Edwin H. Kim, MD, is an associate professor of pediatrics at University of North Carolina’s School of Medicine.

Edwin H. Kim, MD

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 

. “You're seeing a real improvement in quality of life. I've seen really positive results with it.”

 approval of omalizumab in February 2024, allergists have continued to explore treatments for patients with multiple food allergies.

 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.

 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.

Outdated guidance that once advised delaying the introduction of common allergens in young children may have also contributed.

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%.

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.

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.

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 

. “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 (

 = .048) and 38.1% receiving low-dose ADP1010 (

 = .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 (

 = .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.

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

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

“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.”

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

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

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

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

Open-label Extension Study of ADP101. Clinicaltrials.gov. Published 2025. Accessed December 15, 2025. 

https://clinicaltrials.gov/study/NCT05243719

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

Articles

Omalizumab, the first biologic approved for multiple food allergies, has significantly improved patients' quality of life by increasing their allergen thresholds. Despite the rise in food allergy prevalence, recent advances in oral and sublingual immunotherapy offer promising treatment options. The investigational candidate ADP101 showed potential in increasing allergen thresholds, although it did not meet its primary endpoint. The future of food allergy treatment may include sublingual immunotherapy and emerging biologics, with ongoing research aiming to personalize therapy and explore cross-protection among allergens.

Innovative therapies and devices are transforming food allergy management, enhancing safety and quality of life for patients and families.

Sayantani Sindher, MD

Michelle Huffaker, MD

 is a phenomenon that touches the lives of almost everyone in some way, whether one is a patient or has a relationship with a patient.

Allergies to food are a significant concern, given the potential for anaphylaxis among those with Type 1 hypersensitivities. In fact, close to 200,000 individuals require emergency medical care for allergic reactions to food allergens and more than 50% of the 33 million adults in the US with food allergies report experiencing severe reactions.

Parents had become concerned over the years about their children reacting to food allergies, so protocols for avoidance of allergens became the norm by the outset of the 21st century. The 2000 recommendations by the American Academy of Pediatrics (AAP) urged avoidance of major allergens such as peanuts, milk, and eggs.

Allergies to these food products appeared to rise among children in the US between 2000 - 2009.

 It was only recently that the allergy research space made a dramatic shift away from avoidance and toward early exposure and immunotherapy, resulting in the landmark 

US Food and Drug Administration (FDA) approval

 in 2020 of AR101 (Palforzia) as the first food allergy-related immunotherapy.

Since 2020, this dramatic shift in the field of food allergy research has given way to a variety of advancements. 2024 represented another major leap forward, with 2 significant FDA approvals: 

Omalizumab was the first treatment designed to prevent anaphylaxis resulting from exposure to 1 or more food allergens in adults and childrens aged 1 year and older with immunoglobulin E (IgE)-mediated food allergies. Epinephrine nasal spray, also known as ‘neffy,’ is the first alternative option to injectable epinephrine (in such products as the EpiPen).

 editorial team reached out to 3 experts in the field of allergy research to discuss these notable advancements, their significance as ‘firsts’ in the allergy space, and what they mean for patients now that they have been approved.

The team spoke with Edwin H. Kim, MD, associate professor of pediatrics at the University of North Carolina’s School of Medicine. We also spoke with Sayantani Sindher, MD, a clinical associate professor of allergy and immunology at Stanford Medicine. Our third expert was Michelle Huffaker, MD, the director of clinical translational medicine in the Allergy Portfolio at the Immune Tolerance Network.

Each of these speakers are leading experts in the field of allergy and immunology. Below are several notable quotes from 3 interviews on the topic of the aforementioned developments in the allergy space in 2024.

On Evolving Allergy Research and New Developments:

 I would absolutely agree that this has been the biggest year I could think of when it comes to food allergy therapeutics and treatment options. Really thinking back over many years, it's really just been about diagnosing the allergy and giving guidance and avoidance. Several years ago, we had the approval of peanut oral immunotherapy as well as clinical use of food products for this type of thing.

