Peanut Sublingual Immunotherapy Study Reports Improved Tolerance, Favorable Safety in Children

As the food allergy community awaits Food and Drug Administration approval of two possible treatments for peanut allergy – Aimmune’s AR101 peanut oral immunotherapy product and DBV’s Viaskin Peanut patch for epicutaneous (“on the skin”) immunotherapy – a third approach to peanut allergy treatment made news this week.

A small phase 2 clinical trial by researchers at the University of North Carolina (UNC) found that about two-thirds of peanut-allergic children who received daily doses of dissolved peanut protein under the tongue were able to tolerate eating about 2.5 peanut kernels after several years of treatment. Funded in part by FARE and published in the Journal of Allergy and Clinical Immunology, the study investigated the safety and effectiveness of extended peanut sublingual immunotherapy, or SLIT, in children ages 1 to 11.

In peanut SLIT, drops of liquid containing small amounts of dissolved peanut protein are placed under the tongue, where they are absorbed. This introduces undigested peanut allergens to cells in the lining of the mouth that promote food tolerance. Allergen immunotherapy with SLIT follows the same dosing pattern as oral immunotherapy (OIT): in both approaches, patients consume daily doses of allergen, starting with small amounts and increasing to a maintenance dose. However, SLIT doses are much smaller and contain much less protein than OIT doses. For example, the PALISADE trial of the peanut OIT product AR101 used a maintenance dose of 300 mg peanut protein, roughly equal to a peanut kernel, while the maintenance dose for the UNC SLIT trial was only 2 mg peanut protein.

The UNC trial suggests that, in children, extended treatment with peanut SLIT may as effective as a year of peanut OIT with AR101, although the number of SLIT participants to date has been much smaller. In the PALISADE AR101 trial, which gave peanut OIT to about 370 children ages 4 to 17, 67 percent of those who started active treatment and 85 percent of those who completed it were able to eat at least 600 mg peanut protein – roughly two peanut kernels – in an oral food challenge. Likewise, of the UNC trial’s 48 participants, 67 percent of those who enrolled and 87 percent of those who received three to five years of peanut SLIT were able to tolerate eating at least 750 mg peanut protein.

Peanut SLIT was well-tolerated, resulting in fewer and milder adverse reactions than AR101 OIT. Itchy mouth and throat were the most common symptoms of peanut SLIT, with less than 0.25 percent of doses requiring antihistamines and none requiring epinephrine. Gastrointestinal symptoms caused two participants (4 percent) to withdraw from the study. By comparison, 13 percent of active OIT participants in the PALISADE trial left treatment because of gut symptoms and other adverse events, including seven instances of anaphylaxis, one of which was severe.

Compared to another peanut allergy treatment – epicutaneous immunotherapy, or EPIT, with Viaskin Peanut (the “peanut patch”) – peanut SLIT was more effective in inducing tolerance. Only 35 percent of about 240 participants ages 4 to 11 who received active treatment with Viaskin Peanut in the PEPITES trial responded to EPIT, as measured by improvements in the amount of peanut tolerated relative to the participant’s baseline tolerance at the start of the trial. 

While these UNC peanut SLIT findings are promising, more and larger studies are needed to better assess the treatment’s effectiveness and safety profile. Researchers hope to demonstrate that multiple years of peanut SLIT can protect against accidental peanut exposure with minimal risk of adverse effects. To learn more about peanut SLIT, watch a brief interview with the UNC study’s lead author, Dr. Edwin Kim (credit: Jonathan Rodriguez, UNC REX Healthcare).