First Medicine To Reduce Allergic Food Reactions Approved By The FDA

Mast cells in peripheral blood. Degranulation of mast cells releases histamine that triggers anaphylaxis. By Ayman Qasrawi at English Wikipedia - Transferred from en.wikipedia to Commons., Public Domain, https://commons.wikimedia.org/w/index.php?curid=35421736

How common is food allergy? Each year in the United States, an estimated 6.8 million adults (2%) and roughly 13.6-27.3 million children (4-8%) are affected by food allergies. This widespread issue leads to approximately 30,000 emergency room visits, 2,000 hospitalizations, and tragically, 150 deaths annually.

Peanut allergy is the most common food allergy and is often considered a lifelong condition. However, according to the American College of Allergy, Asthma & Immunology, approximately 20% of individuals with peanut allergy will outgrow it. People with peanut allergies typically experience more severe allergic reactions compared to those allergic to other foods. Allergies to milk, soy, egg, and wheat often resolve during childhood or adolescence.

Despite the vigilance of individuals with peanut allergies regarding peanut allergens in their food, the risk of accidental exposure remains significant. Studies conducted in the United States and Canada have reported that 11% to 17% of accidental exposures resulted in severe reactions. In a cross-sectional study in the United States, 754 children with peanut allergies had an anaphylaxis rate of 14.2%, compared with 8.1% in children with other food allergies. Among adults with peanut allergies, 68% reported experiencing at least one severe peanut allergy, compared to an overall rate of 51% for severe reactions to any food allergen. Currently, there is no cure for food allergies.

Novartis has released data from Stage 1 of 3 of their NIH-sponsored Phase III Omalizumab as Monotherapy and as Adjunct Therapy to Multi-Allergen Oral Immunotherapy in Food Allergic Children and Adults (OUtMATCH) study on XOLAIR™ (omalizumab). XOLAIR™ was granted FDA approval on February 16, 2024, for expanded use in adults and children aged 1 year and older with IgE-mediated food allergies to mitigate allergic reactions resulting from accidental exposure to one or more food allergens. Other indications for XOLAIR™ include asthma, chronic rhinosinusitis with polyps, and chronic spontaneous urticaria.

Clinical Trial Study Design: 

The NIH-sponsored OUtMATCH study on XOLAIR™ (omalizumab) is a Phase III, three-stage, multicenter, randomized, double-blind, placebo-controlled study evaluating Xolair safety and efficacy in patients aged 1 to 55 years who are allergic to peanuts and at least two other common foods.

The main objective of Stage 1 was to determine the efficacy of omalizumab as monotherapy in 180 patients (177 children and adolescents and 3 adults) for 16 to 20 weeks. The main objective of Stage 2 is to compare the efficacy of patients on short course of omalizumab plus multi-allergen oral immunotherapy and long course of omalizumab monotherapy on reducing allergic reactions. Stage 3 involves determining the patients’ ability to withstand normal food that they’re allergic to after cessation of both treatments.

Let us dive into Stage 1 a little bit more in depth. Patients consisted of those who could not tolerate up to 100 mg of peanuts (1/3 of a peanut) and up to at least 2 of 300 mg of walnut, milk, egg, cashew, hazelnut, or wheat. After 16-20 weeks of treatment or placebo, the patients participated in four separate blinded food challenges to assess their ability to tolerate up to 600 mg of peanuts and at least 2 of 1,000 mg dose of walnuts, milk, eggs, cashews, hazelnut, and wheat, without experiencing moderate or severe allergic reactions. The patients were monitored for any moderate to severe allergic reactions.

Results:

Patients receiving omalizumab were able to raise their threshold of peanuts and other foods required to trigger moderate to severe allergic reactions in individuals allergic to multiple foods, including those as young as one year old. The most common adverse event was site injection reaction (9%).

Figure 1. Primary Endpoint. Xolair Treated Patients were able to consume peanuts* (≥ 600 mg) more than placebo treated patients. Total patients: 177. *600 mg of peanuts is equivalent to 2.5 peanuts or ½ tablespoon of peanut butter. 95% CI for difference: 47 to 70; p<0.001

67% of patients on omalizumab were able to tolerate at least 600 mg of peanuts compared to placebo treated patients.

Figure 2. Secondary Endpoints: Xolair Treated Patients were able to consume cashews (≥ 1000 mg); 95% CI for difference: 19 to 52; p<0.001, eggs (≥ 1000 mg); 95% CI for difference: 46 to 79; p<0.001, and milk (≥ 1000 mg); 95% CI for difference: 30 to 74; p<0.001, more than placebo treated patients. *1000 mg of cashew is equivalent of 3.5 cashews; 1000 mg of an egg is equivalent of ¼ of an egg; 1000 mg of milk is equivalent to 2 tablespoons of milk.

Omalizumab treated patients demonstrated tolerance to 41% of cashews, 67% of eggs, and 66% of milk. While a higher percentage of omalizumab treated patients were also able to tolerate walnut, hazelnut, and wheat, statistical significance was not observed.

Impact: 

The expanded utilization of XOLAIR™ for accidental exposure to allergenic foods represents a significant advancement in allergy management, offering numerous advantages to patients. XOLAIR™ works by reducing the likelihood of allergic reactions stemming from accidental exposure, thereby enabling patients to tolerate food ingestion that would have otherwise triggered life-threatening allergic responses. However, it is important for individuals to continue avoiding specific allergenic foods despite XOLAIR™ treatment, as it serves as an additional preventive measure rather than a standalone solution.

Moreover, XOLAIR™ can provide a crucial window of opportunity for managing allergic reactions in cases of epinephrine pen failures or user errors, ensuring prompt medical assistance. Despite epinephrine remaining the primary treatment for anaphylaxis, the occurrence of epinephrine pen failures underscores the importance of alternative interventions. User errors, such as improper self-injection technique (not holding the pen in place for at least 5 seconds or failure to apply pressure to active the pen), have been implicated in adverse outcomes, emphasizing the need for effective preventive measures like XOLAIR™.

Furthermore, food allergies often induce emotional distress and anxiety in both affected individuals and their caregivers. Parents, in particular, experience heightened vigilance and stress regarding their children's dietary choices, often necessitating special dietary accommodations at schools. Additionally, food allergies can significantly impact children's psychological well-being, leading to social avoidance behaviors and dietary restrictions beyond what is medically necessary. XOLAIR™ has the potential to alleviate this burden by reducing the frequency and severity of allergic reactions, thereby mitigating stress and anxiety associated with food allergies.

While the data demonstrates the efficacy of continuous XOLAIR™ use over 16-20 weeks in enhancing tolerance to allergenic foods, several crucial questions remain unanswered. Further research is warranted to elucidate the long-term effects of XOLAIR™ post-treatment cessation, including the duration of its therapeutic effects and optimal dosing regimens. Again, it is essential to emphasize that XOLAIR™ does not represent a cure for food allergies; however, its FDA approval marks a significant milestone in allergy management, offering hope and improved quality of life for affected individuals.

*I am not affiliated with or a representative of the NIH-sponsored study, nor do I conduct or represent clinical trials. This blog is an independent platform dedicated to providing information and insights on various aspects of the pharmaceutical and biotech industry, healthcare, and scientific advancements.*