But these were very sort of narrow types of treatments that were only available through specialized clinics. So omalizumab being approved by the FDA is a dramatic change when it comes to food allergy. One of the biggest reasons, in my mind, is because pretty much every allergy office in the United States at this point is likely offering omalizumab for asthma or for hives and urticaria. So now to be able to offer that same medication that they have so much experience with for food allergy, inevitably, is going to increase access.

 It felt like a very momentous year for food allergy, with omalizumab, with neffy, and in fact with another product, Palforzia. The age range went down even lower, as it was previously 4 and up and now it's been shifted to 1 year olds and up. That's extending the age group for when we can offer therapies.

I think having all these treatment options early on changes the mindset when we think of allergy care, instead of what we used to do forever where we diagnose and we say ‘Okay great, now you just avoid it, hope for the best, and we'll see what comes around down the line.’ Whereas now, when I'm diagnosing a 5-month-old or 6-month-old, I can provide them with ‘You know, when you turn 1, you have these options.’ There are these other treatment options in the pipeline and there's just a lot more opportunities for patients to decide what's the right track for them.

The patients are very grateful to have options now. For years, it was avoidance and epinephrine auto injectors. And now they are very grateful that the field is moving forward and that there are more treatment options available, even if they don't just choose to elect those treatment options at this time. There are a variety of reasons that they might choose not to, but just having choices and options has really changed things for those patients.

On Omalizumab and Its Impact on Patients:

I think the earliest patients are on the therapy at this point. So it will take a little bit of time to really get an assessment of how this truly affects those patients. We know what to expect from the clinical trials, but real life is not always the same. I do want to bring up the point that I started with previously, that it increases access and one of the biggest things that it does is (function as) a treatment that can be given for any and all food allergies.

So it really can potentially address food allergies for almost every patient that's out there. The prior treatments, the oral immunotherapy, really could not. It will be really interesting to see the effect that this treatment has on patients, as well as whether there are ‘ideal patients’ for this or patients with certain food allergies do better than those with other food allergies. (There are) lots of these types of questions, so we can fine tune how we use this in the clinic.

I still remember when it got approved. I was away internationally, and I started getting texts from all my colleagues, along with emails. Patients were reaching out when the FDA first approved it, so my colleagues and I have been very excited about this development…One of the reasons I'm super excited is that it gives patients and families choices, because that's one of the things I am hoping for, with more and more advancements coming through…It is great for anyone who doesn't want the hassle of daily oral immunotherapy, which we can address later.

This has been a very exciting year for the world of food allergy and for patients and families dealing with food allergies. And one word you said there really hits on how omalizumab changes the landscape, and that's that's the word ‘options.’ Traditionally, food allergies have been managed completely with avoidance and managing reactions with epinephrine.

It can be frightening for patients. It can be frightening for families. It can be very challenging to avoid all the food allergens and what omalizumab does is it's an extra safety net against those accidental exposures. So decreases the likelihood that anaphylaxis will occur if you were to have an accidental exposure. And so it really opens up options for patients, it potentially liberalizes their diet. It also really changes the level of anxiety that there may be around food allergy.

On the Impact of Epinephrine Nasal Spray:

 I think this has the potential to have a dramatic effect, because every patient out there who has food allergy should have an epinephrine auto-injector to be used as treatment if they were to have an allergic reaction. So a change to that has the potential to affect pretty much every patient that's out there. We know that this is separate from the treatments, because the treatments are there to prevent allergic reactions, but when allergic reactions happen, we know that epinephrine is the best medicine.

That first line medicine that will treat all the symptoms and ideally prevent symptoms from becoming more significant or more severe. At the same time, what we have understood anecdotally, but also now more from actual data on usage, is that a lot of folks that could and should be using that epinephrine auto-injector just haven't been for a multitude of reasons. One of the biggest ones being the injection route itself. So now to have a medication that I hope people are going to be more willing to use, it'll be fantastic to see what kind of effect this will have from the usage of the medication and, hopefully, prevent more significant allergic reactions.

