ADP101 Immunotherapy Increases Food Allergy Threshold but Misses Primary Endpoint

Edwin H. Kim, MD

Credit: University of North Carolina School of Medicine

In a recent study, the investigational oral immunotherapy ADP101 increased the reactive threshold in pediatric patients with single or multiple food allergies.¹ However, it did not meet its primary endpoint: the proportion of participants tolerating a ≥ 600 mg challenge dose without dose-limiting symptoms at week 40.

Approximately 20 million people in the US have food allergies, managed through dietary avoidance, education, anti-IgE monoclonal antibody omalizumab, and oral immunotherapy.² Although 30% to 60% of food-allergic US patients have multiple food allergies, the only approved oral immunotherapy targets peanut allergy. Food allergies can be life-threatening, and multiple allergies add a burden, raising the likelihood of accidental exposure, challenges of allergen avoidance, and the risk of nutritional deficiency.¹

“ADP101, with a precise mixture of pharmaceutical-grade allergenic proteins from 15 food sources, has the potential to offer a standardized OIT option for those with a range of prevalent single food allergies, or with multifood allergy,” wrote investigators, led by Edwin H. Kim, MD, from the department of pediatrics at University of North Carolina School of Medicine.

The phase ½ Harmony trial evaluated the efficacy and safety of ADP101, a novel, pharmaceutical-grade oral immunotherapy for multiple food allergies, containing an equal number of allergenic proteins from 15 foods. The study included 61 participants aged 4 – 17 years with 1 – 5 qualifying food allergies, defined as dose-limiting symptoms with a ≤ 100 mg challenge dose of almond, cashew, chicken’s egg, codfish, cow’s milk, hazelnut, peanut, pecan, pistachio, salmon, sesame, shrimp, soy, walnut, or wheat during the double-blind, placebo-controlled food challenge (DBPCFC).

The primary endpoint was the proportion tolerating a ≥ 600 mg challenge dose without dose-limiting symptoms at week 40 of the DBPCFC. Secondary endpoints included the proportion tolerating ≥ 1000 mg of single qualifying food and participants with >1 qualifying food allergy tolerating ≥600 mg or ≥1000 mg of ≥2 qualifying foods at Exit DBPCFC.

Participants were randomized to receive low-dose (1500 mg/d; 100 mg protein per food) or high-dose (4500 mg/d; 300 mg protein per food) ADP101, or placebo. If they tolerated a single 5 mg dose, they continued daily medication for 2 weeks; the dose was increased every 2 weeks until week 38, then maintained through week 40. Participants discontinued treatment if they could not tolerate ≥ 50 mg.

Compared with placebo (20%), 55% of high-dose ADP101 participants tolerated a ≥600 mg challenge dose (P = .048), and 38.1% on low-dose ADP101 (P = .306) showed improvement. However, the trial did not meet its primary endpoint after multiple comparison adjustments (high dose, P = .097; low dose, P = .306). Among pediatric participants completing the Exit DBPCFC, 68.8% on high-dose ADP101 (P = .015) and 53.3% on low-dose ADP101 (P = .144) responded to treatment, versus 23.5% on placebo.

For secondary endpoints, 50% on high dose ADP101, 23.8% on low dose ADP101, and 15% on placebo tolerated a ≥ 1000 mg challenge dose. Among those allergic to ≥ 2 foods, 55.6% on the high dose and 22.2% on the low dose tolerated a ≥ 600 mg challenge dose; 44.4% on a high dose and 11.1% on low dose tolerated a ≥ 1000 mg of ≥ 2 qualifying foods.

Participants on ADP101 had reduced skin-prick test reactivity and increased maximum tolerated dose across most foods. Among those tolerating a ≥1500 mg maintenance dose, response rates increased to 58.1% (600 mg threshold) and 48.5% (1000 mg threshold). Of high-dose participants reaching the 4500 mg maintenance dose, 76.9% had a 600 mg desensitization threshold, and 69.2% reached 1000 mg, with similar results for those with multiple allergies.

Despite missing the primary endpoint, ADP101 demonstrated a favorable safety profile with most adverse events mild or moderate. Overall, 60% on placebo, 76.2% on low-dose ADP101, and 75% on high-dose ADP101 experienced ≥ 1 treatment-related adverse event.

“ADP101, an OIT candidate covering the 15 most prevalent food allergens, was well tolerated and increased the reactive threshold in pediatric participants with single or multiple food allergies, warranting its further investigation,” investigators concluded.

References

1. ^{Kim EH, Carr WW, Assa'ad AH, Gogate SU, Petroni DH, Casale TB, Wang ML, Sullivan A, Archer AM, Wang O, Piscia-Nichols C, Tuomi L, Levin-Young O, Dombkowski A, McClintock D; Harmony investigators. ADP101 multifood oral immunotherapy for food-allergic patients: Harmony phase 1/2 randomized clinical trial. J Allergy Clin Immunol Glob. 2024 Dec 10;4(1):100382. doi: 10.1016/j.jacig.2024.100382. PMID: 39896962; PMCID: PMC11786640.}
2. ^{Allergy Facts. Asthma and Allergy Foundation of America. https://aafa.org/allergies/allergy-facts/#:~:text=As%20of%202021%2C%20about%2020,food%20allergies%20in%20the%20U.S.&text=About%2016%20million%20(6.2%25)%20U.S.%20adults%20have%20food%20allergies.&text=About%204%20million%20(5.8%25)%20U.S.%20children%20have%20food%20allergies. Accessed February 6, 2025.}