Results showed a statistically significant difference in responder rate between active treatment and placebo but didn’t meet a prespecified threshold for clinical significance.
David Fleischer, MD
A phase 3 trial of Viaskin Peanut, a patch that exposes the skin to micrograms of peanut protein, found that there was a statistically significant 21.7% difference in responders between peanut-allergic children treated with the patch versus placebo.
However, the study did not meet a predefined threshold of ≥15% on the lower bound of a 95% Confidence Interval around the difference in responder rate.
The research, which was published in JAMA and will be presented at the 2019 Annual Meeting of the American Academy of Allergy, Asthma & Immunology (AAAAI), supports the epicutaneous immunotherapy treatment as “convenient and well-tolerated” according to David Fleischer, MD, Director, Allergy and Immunology Center and Associate Section Head, Children’s Hospital Colorado.
“My peanut-allergic patients and their families face the daily fear of accidental peanut exposure resulting in a possible life-threatening reaction, and desperately seek a well-tolerated treatment that does not add even more restrictions to their everyday lives,” said Fleischer, who is the lead author of the publication, in a statement.
The trial included 356 children with peanut allergies between the ages of 4 and 11 years (median age 7 years). Participants were randomized to either daily treatment with the Viaskin Peanut patch containing 250 μg of peanut protein (n = 238) or a placebo patch (n = 118) for 12 months.
The children participated in a food challenge at baseline and at 12 months to determine the change in their eliciting dose—the “highest dose at which objective signs/symptoms of an immediate hypersensitivity reaction developed” wrote the investigators. Responders were defined as those with a baseline eliciting dose of 10 mg or less that increased to 300 mg or more after treatment, or those with a baseline eliciting dose of over 10 mg to 300 mg that increased to 1000 mg or more. There were 61 children in the low—eliciting dose subgroup and 295 children in the high–eliciting dose subgroup.
The overall mean adherence rate was 98.5% (SD 4.3) and 89.9% of participants completed the trial.
The responder rate for the active treatment arm was 35.3% (n = 84) compared to 13.6% (n = 16) in the placebo arm (difference, 21.7% [95% CI, 12.4%-29.8%; P <.001]). That lower bound of the 95% Confidence Interval did not meet the ≥15% criterion for clinical significance that is recommended by the US Food and Drug Administration (FDA) and was agreed to by the trial sponsor.
In an editorial on the study, Jody W. Zylke, MD, Deputy Editor of JAMA, posed the question of how clinicians should handle these results.
“Clinicians will have to determine with patients whether a response of 35.3% with the peanut patch is worthwhile,” Zylke wrote, adding that considerations might include adverse events and adherence related to the patch, as well as a comparison of the patch to other immunotherapy options, such as oral delivery.
For ethical and safety reasons, children with a history severe anaphylaxis in response to peanut exposure, though not any history of anaphylaxis, were excluded from the trial. Severe anaphylaxis was defined as hypotension requiring vasopressor support, hypoxia requiring mechanical ventilation, or neurological compromise. Children with unstable chronic conditions, such as asthma, were also excluded.
The treatment-emergent adverse events (TEAEs) were common in both groups, with an incidence of 95.4% in the peanut-patch group and 89% in the placebo-patch group. The most common TEAEs were application site reactions, including pruritus (peanut patch: 34.5%; placebo patch: 11.9%), erythema (peanut patch: 28.2%; placebo patch: 16.9%), and site swelling (peanut patch: 16%; placebo patch: 1.7%).
There were 4 TEAEs that led to discontinuation, all in the peanut patch group (1.1% overall, 1.7% of active treatment group). Discontinuation due to all causes was 10.5% in the peanut-patch group compared to 9.3% in the placebo group.
Serious TEAEs outside of food challenges occurred in 10 (4.2%) in the peanut-patch group and 6 (5.1%) in the placebo-patch group. There were 26 cases of anaphylaxis, none severe, in 23 participants, of which 10 were determined to be treatment-related to some degree.
“Viaskin Peanut is the first and only epicutaneous immunotherapy in development today for the treatment of peanut allergy. It aims to rebalance the immune system of peanut-allergic patients by exposing them once daily to only about one-one thousandth of a peanut kernel via a non-invasive patch,” said Hugh Sampson, MD, Chief Scientific Officer and interim Chief Medical Officer of DBV Technologies and Kurt Hirschhorn Professor of Pediatrics at the Icahn School of Medicine at Mount Sinai.
Sampson added that the company intends to submit an updated Biologics License Application (BLA) for Viaskin Peanut to the FDA in the third quarter of 2019.
The study, “Effect of Epicutaneous Immunotherapy vs Placebo on Reaction to Peanut Protein Ingestion Among Children With Peanut Allergy: The PEPITES Randomized Clinical Trial,” was published in JAMA. Data from PEPITES will also be presented at the Annual Meeting of AAAAI.