A New Era in Food Allergy Treatment: The Push Toward Multi-Allergen Immunotherapy

Imagine avoiding your favorite coffee shop because the milk steaming in the air could trigger a severe allergic reaction. That was the reality for a patient of Ruchi Gupta, MD, until they began treatment with omalizumab (Xolair), the first biologic approved to target multiple food allergies. Today, the patient can enter the café freely with no reactions, no fear.

Omalizumab proved life-changing for the patient by targeting multiple food allergies in a single therapy.

“It’s not a cure, but it's increasing their thresholds to a point where they are not as worried, especially our most severely allergic patients and multi-allergic patients,” Gupta, a professor of pediatrics at Feinberg School of Medicine, Northwestern University, told HCPLive. “You're seeing a real improvement in quality of life. I've seen really positive results with it.”

Following the US Food and Drug Administration (FDA) approval of omalizumab in February 2024, allergists have continued to explore treatments for patients with multiple food allergies.1 The year 2025 marked a turning point in this space, bringing new research on oral immunotherapy (OIT), a head-to-head trial comparing omalizumab with OIT, and growing anticipation around upcoming studies of sublingual immunotherapy.

Food allergy prevalence has risen by 50% since the 1990s, according to the Centers for Disease Control and Prevention (CDC), with roughly 33 million people in the United States now living with food allergies.2 Experts point to several contributing factors, including the hygiene hypothesis, heightened awareness, shifts in the microbial environment, vitamin D levels, and rising caseation delivery rates.2

Outdated guidance that once advised delaying the introduction of common allergens in young children may have also contributed.3 The landmark LEAP trial, published in 2015, challenged this approach, demonstrating that early peanut introduction significantly reduced allergy risk. Supporting this shift, recent data suggest that 10 years after the American Academy of Pediatrics recommended early peanut introduction, peanut allergy rates declined by 27%.4

Despite these advances, many infants continue to avoid common food allergens, coinciding with persistently high allergy prevalence. A 2024 FARE report found that approximately 40% of children with food allergies react to more than 1 food.1

Food allergies can profoundly affect daily life, as fear of reactions, visible swelling, and dismissive attitudes from others can limit social interactions. These factors highlight the importance of therapies that address multiple food allergies, an area in which 2025 research has offered meaningful steps forward.

The Push Toward Multi-Allergen OIT

Multi-allergen oral immunotherapy has gained renewed attention with the investigational candidate ADP101.

“It's very exciting because we see almost over 50% really developing tolerance [with multi-food allergen OIT], so not just increasing your threshold, but potentially reversing it and allowing you to eat freely,” Gupta said. “[With] the biologic, we're still waiting to see if this could actually reverse it and allow you to eat freely or just to increase your threshold.”

ADP101, a novel, pharmaceutical-grade OIT, showed promise in the phase ½ Harmony trial for increasing the reactive threshold in children aged 4 - 17 years with single or multiple food allergies. This formulation contained equal amounts of allergenic proteins from 15 foods: almond, cashew, chicken’s egg, codfish, cow’s milk, hazelnut, peanut, pecan, pistachio, salmon, sesame, shrimp, soy, walnut, and wheat.

However, this study did not meet its primary endpoint, defined as the proportion of participants tolerating a ≥600 mg challenge dose without dose-limiting symptoms at week 40 during a double-blind, placebo-controlled food challenge (DBPCFC).

“I do think that it was just a very difficult study to do in the first place,” said Edwin Kim, MD, an investigator on the Harmony trial and a professor of allergy at the University of North Carolina at Chapel Hill, in an interview with HCPLive. “As soon as you bring in multiple allergens, multiple variables, it gets harder and harder to meet the statistical significance that we're looking for. I do think…if we continue to treat for longer or [conduct a] larger study, we would see better results.”

Although this study missed its primary endpoint, the data showed that more than half of the participants (55%) receiving high-dose ADP101 (P = .048) and 38.1% receiving low-dose ADP1010 (P = .306) tolerated a ≥ 600 mg challenge dose, compared with 20% in the placebo group. After completing the exit DBPCFC, 68.8% on high-dose ADP101 (P = .015) and 53.3% on low-dose ADP101 (P = .144) responded to treatment, compared to 23.5% on placebo.

For Kim, the most meaningful finding was the increase in allergen thresholds across multiple foods, reinforcing the broader applicability of OIT beyond peanut.

“It makes sense that the thresholds that we achieve for different foods may be slightly different, but I wouldn't expect them to be dramatically different,” Kim said. “To be able to see increased thresholds across several different unrelated foods was probably the most reassuring part of the study to me.”

ADP101 demonstrated a favorable safety profile, with most adverse events mild or moderate. Among the 61 participants, 75% on high-dose ADP101 and 76.2% on low-dose ADP101 experienced ≥ 1 treatment-emergent adverse event, compared with 60% of those receiving placebo.

According to ClinicalTrials.gov, the open-label extension of ADP101 was terminated due to a sponsor decision.5

Even so, the pursuit of oral immunotherapy for multiple food allergies is far from over, and in many respects, it is not new.

Multi-Allergen OIT in Clinical Practice

Hugh Windom, MD, an allergist from Southgate, Florida, said he has treated patients with multiple food allergies in his clinical practice for years, long before the concept gained traction in clinical trials.

“I don't separate [multiple food allergy [from] single food allergy,” Windom told HCPLive.

