New study results on the immune profile of healthy human skin across various body areas could have significant implications for the treatment of food allergies and other immunological disorders with epicutaneous immunotherapy (EPIT).
In an oral presentation at the 3rd Inflammatory Skin Disease Summit (ISDS) in Vienna, Austria this week, Dr. Ester Del Duca of the Icahn School of Medicine at Mount Sinai shared the results of a trial showing notable differences in cell type distribution and immune profile of healthy individual’s skin.
Del Duca and team’s investigation assessed 4 locations—inner upper arm, upper back, outer upper thigh, and lower abdomen—for regulation of the T helper cell 2 (Th2) and Th17 pathway genes, plus regulatory T cells. Both markers are critical targets for allergic reaction prevention, according to the investigators.
Of the observed locations of skin, upper back region showed the greatest regulation both Th2/Th17 pathway genes and regulatory T cells, the greatest rate of dendritic and Langerhans cells, and the lowest expression of negative immune regulators. Investigators believe this makes it the region most likely to conduct immune recognition of antigens in allergy patients treated with EPIT.
The findings have particularly crucial implication for DBV Technologies, the France-based biopharmaceutical firm which submitted a Biologics License Application (BLA) to the US Food and Drug Administration (FDA) in October for its EPIT therapy Viaskin Peanut—a pediatric peanut allergy treatment scheduled to receive FDA decision in early 2019.
The investigative patch was designed to deliver a small amount of peanut protein via patients’ backs to the immune-system Langerhans cells, thereby desensitizing patients to peanut allergens. Its application to the FDA is supported by both Breakthrough and Fast Track Designations from the FDA, as well as clinical evidence showing 250 mcg therapy significantly desensitizes peanut allergy in patients aged 4-11 years old versus placebo.
If approved, Viaskin Peanut can be the first FDA-approved therapy for the life-threatening chronic allergy that currently affects about 1.5 million children in the US.
2019 could potentially be a booming year for advancing allergy care. Along with the EPIT skin patch therapy, investigative oral peanut allergen drug AR101 from Aimmune Therapeutics is anticipated to submit an application to the FDA in short time—1 month following a series of promising study results being presented at the American College of Allergy, Asthma & Immunology (ACAAI) annual meeting in Seattle, WA.
In long-term cohort analysis of the phase 3 PALISADES trial, about two-thirds (67.2%) of pediatric peanut allergy patients to receive AR101 300 mg once-daily therapy were capable of ingesting a 600 mg-plus peanut protein without dose-limiting symptoms after about 24 weeks. Among patients to receive placebo, just 4% were capable of the same ingestion (95% CI: 53.0 — 73.3; P < .001).
Another presented trial, centered on assessing the treatment satisfaction for patients and parents included in the PALISADES study, reported that AR101 was mostly favorable in treated patients while also showing positive impacts on their quality of life.
In an interview with MD Magazine®, Princeton, NJ-based internist Simon Murray, MD, noted how burdensome peanut allergies can be for pediatric patients and their families. The amount of “education and diligence” that goes into monitoring the highly dangerous condition makes the development of desensitization therapies all the more critical.
“Should these oral desensitization products turn out to be positive—and it looks like they helped a significant amount of the people during the desensitization process—it could potentially help quite a few people,” Murray said. “It is an exciting breakthrough.”
Regarding the new skin immune profile trial results, Hugh Sampson, MD, chief scientific officer of DBV Technologies and Kurt Hirschhorn Professor of Pediatrics at Icahn emphasized the significance of the back being proven to be the most immunological-responsive area observed by investigators.
“Such data help ensure that novel treatments are optimized in the real-world and further support the therapeutic benefit that children with peanut allergy may receive from treatment with Viaskin Peanut, which is applied directly to the upper back,” Sampson said in a statement.
The study, "Major Differences in Expression of Inflammatory Products in Skin from Different Body Sites of Healthy Individuals," was presented at ISDS 2018.