OUtMATCH: Omalizumab gains FDA nod for IgE-mediated food allergies

Omalizumab scores in the NIH*-sponsored phase III OUtMATCH** trial, increasing the threshold for an allergic reaction to peanut and other common food allergens in children and adults with multiple food allergies.

“[The findings] showed that anti-IgE therapy could significantly reduce the occurrence of allergic reactions across multiple foods in the event of an accidental exposure,” said principal study investigator Dr Robert Wood from Johns Hopkins University School of Medicine, Baltimore, Maryland, US.

After 16 weeks of treatment, nearly 70 percent of paediatric participants who received omalizumab (80 out of 120) were able to consume a single dose of ≥600 mg of peanut protein without dose-limiting symptoms***. With placebo, only 7 percent (four out of 60 patients) were able to achieve the primary endpoint. A comparison between arms yielded an odds ratio of 28 (p<0.0001). [AAAAI 2024, abstract L54]

Key secondary endpoints were also met, with more patients on omalizumab than placebo being able to consume a single dose of ≥1,000 mg of milk (66 percent vs 10 percent), egg (67 percent vs 0 percent), and cashew (41 percent vs 3 percent; p<0.0001 for all) after 16 weeks of treatment.

The approximate equivalent of peanut protein ≥600 mg is 2.5 peanuts or half a teaspoon of regular peanut butter. The ≥1,000-mg dose of milk, egg, and cashew corresponded to 2 tablespoons of 1 percent milk, a quarter of an egg, and 3.5 cashews, respectively. [J Allergy Clin Immunol Pract 2023;11:572-580.e2]

Two of the three adult participants completed stage 1 of the study (one in each arm). The omalizumab recipient achieved the primary endpoint.

The incidence of adverse events (AEs) was similar between the omalizumab and placebo arms. The most common AEs reported with omalizumab were injection site reaction and fever. The safety results generally aligned with the reported safety profile of omalizumab.

“These pivotal results show promise for children, families, and adults living with the constant risk of potentially life-threatening allergic reactions to common food allergens following an accidental exposure,” commented Dr Angelika Jahreis, Development Unit Head, Immunology, Novartis, in a press release. [https://www.novartis.com/us-en/news/media-releases/new-england-journal-medicine-publishes-phase-iii-data-showing-xolair-omalizumab-significantly-reduced-allergic-reactions-across-multiple-foods-people-food-allergies]

In a separate news release, Dr Levi Garraway, Chief Medical Officer, Genentech, noted that “[omalizumab] offers patients and families an important new treatment option that can help redefine the way food allergies are managed and reduce the often-serious allergic reactions that can result from exposure to food allergens.” [https://www.gene.com/media/press-releases/15019/2024-02-16/fda-approves-xolair-as-first-and-only-me]

Treatment options remain scarce

“Food allergies affect millions of individuals in the US, and those impacted face a daily threat of life-threatening reactions. This can lead to substantial anxiety with a profound effect on quality of life,” noted Wood in another report. [https://www.aaaai.org/about/news/news/2024/omalizumab]

“Over the past 35 years, I have seen how debilitating food allergies can be for patients and their loved ones, as they are consumed by fear of accidental exposure,” Wood said. “While allergic reactions to exposures are common and often severe, there have been limited treatment advancements for food allergy.”

The team conducted this three-stage trial to assess the efficacy and safety of omalizumab in individuals aged 1–55 years who were allergic to peanuts and at least two other common foods. In stage 1, 180 patients (177 children and adolescents; three adults) were randomized 2:1 to receive either subcutaneous omalizumab or placebo every 2 or 4 weeks for 16–20 weeks. The dose and dosing interval were determined by total serum IgE level and body weight at baseline.

After the treatment phase, four separate blinded food challenges were completed, wherein participants received gradually increasing amounts of peanut protein, two other food proteins they were allergic to, and a placebo component.

First FDA-approved drug for IgE-mediated food allergies

The findings led to omalizumab’s recent approval by the US FDA for its expanded use in children and adults with IgE-mediated food allergies. It is the first and only FDA-approved drug for reducing allergic reactions in individuals with ≥1 food allergies. [https://www.fda.gov/news-events/press-announcements/fda-approves-first-medication-help-reduce-allergic-reactions-multiple-foods-after-accidental]

“[This] approval builds on 20 years of patient experience and an established efficacy and safety profile since omalizumab was first approved in allergic asthma. We look forward to bringing this treatment to the food allergy community who have long awaited an advancement,” Garraway said.

“We are extraordinarily excited by this advance in the world of food allergy,” said Wood.

Dr Kelly Stone, associate director of the Division of Pulmonology, Allergy, and Critical Care in the FDA’s Center for Drug Evaluation and Research, underscored that “[w]hile it will not eliminate food allergies or allow patients to consume food allergens freely … repeated use [of omalizumab] will help reduce the health impact if accidental exposure occurs.”