Epicutaneous Immunotherapy Shows Favorable Long-Term Safety for Peanut Allergy

The phase 3 REALISE study showed epicutaneous immunotherapy (EPIT) with VIASKIN peanut patch (VP250) had a favorable safety profile, with severe treatment-emergent adverse events decreasing from 9.7% in year 1 to 0.3% in year 3.1

“The safety profile in this long-term study was consistent with the safety results in previous phase 2b (VIPES and OLFUS-VIPES) and phase 3 trials (REALISE DBPC period, PEPITES, EPITOPE) with low rates of treatment-related anaphylaxis, epinephrine use, and discontinuations,” wrote investigators, led by Jacqueline A. Pongracic, MD, from Ann and Robert H. Lurie Children’s Hospital of Chicago at Northwestern University Feinberg School of Medicine.

Individuals with peanut allergies do not have many options when it comes to low-risk treatment. Many people with peanut allergies try to avoid the allergen. Still, since peanuts are a common food ingredient and cross-contamination in factories is possible, accidental exposure can be easy, putting patients at risk of anaphylaxis.

Patients with peanut allergies may consider therapeutic treatment options, but these come with significant risks. For instance, while oral immunotherapy is effective in managing peanut allergies, it is linked to adverse events of nausea, vomiting, eosinophilic esophagitis, and anaphylaxis. Another treatment option is an omalizumab injection for immunoglobulin E-mediated food allergy, but evidence has yet to show this provides a sustained duration of effect.

EPIT with VP250, a novel treatment approach, has been evaluated for safety and efficacy in phase 2 and 3 trials. The phase 3 PEPITES trial showed EPIT with VP250 for 12 months was statistically superior to placebo in desensitizing peanut-allergic children, with treatment responder rates of 35.3% vs 13.6% (P < .001).2 In this trial, VP250 was well-tolerated, with mild to moderate adverse events.

Pongracic and colleagues conducted an open-label extension of the REAL Life Use and Safety of EPIT (REALISE) trial to assess the long-term safety of EPIT with VP250 (250 µg) in a clinical setting that imitated real-world use.1 The sample included 393 children aged 4 – 11 years (54.8% male; median age, 7.2 years) who had a well-documented medical history of a peanut ingestion reaction, peanut-specific immunoglobulin E ≥ 14 kUA/L and skin prick test ≥ 8 mm. The study did not require participants to have any double-blind, placebo-controlled food challenge; thus, children with a history of severe anaphylaxis to peanuts could join.

REALISE began with a randomized, double-blind period where children were randomized 3:1 to receive VP250 or placebo. After 6 months, children entered the open-label extension with 36 months of active treatment.

Most participants (98.7%) experienced ≥ 1 treatment-emergent adverse event. For the most part, treatment-emergent events were mild or moderate, and the severity decreased over time.

The trial found local skin reactions were the most common treatment-emergent adverse event. However, these reactions decreased in frequency from year 1 to year 3. For instance, reactions reduced from 87.8% to 19.2% participants for any site, 68.9% to 13.1% for local erythema, 59.9% to 5.2% for local pruritus, 35.2% to 3.2% for local swelling, and 13% to 1.7% for eczema.

In general, severe treatment-emergent adverse events reduced from 9.7% in year 1 to 0.3% in year 3. Most participants (96.5%) had high adherence to the treatment throughout the 3 years.

“Despite the potential for treatment fatigue, adherence remained high through the last 6 months of treatment, which may be attributed to the simple to use treatment without the need for dose titrations, interruptions due to routine illness, or restrictions with daily activities or exercise,” investigators wrote.

The study identified a low rate of treatment-emergent anaphylaxis (4.1%). For those who did experience anaphylaxis, it was reported during the first year of treatment. Patients who had a history of severe peanut anaphylaxis (n = 14) did not have specific safety signals when on VP250.

“As there are new and emerging treatment options for peanut allergy, it is important to weigh risk versus benefit and the impact on daily activities when discussing potential treatment options,” investigators wrote. “Caregivers report that current treatment options are unsatisfactory, as they desire convenience in addition to treatment efficacy… it is essential to have multiple treatment options from which patients and healthcare providers can choose.”

References

1. Pongracic JA, Gagnon R, Sussman G, Siri D, Oriel RC, Brown-Whitehorn TF, Anvari S, Berger WE, Bird JA, Chan ES, Chinthrajah RS, Chong HJ, Fineman SM, Fleischer DM, Gonzalez-Reyes E, Kim EH, Lanser BJ, MacGinnitie A, Mehta H, Petroni D, Rupp N, Schneider LC, Scurlock AM, Sher LD, Shreffler WG, Sindher SB, Wood R, Yang WH, Sampson HA, Bois T, Green TD, Campbell DE, Bee KJ, Bégin P. Long-Term Safety of Epicutaneous Immunotherapy in Peanut-Allergic Children: An Open-Label Active Treatment (REALISE Study). J Allergy Clin Immunol Pract. 2025 Feb 27:S2213-2198(25)00196-5. doi: 10.1016/j.jaip.2025.02.024. Epub ahead of print. PMID: 40023371.

2. Fleischer DM, Greenhawt M, Sussman G, Bégin P, Nowak-Wegrzyn A, Petroni D, et al. Effect of 689 Epicutaneous Immunotherapy vs Placebo on Reaction to Peanut Protein Ingestion Among Children With 690 Peanut Allergy: The PEPITES Randomized Clinical Trial. JAMA. 2019;321(10):946-955. doi:10.1001/jama.2019.1113