biosimilars of biologic pricing has been historically modest, with uptake lag due to rebates, prescriber familiarity, and formulary exclusivities.¹⁸ Nevertheless, omalizumab’s robust efficacy, safety, and broad indication coverage highlights its potential as a unique solution for allergic disease management.

REFERENCES

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7. Wood RA, Chinthrajah RS, Spergel AKR, et al. Protocol design and synopsis: omalizumab as monotherapy and as adjunct therapy to multiallergen OIT in children and adults with food allergy (OUtMATCH). J Allergy Clin Immunol Glob. 2022;1(4):225-232. doi:10.1016/j.jacig.2022.05.006

8. Short-Term Linvoseltamab Treatment on Top of Chronic Dupilumab Treatment for Adults With Severe Immunoglobulin E (IgE)-Mediated Food Allergy. Regeneron. Accessed May 15, 2025. https://clinicaltrials.regeneron.com/clinical-trials/a0MPr0000006GRuMAM/nct06369467

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14. Yu C, Wang K, Cui X, et al. Clinical efficacy and safety of omalizumab in the treatment of allergic rhinitis: a systematic review and meta-analysis of randomized clinical trials. Am J Rhinol Allergy. 2020;34(2):196-208. doi:10.1177/1945892419884774

15. Cavaliere C, Begvarfaj E, Incorvaia C, et al. Long-term omalizumab efficacy in allergic rhinitis. Immunol Lett. 2020;227:81-87. doi:10.1016/j.imlet.2020.08.002

16. Xolair Pricing and Financial Support. Accessed May 15, 2025. https://www.xolair.com/cost.html

17. Saini SS, Maurer M, Dytyatkovska Y, et al. CT-P39 compared with reference omalizumab in chronic spontaneous urticaria: results from a double-blind, randomized, active-controlled, phase 3 study. Allergy. 2024;0:1-11. doi:10.1111/all.16556

18. Jeremias S. Biosimilars Account for 23% Market Share, With Wide Uptake Disparities Across Molecules. Center for Biosimilars. May 22, 2024. Accessed May 15, 2025. https://www.centerforbiosimilars.com/view/biosimilars-account-for-23-market-share-with-wide-uptake-disparities-across-molecules

19. Phase III study shows Xolair may be more effective with fewer side effects than oral immunotherapy for the treatment of food allergies. News release. Roche. March 2, 2025. Accessed May 15, 2025. https://www.globenewswire.com/news-release/2025/03/02/3035199/0/en/Phase-III-study-shows-Xolair-may-be-more-effective-with-fewer-side-effects-than-oral-immunotherapy-for-the-treatment-of-food-allergies.html