 I think a lot of our adolescent patients are very excited. They love the idea of just being able to spray in their nose and not the injection. We've had so many. We do a lot in our research unit and we do a lot of food challenges. As part of participation in a clinical trial, we have to show that you are truly allergic to a food, and the gold standard of diagnosis is giving them the food that they're allergic to and waiting for a reaction and then treating that reaction.

So we see kids and adults just more terrified about the injection than about the reaction itself. We've had patients who have sat through anaphylaxis on their own because they didn't want to inject themselves. There's also user error. Some parents may have injected themselves instead of the child in the process. So there's lots of kinds of barriers to getting optimal care when it comes to the injectables.

It is another exciting new option for patients in the world of food allergy. It's still kind of coming into the market, so we're still seeing how patients are adopting it. I think one thing that I'm hopeful about with it is that it will lower the bar for use of epinephrine. Giving yourself an injection often feels like a very big deal to patients, even though that really should be the first thing they turn to with systemic allergic reactions. Previously, we only had that through injection.

What I'm hoping is that patients that may be hesitant to give themselves an epinephrine injection would potentially give themselves a nasal spray of epinephrine, if the treatment is just as effective as the injectable form. As a clinician, I don't care which one gets into them, but I want one of them to get into them for patients having a reaction. So if the nasal spray can lower that bar for use, its has potential to save lives.

The quotes contained in this article were edited for the purposes of clarity. For further information, view the interviews posted above.

Kim has reported consulting fees from ALK-Abelló, Ukko Inc., Cellergy Pharma, DBV Technologies, Genentech, Hanimune Therapeutics, Novartis, Nutricia, Phyalxis BioScience, and Revolo Biotherapeutics; safety review committee membership with Allergy Therapeutics Ltd.; royalties from UpToDate; and has stock options for Cellergy Pharma.

Sindher has reported receiving research grant support from NIH, FARE, CoFAR, DBV, AIMMUNE, and Regeneron and has worked as an advisor for Genentech.

Facts and Statistics. Food Allergy Research & Education. https://www.foodallergy.org/resources/facts-and-statistics?gad_source=1&gclid=Cj0KCQiAm4WsBhCiARIsAEJIEzXD8KiNDPvqo8HvRtRBBTjbmyyWhktLJrOiNjLUEqTNRSyo_6_4Z3caAl0JEALw_wcB. Date accessed: December 16, 2024.

Committee on N. Hypoallergenic infant formulas. Pediatrics. (2000) 106(2):346–9. 10.1542/peds.106.2.346. Date accessed: December 16, 2024.

Branum AM, Lukacs SL. Food allergy among children in the United States. Pediatrics. (2009) 124(6):1549–55. 10.1542/peds.2009-1210. Date accessed: December 16, 2024.

FDA approves Xolair® (omalizumab) as first and only medicine for children and adults with one or more food allergies. Novartis. February 16, 2024. https://www.novartis.com/us-en/news/media-releases/fda-approves-xolair-omalizumab-first-and-only-medicine-children-and-adults-one-or-more-food-allergies#:~:text=EAST%20HANOVER%2C%20N.J.%2C%20Feb.,patients%20aged%201%20year%20and. Date accessed: December 16, 2024.

Office of the Commissioner. FDA approves first nasal spray for treatment of anaphylaxis. U.S. Food and Drug Administration. August 9, 2024. Accessed August 9, 2024. https://www.fda.gov/news-events/press-announcements/fda-approves-first-nasal-spray-treatment-anaphylaxis. Date accessed: December 16, 2024.

Videos

Kim, Sindher, Huffaker spoke with HCPLive about some of the year’s most important developments in the food allergy space, namely the approvals of omalizumab and neffy.