Date: 2014-04-16
Type of information: Presentation of results at a congress
phase: pediatric study
Announcement: results
Company: DBV Technologies (France) AP-HP (France)
Product: Viaskin® Peanut
Action
mechanism: Summary from CFA 2014 Presentations and Recent Scientific Publications: Epicutaneous immunotherapy (EPIT) allows to safely treat life-threatening allergies, notably in pediatric patients, potentially inducing a powerful, long lasting and protective immune response. During an oral presentation, Dr. Vincent Dioszeghy will explain the mechanisms resulting into specific cellular induction via T-regulatory cells (T-reg). Compared to sublingual immunotherapy (SLIT), EPIT induces a different T-reg phenotype, which in turn could have positive consequences on the induction of long-term protection against sensitization to other allergens. A recent scientific publication in Clinical and Experimental Allergy, “The regulatory T cells induction by Epicutaneous immunotherapy is sustained and mediates long term protection from eosinophilic disorders in peanut sensitized mice”, shows that the protection induced by EPIT is T-reg dependent. EPIT modulates the allergen-specific T cell response via a mechanism that seems to differ from other specific immunotherapy routes, supporting a promising and long-lasting
treatment effect in food allergies.
Disease: peanut allergy
Therapeutic area: Allergic diseases - Immunological diseases
Country: France
Trial
details: ARACHILD is a multicenter double blind, placebo-controlled clinical trial designed to assess the efficacy and safety of epicutaneous immunotherapy (EPIT) using DBV’s Viaskin Peanut in 54 randomized subjects aged 5 to 17 with a confirmed severe peanut allergy. Subjects who reacted to a cumulative dose of peanut proteins of less than 300mg were eligible and randomized to either Viaskin Peanut at 100µg of peanut proteins (active group) or to Viaskin Placebo (placebo group) in a 1:1 ratio. At 6 months, all patients were switched to active treatment and received Viaskin Peanut for an additional 12 months. (NCT01197053)
Latest
news: * On April 16, 2014, DBV Technologies has announced that 4 communications were presented at the French Congress of Allergy (CFA). This year, highlights included an abstract authored by Dr. Bourrier from Pediatric Hospital in Nice (CHULENVAL) and Pr. Dupont from Assistance Publique Hôpitaux de Paris (AP-HP) at the CFA in Paris, April 15-18, 2014 reporting for the first time that a case subject from the ARACHILD Phase II study after an 18-month EPIT treatment maintained its desensitization level after one year off-treatment, with a strict peanut diet. * On June 19, 2013, DBV Technologies has announced the 6-, 12- and 18-month efficacy data of Arachild, a study sponsored by Assistance Publique-Hôpitaux de Paris (AP-HP). The analysis of the data shows that two-thirds of children less than 12 years old reach the efficacy endpoints after 18-month treatment with Viaskin Peanut 100 µg. The serological response observed over the period was robust and strong, implying efficacy of the ongoing desensitization process. In the active group (28 subjects), the 12- and 18-month data shows consistent and sustained improvement across the study population, with 20% and 40% of subjects respectively consuming at least 10 times more peanut protein than at the beginning of the trial (defined as ‘success’ or ‘responders’). The preliminary 6-month data released in June 2012 was partially validated after database cleaning; serological results were fully confirmed while no statistical difference appeared anymore in the treated versus placebo groups at food challenge. After 6-month treatment, the analysis (pooled on 50 subjects) shows that 5 children multiplied by at least 10-fold the cumulated reactive dose of peanut proteins compared to baseline versus 2 children in the placebo group (26 subjects). A specific sub-analysis of results in 19 adolescents (12-17 years old) and 35 children (5 to 11 years old) shows clear-cut trends. Despite a positive serological response, adolescents showed no responders at 6-, 12- and 18-month, while children showed constant and progressive increase in number of responders, with respectively 14.7%, 28.1% and 66.7% of responders at 6-, 12- and 18-month. Overall, children were able to eat on average, after 18 months of Viaskin Peanut treatment, a cumulated reactive dose of approximately 1.5 peanut, compared with traces at the start of the trial. Among the 10 children who passed the food challenge, 4 reached the cumulative reactive dose of more than 1000mg of peanut protein (equivalent to 4 peanuts). Viaskin® Peanut also showed significant immunological changes (secondary efficacy endpoints) in the overall population, with clear-cut results in children. In treated children, peanut-specific IgE (immunoglobulin E) were increased by more than two-fold at 6-month, before decreasing and approaching toward initial levels at 18-month, while Peanut-specific IgG4 (immunoglobulin G4) increased by more than eight-fold over 18-month of treatment. The trends observed in both indicators suggest – as expected – a successful desensitization process in children while the response observed in adolescents was clear, but not robust enough to generate significant clinical outcomes for that specific patient population. Pr. Jean-Marc Tréluyer of the Unité de Recherche Clinique at Tarnier Hospital (AP-HP, Paris, France) led ARACHILD. Pr Christophe Dupont, coordinator of the study, provided DBV with cleaned and comprehensive top-line efficacy data, which were presented to DBV’s Scientific Advisory Board on June 14, 2013. The complete efficacy and safety study results should be published in the coming months by Pr. C. Dupont.
Summary of Poster from Dr. Bourrier and Pr. Dupont: The Abstract highlights an 8-year-old patient from the ARACHILD trial, who voluntarily stopped the EPIT treatment after reaching 1,146mg peanut protein (4 to 5 peanuts) during the 18-month food challenge, from 96,33 mg peanut protein at entry (1/3 peanut). After 12 months of no treatment and following a strict non-peanut diet, the child performed another food challenge and was able to reach again a cumulative reactive dose of 1,110 mg peanut protein. Both investigators concluded that this case is the first documented case in humans of a persistent efficacy induced by EPIT despite a continued and prolonged absence of exposure with the allergen after immunotherapy.
