Omalizumab remains superior to oral immunotherapy (OIT) for the treatment of multi-food allergies with fewer adverse effects in Stage 2 of the NIH*-sponsored phase III OUtMATCH** study, the first head-to-head trial comparing the two treatments.

A total of 117 patients (55 percent male, median age 7 years) from OUtMATCH Stage 1 moved on to Stage 2, wherein all participants received open-label omalizumab for 8 weeks. They were then randomized to multi-allergen or placebo OIT while continuing omalizumab for another 8 weeks. Following which, participants on OIT switched to placebo for 44 more weeks while those on omalizumab continued their treatment. [AAAAI/WAO 2025, abstract L48]

After the treatment phase, patients were rechallenged with their three study-specific foods (peanut and two other foods from egg, milk, wheat, cashew, hazelnut, and/or walnut). About 90 percent of participants in the omalizumab arm completed stage 2; in the OIT arm, the corresponding percentage was 51 percent.

The study met its primary endpoint, with over a third of omalizumab recipients being able to tolerate ≥2,000 mg of peanut protein and two other food allergens without having an allergic reaction, as opposed to 19 percent with the comparator (odds ratio, 2.6; p=0.031).

Superiority was also shown for several secondary endpoints, including tolerating ≥2 foods (p=0.004).

According to the investigators, the results were primarily driven by the higher rate of adverse events (AEs) leading to study discontinuation in the OIT vs omalizumab arm despite the administration of omalizumab at the beginning of therapy (22 percent vs 0 percent). The former group also had higher rates of serious AEs (30.5 percent vs 0 percent) and AEs treated with epinephrine (37.3 percent vs 6.9 percent) than the latter.

Stage 3 initial results

Preliminary findings from OUtMATCH Stage 3 provide early data on the introduction of allergenic foods into a patient’s diet after stopping omalizumab treatment.

The first 60 participants (58 percent male, median age 8.5 years) who completed OUtMATCH Stage 1 entered the 24-week open-label omalizumab extension, followed by stage 3 (off omalizumab). Stage 3 could include dietary consumption, rescue OIT, or food avoidance, depending upon the results of the final food challenge and patient preferences. [AAAAI/WAO 2025, abstract L50]

Each participant received a treatment plan for each of their three allergens. Of the 180 plans, 148 (82 percent) included dietary consumption of allergenic foods.

After 12 months of follow-up, many patients were able to introduce allergenic foods into their diet, with higher success rates for milk, egg, and wheat (61?70 percent) than for peanuts and tree nuts (38?56 percent). According to the investigators, success was defined as a median daily consumption of >300 mg of allergenic food protein by quarterly intervals over 12 months.

The reduction in allergenic food intake seemed to be tied to symptoms and factors such as taste and aversion, with no clear predictors of dietary consumption success. Many patients returned to avoidance due to AEs and other factors. AEs included anaphylaxis, epinephrine use, and two cases of eosinophilic esophagitis potentially related to dietary consumption.

Stage 3 is ongoing, with investigators continuing to evaluate data from patients who completed Stage 2 and entered Stage 3.

Addresses treatment goals of food allergy patients

“Food allergies are becoming more common, leaving millions of families to grapple with constant vigilance, strict dietary restrictions, and disruptions to everyday activities,” said co-lead study investigator Dr R Sharon Chinthrajah from the Sean N Parker Center for Allergy and Asthma Research at Stanford School of Medicine, Palo Alto, California, US, in a news release.

“These findings equip healthcare providers with valuable data on omalizumab and OIT, enabling them to continue to address the diverse needs and treatment goals of their food allergy patients,” said Chinthrajah.

Omalizumab is the first and only US FDA-approved drug for mitigating allergic reactions in children and adults with ≥1 food allergies. Food allergy is the fourth FDA-approved indication for omalizumab.