Xolair Outperforms Oral Immunotherapy in Landmark Phase III OUtMATCH Food Allergy Trial
Xolair (omalizumab) shows superior efficacy and safety compared to multi-allergen oral immunotherapy in treating food allergies in the Phase III OUtMATCH trial, suggesting the potential to facilitate the introduction of allergenic foods into patients' diets after treatment.
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Xolair (omalizumab) demonstrated superior efficacy and safety compared to multi-allergen oral immunotherapy in treating food allergies, according to results of the Phase III OUtMATCH trial (NCT03881696).1,2 Findings from the trial, which was the first head-to-head study evaluating these two treatment approaches for food allergy, suggest the potential to facilitate the introduction of allergenic foods to patients’ diets after treatment with Xolair, according to investigators.
“Food allergies are becoming more common, leaving millions of families to grapple with constant vigilance, strict dietary restrictions and disruptions to everyday activities,” OUtMATCH co-lead study investigator R. Sharon Chinthrajah, MD, associate professor of medicine, Stanford School of Medicine, Sean N. Parker Center for Allergy and Asthma Research, said in a press release. “These findings equip healthcare providers with valuable data on [Xolair] and oral immunotherapy, enabling them to continue to address the diverse needs and treatment goals of their food allergy patients.”1
Xolair is a monoclonal antibody that binds to and inhibits immunoglobulin E (IgE), which is involved in the pathophysiology of the allergic inflammation characteristic of asthma.2 Through this mechanism of action, IgE down-regulates the immune response to help control allergy-driven inflammation.3
In February, the FDA approved an expanded indication for Xolair to reduce allergic reactions from exposure to one or more food allergens in individuals over 1 year of age with IgE-mediated food allergy.4 The FDA previously granted Xolair with Breakthrough Therapy Designation in August 2018 to prevent severe allergic reactions after accidental exposure to one or more foods in patients with allergies. Xolair is also approved to treat moderate to severe persistent allergic asthma, chronic spontaneous urticaria, and chronic rhinosinusitis with nasal polyps.
Trial Design
The National Institutes of Health-sponsored multicenter, randomized, double-blind, placebo-controlled pivotal OUtMATCH trial analyzed Xolair in patients allergic to peanuts and at least two other common foods. The trial included patients from 1 to 55 years of age with a peanut allergy and at least two other food allergies, such as milk, egg, wheat, cashew, hazelnut, and walnut allergies.
Stage one of the trial included 180 patients randomly assigned to receive placebo or Xolair injections every two weeks or every four weeks for a duration of 16 to 20 weeks. After this point, patients participated in blinded food challenges in a carefully controlled setting.
Xolair achieved the trial’s primary endpoint, with 36% of patients administered Xolair monotherapy able to tolerate at least 2,000 mg of peanut protein along with two other food allergens without developing an allergic reaction vs. 19% of patients in the oral immunotherapy cohort (odds ratio=2.6, P=0.031).
A total of 117 patients advanced to stage two of the trial, in which they were administered eight weeks of open-label Xolair before being randomly assigned to receive multi-allergen oral immunotherapy or placebo oral immunotherapy along with Xolair for an additional eight weeks. After this period, patients in the oral immunotherapy cohort switched over to placebo for an additional 44 weeks, with the other cohort remaining on Xolair with placebo oral immunotherapy.
At this point, patients had another series of blinded food challenges with the three study-specific foods of peanut and two other foods from the group of milk, egg, wheat, cashew, hazelnut, and/or walnut.
The superiority of Xolair was shown across multiple secondary endpoints, including the ability to tolerate two or more foods (P=0.004). Investigators reported high rates of adverse events (AEs) among patients in the oral immunotherapy cohort.
Serious AEs were reported by 30.5% of patients in the oral immunotherapy cohort compared to 0% in the Xolair cohort. AEs causing treatment discontinuation occurred in 22% of patients in the oral immunotherapy cohort compared to 0% in the Xolair cohort and AEs requiring epinephrine treatment occurred in 37.3% of patients in the oral immunotherapy cohort compared to 6.9% in the Xolair cohort.
The first 60 patients who completed stage one of the trial were enrolled in a 24-week open-label extension followed by stage three, which involved consuming allergenic foods, rescue oral immunotherapy, or food avoidance based on results from the final food challenge and patient preferences. During this time, patients were no longer administered Xolair.
Each patient was given a treatment plan for each of the three food allergens from the trial. Among 180 treatment plans, 82% included consuming allergenic foods. After 12 months of follow-up, a high number of patients were able to include their allergenic foods in dietary form. Success rates were found to be higher for milk, egg, and wheat allergies, at a range of 61%-70% compared to peanuts and tree nuts at a rate of 38%-56%.
Decreased consumption of allergenic foods was apparently related to symptoms and other factors, with investigators reporting unclear predictors of success. Many patients returned to avoiding these foods because of AEs and additional factors, with AEs including anaphylaxis and epinephrine use.
“These latest data provide additional evidence demonstrating the importance of Xolair as a treatment option for the food allergy community,” Levi Garraway, MD, PhD, Roche chief medical officer and head of Global Product Development, said in the release. “We are deeply grateful to the leading research institutions who partnered with us on this groundbreaking study, along with the inspiring dedication of the study’s participants and their families.”1
References
1. 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 1, 2025. Accessed March 3, 2025. https://www.roche.com/media/releases/med-cor-2025-03-02
2. Omalizumab as Monotherapy and as Adjunct Therapy to Multi-Allergen OIT in Food Allergic Participants (OUtMATCH). ClinicalTrials.gov. Updated January 28, 2025. Accessed March 3, 2025. https://clinicaltrials.gov/study/NCT03881696?term=NCT03881696&rank=1
3. FDA Grants Priority Review to Xolair (omalizumab) for Children and Adults With Food Allergies Based on Positive National Institutes of Health Phase III Study Results. Genentech. News release. December 19, 2023. Accessed March 3, 2025. https://www.gene.com/media/press-releases/15016/2023-12-19/fda-grants-priority-review-to-xolair-oma
4. FDA approves Xolair® (omalizumab) as first and only medicine for children and adults with one or more food allergies. Novartis. News release. February 16, 2024. Accessed March 3, 2025. https://www.novartis.com/us-en/news/media-releases/fda-approves-xolair-omalizumab-first-and-only-medicine-children-and-adults-one-or-more-food-allergies#:~:text=EAST%20HANOVER%2C%20N.J.%2C%20Feb.,patients%20aged%201%20year%20and
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