Epicutaneous Immunotherapy (EPIT)
Epicutaneous (“on the skin”) immunotherapy, or EPIT, exposes tolerance-promoting immune cells in the skin to an adhesive dermal patch containing a small (micrograms) dose of food protein. DBV Technologies has developed the Viaskin® dermal patches used in EPIT. Patches are being developed to treat peanut, milk and egg allergies.
EPIT starts with a small initial dose that is increased over time by wearing the patch for longer periods of the day, until a maintenance dose is reached in which each patch is worn 24 hours and replaced daily. EPIT using a Viaskin patch does not require physical activity restrictions around dosing and is not disrupted by illness.
Viaskin Peanut has advanced the farthest in EPIT drug development, with the completion of the large, Phase 3 PEPITES clinical trial to test safety and effectiveness in patients with peanut allergy. In July 2020, the Food and Drug Administration (FDA) did not approve DBV Technologies' license application for Viaskin Peanut. The FDA cited concerns regarding patch-site adhesion and indicated the need for patch modifications, to be followed by human study and clinical data generation, as well as submission of additional manufacturing data. The FDA did not raise any safety concerns related to Viaskin Peanut.
Results have also been reported from a small Phase 2 clinical trial testing the safety and effectiveness of Viaskin Milk in treating patients with cow’s milk allergy. Viaskin Egg is in pre-clinical development.
How Effective Is EPIT?
The PEPITES Phase 3 clinical trial of Viaskin Peanut demonstrated a significant response to the peanut patch compared to placebo.
More than 350 peanut-allergic children aged 4-11 participated in PEPITES. For each participant, the dose of peanut protein tolerated after one year of treatment was compared to the dose that triggered reaction symptoms during their initial oral food challenge at the start of the trial. Participants who started treatment reacting to 10 mg peanut protein or less were considered responders if they tolerated 300 mg peanut protein (1 peanut kernel) or more after treatment. Participants who reacted to more than 10 mg but less than 300 mg peanut protein before treatment were considered responders if they tolerated 1 gram peanut protein or more after treatment.
About 35 percent of the Viaskin Peanut group and 14 percent of the peanut-free placebo group responded during the one-year trial. While the proportion of responders differed significantly between the Viaskin Peanut and placebo groups, the high rate of response to placebo meant that the difference in response rates between the treatment and placebo groups was lower than the minimum required to meet the study’s primary endpoint.
The PEPITES study did not reach one part of its primary endpoint, which evaluates the statistical difference between response to the active treatment and response to placebo. However, the study did meet a secondary endpoint: a statistically significant increase in the cumulative reactive dose, which is the total amount of food protein consumed in an oral food challenge before a reaction occurs. Before treatment, for both the treatment and placebo groups, the median (midpoint) cumulative dose consumed prior to reaction was 144 mg peanut protein. After one year of treatment, the median cumulative dose tolerated by children using Viaskin Peanut had increased by a full peanut kernel, to 444 mg peanut protein. In contrast, the median cumulative dose tolerated by children in the placebo group did not change over the year of treatment. This level of peanut tolerance is clinically significant: a recent study reports that raising a patient's tolerance from 100 mg of peanut protein or less to 300 mg of peanut protein lowers the risk of an allergic reaction to cross-contact peanut residue in snack foods by 95 percent.
Announced in January 2020, the PEOPLE study – an open-label (that is, not blinded) extension of the PEPITES study – confirmed that Viaskin Peanut increased peanut tolerance. After three years of using the Viaskin Peanut patch 52 percent of the study population of peanut-allergic children ages 4-11 could consume at least 1,000 milligrams of peanut protein before reacting.
Preliminary results from the Phase II MILES trial for Viaskin Milk have also been reported. Three different daily doses were tested in children aged 2-11 and adolescents aged 12-17. The highest response rate, 58 percent, resulted from treating children for one year with a 300-µg milk patch. By comparison, the response rate of children to placebo patches was 33 percent. Further trials for Viaskin Milk are planned.
How Safe Is EPIT?
Patients generally tolerate EPIT with Viaskin Peanut well, with few patients leaving EPIT studies because of side effects. Adherence rates for daily EPIT dosing are high. Ninety percent of PEPITES participants completed the trial, with active treatment and placebo patients leaving at similar rates. Most participants in both groups experienced mild skin reactions at the patch site, which typically improved as treatment progressed. Of 238 participants in the Viaskin Peanut group, five had serious skin reactions but did not permanently leave the trial as a result. Three Viaskin Peanut group participants experienced four moderate anaphylactic reactions treated with epinephrine. Only 1.7 percent of Viaskin Peanut recipients dropped out as a result of adverse events that occurred only after treatment has started. None of these adverse events or discontinuations involved gastrointestinal symptoms.