Epicutaneous immunotherapy for the treatment of peanut allergy

Abstract

Peanut allergy treatment options remain limited, but novel approaches are being studied, including epicutaneous immunotherapy (EPIT). EPIT uses the cutaneous immune system to promote tolerance to food allergens. Viaskin™ Peanut, an approach to EPIT in late-stage clinical development uses an occlusive patch with a condensation chamber that enables natural epidermal water loss to solubilize dry antigen on the patch, which is then absorbed and captured by skin Langerhans cells. This form of EPIT does not require disruption of the skin barrier, thus avoiding a proinflammatory cytokine response by targeting the nonvascularized epidermis and limiting systemic allergen exposure. Extensive preclinical research suggests that Viaskin Peanut has a distinct mechanism of desensitization, including the potential for disease modification, driven by a unique population of regulatory T cells. Numerous clinical studies of Viaskin Peanut have demonstrated desensitization and reductions in reaction severity, particularly in children aged 1 through 11 years, as well as a favorable safety profile with mostly mild-to-moderate skin reactions that were observed to decrease over time. EPIT with Viaskin Peanut may be a potential therapeutic option for peanut allergy that is clinically practical with long-term efficacy and tolerability.

Keywords: Viaskin Peanut; epicutaneous immunotherapy; food allergy; peanut allergy.

FIGURE 1

Layers of the Skin. Reprinted from Bird et al. CD, cluster of differentiation; DC, dendritic cell; ILC, innate lymphoid cell. The skin is composed of specialized cells that assist in carrying out various functions to defend against pathogens.

FIGURE 2

Condensation Chamber of Viaskin. (A) The occlusive patch contains dried native allergen extracts, which are electrosprayed onto a backing film disc that is held above the skin. (B) The condensation chamber enables water loss to solubilize the dry antigen, and the allergen is presented to the superficial layers of the epidermis.

FIGURE 3

Proposed Mechanism of Action of EPIT. Reprinted with permission from Hervé et al. APCs, antigen‐presenting cells; LC, Langerhans cells; Tregs, regulatory T cells. LCs process the antigen, travel to the lymph nodes, and lead to a Treg‐mediated immune response.

FIGURE 4

Reduction in Reaction Severity During DBPCFC., DBPCFC, double‐blind, placebo‐controlled food challenge. In both EPITOPE and PEPITES, the maximum severity of reactions (none, mild, moderate, or severe) during baseline DBPCFC was similar between treatment groups; however, at Month 12 DBPCFC, there was a statistically significant difference in the distribution of symptom severity.

FIGURE 5

Local Skin Reactions in the Peanut‐Patch Group Over Time per Investigator's Assessment (PEPITES). Adapted from Fleischer et al. Reaction definitions: Grade 1, only erythema, or erythema + infiltration; Grade 2, erythema, few papules; Grade 3, erythema, many or spreading papules; Grade 4, erythema, vesicles. Local skin reactions in VP250‐treated participants decreased in frequency and severity after the first month of treatment.

FIGURE 6

Clinical development stages of Viaskin Peanut. EPIT with Viaskin Peanut has been studied across multiple phase 2 and 3 trials, which included ~1300 participants exposed to active treatment.

FIGURE 7

Goal of immunotherapy. The likelihood of having a reaction to the allergen decreases as the eliciting dose increases.

FIGURE 8

Hallmarks of a clinically useful intervention. TEAEs, treatment‐emergent adverse events. Epicutaneous immunotherapy with Viaskin Peanut may be a potential option to desensitize peanut‐allergic children aged 1 through 11 years. Viaskin Peanut has demonstrated desensitization and reductions in reaction severity in clinical trials with a favorable safety profile, while also being practical to use with no limitations to daily activities or restrictions with exercise.