“If the concept of oral immunotherapy works, which it does with 1 food, it's going to work with multiple foods. So, it really was never a gigantic leap to go from 1 to 2 to 3. Historically, we've been [giving] allergy shots for over 100 years, and we don't give [just cat or ragweed] allergy shots. We give multi-allergen shots every day of the week.”

He said that many clinics begin their patients with a single immunotherapy and later expand to additional allergens, referring to it as a natural progression. He also characterized the current landscape as the “wild west,” largely because of limited standardization beyond protein measurement.

“For many years, we were on the outside because there's no drug company behind us,” Windom said. “We won’t have the funds to adverse and to get FDA approval. We…needbuy-in from our national organizations to say, ‘Hey, this is standard of care.’”

He emphasized the importance of national organizations’ support. Allergies can be eliminated in children less than 5 years old, but children older than 5 will continue to have allergies and can only have symptoms lessened.

Future of Multiple Food Allergy Treatment: Sublingual Immunology

Windom also sees promise in sublingual immunotherapy for both single and multiple food allergies. In Europe, sublingual immunotherapy is commonly used for airborne allergens, such as ragweed and dust mite, often preferred over injections. In the United States, allergists have begun applying sublingual approaches for food allergies. The manufacturer of environmental sublingual tablets is also developing food-based products, including peanut formulations.

That said, many clinicians are not waiting for commercial products to reach the market. Instead, Windom said allergists often use real foods, much as they do with oral immunotherapy, placing substances such as peanut flour or milk under the tongue.

“It's a much safer, simpler, less expensive process,” he said. “It’s 4 visits, and you're on [a] top dose…you're gradually becoming desensitized.”

Significant questions persist, particularly regarding the expansion of sublingual immunotherapy beyond the more commonly studied foods, such as milk, egg, peanut, sesame, and certain tree nuts. Data are limited for grains and shellfish, as is the evidence around cross-protection.

“If I treat you with wheat, are you protected against rye or barley or some other grain?” Windom asked. “Could we treat you to shrimp, and would that protect you against other shellfish, lobster, crab? We need to learn more about cross-protection, so we don't need to treat you with 25 foods.”

It is already known that treating cashew covers pistachio and walnut covers pecan, but cross-protection between grains or shellfish remains less well studied.

Additional unanswered questions about multi-allergen immunology, including optimal treatment duration, how best to personalize therapy using genetics, the microbiome, or biomarkers, and whether emerging biologics, such as Bruton tyrosine kinase inhibitors, could expand multi-food protection. It is also unclear whether standardized multi-allergen OIT products will return or whether care will continue in a hybrid model combining clinic-based immunotherapy and biologics.

Looking Ahead in Multi-Allergen Immunology

Gupta noted that a sublingual epinephrine option may arrive as early as 2026. The FDA assigned Anaphylm, a sublingual film formulation of epinephrine, a Prescription Drug User Fee Act (PDUFA) date of January 31, 2026.

“With these new devices for treating allergy reactions, and then all the actual treatments to increase thresholds, I've seen a tremendous change, even in this year, but anticipate even more coming up because people will be able to access them and improve their quality of life,” Gupta said. “Plus, with prevention, with all the babies now eating allergens, maybe we'll be able to prevent this from the beginning and change the tide and actually decrease the incidence of food allergy from the very beginning.”

Gupta described a comic hanging up in her office. In 1 frame, an adult tells a child, “When I was your age, there were no food allergies.” In the other, the adult tells the child, “When I was your age, there were food allergies.”

“I don't know if we can change it in just a generation,” Gupta said. “The goal and the hope is, with all the amazing research happening around the world, that we'll see a big change happen in the next decade.”

References:

1. Smith T. FDA Approves Omalizumab as First Treatment of 1 or More Food Allergies for Children, Adults. Hcplive. Published February 16, 2024. Accessed December 15, 2025. https://www.hcplive.com/view/fda-approves-omalozumab-first-treatment-of-1-or-more-food-allergies-for-children-adults

2. Food Allergy Facts and Statistics for the U.S. Food Allergy Research & Education. Food Allergy Research & Education. Published April 18, 2024. Accessed December 15, 2025 https://www.foodallergy.org/sites/default/files/2024-07/FARE%20Food%20Allergy%20Facts%20and%20Statistics_April2024.pdf

3. Derman C. Microbes, Medicine, Modern Life May Drive Food Allergy Rise, Experts Say. HCPLive. Published May 29, 2025. Accessed December 15, 2025. https://www.hcplive.com/view/microbes-medicine-modern-life-may-drive-food-allergy-rise-experts-say

4. Gabryszewski S, Gupta R, and Hernandez-Trujillo V. Peanut Allergy Rates Plummet 10 Years After AAP Early Introduction Guidelines. HCPLive. Published Octber 30, 2025. Accessed December 15, 2025. https://www.hcplive.com/view/peanut-allergy-rates-plummet-10-years-aap-early-introduction-guidelines

5. Open-label Extension Study of ADP101. Clinicaltrials.gov. Published 2025. Accessed December 15, 2025. https://clinicaltrials.gov/study/NCT05243719

6. Brooks A. FDA Accepts Epinephrine (Anaphylm) Sublingual Film NDA for Type 1 Allergic Reactions. Hcplive.com. Published June 19, 2025. Accessed December 22, 2025. https://www.hcplive.com/view/fda-accepts-epinephrine-anaphylm-sublingual-film-nda-type-1-allergic-reactions