Omalizumab increases reaction threshold for multiple common food allergies

Phase 3 data for recently FDA-approved omalizumab (Xolair; Novartis and Genentech) has been published in The New England Journal of Medicine (NEJM), highlighting an increased reaction threshold for peanut and other common food allergens in people as young as 1 year of age.^1,2

The data, from stage 1 of the phase 3 OUtMATCH study (NCT03881696) were featured in a late-breaking symposium at the 2024 American Academy of Allergy, Asthma & Immunology (AAAAI) Annual Meeting.¹

According to The NEJM, investigators assessed if omalizumab would be safe and effective as a monotherapy in patients with multiple food allergies.²

Individuals aged 1 year to 55 years were screened to receive either the monoclonal anti-IgE antibody or placebo, administered subcutaneously every 2 to 4 weeks for 16 to 20 weeks.²

In all, 462 individuals were screened, while 180 underwent randomization. Ingestion of peanut protein in a single dose of 600 mg or more without dose-limiting symptoms was the primary outcome.²

Secondary outcomes included consumption of cashew, milk, and of egg in single doses of at least 1000 mg each, without dose-limiting symptoms, wrote the study investigators.²

The of the 180 participants, 177 were children and adolescents aged 1 to 17 years. There were 118 participants assigned to receive omalizumab, of which 79 (67%) met the primary endpoint compared to 4 of 59 (7%) participants who received placebo (P < 0.001).²

"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 the fear of accidental exposure,” said Robert Wood, MD, director of the Eudowood Division of Allergy, Immunology and Rheumatology at Johns Hopkins Children's Center, and principal investigator of the OUtMATCH study, in a press release from Genentech.¹

"While allergic reactions to exposures are common and often severe, there have been limited treatment advancements for food allergy," added Wood. "The results of the OUtMATCH study showed that anti-IgE therapy could significantly reduce the occurrence of allergic reactions across multiple foods in the event of an accidental exposure."

Secondary endpoints were consistent with the primary endpoint²:

• Cashew - 41% vs 3% (P < 0.001)
• Milk - 66% vs 10% (P < 0.001)
• Egg - 68% vs 0% (P < 0.001)

According to The NEJM, safety endpoints "did not differ between the groups, aside from more injection-site reactions in the omalizumab group."²

“Living with food allergies has a profound impact on patients and their families, causing significant stress and requiring constant vigilance,” said R. Sharon Chinthrajah, MD, associate professor of medicine, Stanford School of Medicine, Sean N. Parker Center for Allergy and Asthma Research, OUtMATCH co-lead study investigator in the release.¹

“The OUtMATCH study demonstrated that anti-IgE therapy increased most patients’ threshold for an allergic reaction. This presents an important new treatment option for patients and families in its potential to reduce the risk of allergic reactions from accidental exposures they may face in day-to-day life," added Chinthrajah.¹

The first 60 individuals who completed the first stage of the phase 3 study were enrolled in a 24-week open-label extension. For 38 children in this group, "the percentage of patients who were able to consume 600 mg or more of peanut protein and 1,000 mg or more of egg, milk and/or cashew protein without moderate to severe dose-limiting symptoms was maintained," stated Genentech.^1,2

Omalizumab treatment for 16 weeks was, "superior to placebo in increasing the reaction threshold for peanut and other common food allergens," in people as young as 1 year of age with multiple food allergies, the study investigators concluded.²

The company noted that people taking omalizumab for food allergies should keep avoiding all foods they are allergic to, and that omalizumab should not be used for the emergency treatment of any allergic reaction.¹

Scott Sicherer, MD, FAAP, director, Jaffe Food Allergy Institute, Ichan School of Medicine, Mount Sinai, New York, New York, and an author of The NEJM paper, provides commentary below regarding these data and the FDA approval of omalizumab.

Scott Sicherer, MD, FAAP:

The results of the study and the FDA approval are very exciting and provide a needed option for so many people with severe and multiple food allergies. The drug was able to provide an increase in reaction threshold to multiple foods for most of the people treated. Many had substantial increases. This means that for most people treated, there is safety at least for small accidental ingestions that could have otherwise caused reactions.

This is “huge” because there are many people who have reacted to small exposures and this causes anxiety, poses risks at every meal, snack and social activity with food, and ends up limiting quality of life. Families and people with food allergies are often looking to be “bite safe” from accidents and most people have multiple food allergies. So, this approval of an effective treatment is truly life-changing.

Having said that, it is important to understand it did not work for everyone, and the effect varied. Right now, we do not have an easy way to know how much protection an individual has and the instructions are to maintain the food avoidance and be prepared to treat any reactions as before. In the study, medically supervised feeding tests (oral food challenges) were used to determine the change in threshold of reaction. Potential patients must also understand that this is not a cure and the effect of the drug wears off if it is stopped.

Assuming a patient has qualifying laboratory tests and allergies to be a potential candidate for treatment, allergists will be having detailed discussions with their patients and families for shared decision-making to determine those who are a good fit for this treatment.

They will be discussing the severity of their past reactions, success of avoidance, impact on daily life, the foods they are avoiding, and many other factors. Whether the patient has asthma or respiratory allergy that [could also] benefit from this treatment may be part of the assessment.

There will also be a lot of counseling about what is or is not different for them being on this treatment. For example, still carrying epinephrine and avoiding the food, still informing the restaurant of the allergies but knowing that the restaurant meal is likely less risky should there be an error. Or, telling the school to have very careful supervision of the child with food allergies, but knowing if the young child accidentally grabbed food from another child and took a bite, the risk is reduced, [but not eliminated]. The treatment may be more or less meaningful depending upon many factors.

It is interesting that many had very substantial increases in their threshold. More studies are needed to understand about options beyond continued avoidance while being treated with omalizumab (and the OUtMATCH study has stages 2 and 3 looking at these questions. The studies are still underway).

References:

1. New England Journal of Medicine publishes phase III data showing Xolair significantly reduced allergic reactions across multiple foods in people with food allergies. Genentech. Press release. February 25, 2024. Accessed February 26, 2024. https://www.gene.com/media/press-releases/15020/2024-02-25/new-england-journal-of-medicine-publishe

2. Wood RA, Togias A, Sicherer SH, et al. Omalizumab for the treatment of multiple food allergies. N Engl J Med. Published online February 25, 2024:NEJMoa2312382. doi:10.1056/NEJMoa2312382