ANAHEIM, Calif. — A specially formulated toothpaste that’s designed to alleviate peanut allergy via oral mucosal exposure appears to be safe, according to findings from the phase I OMEGA trial.
No severe systemic adverse events and only three moderate local adverse events were reported in the active agent group, reported William Berger, MD, of Children’s Hospital of Orange County in California, during his presentation at the American College of Allergy, Asthma & Immunology annual meeting.
Five adverse events, all mild, required treatment in three patients and may have been related to the therapy: two cases of abdominal pain and single cases of pharyngeal swelling, lip swelling, and gingival swelling.
As for efficacy, an exploratory objective, Berger reported that participants receiving the active agent demonstrated a significant change in serum immunoglobulin (Ig)G4 levels relative to control (P=0.046), and there was a decrease in IgE/IgG4 ratio, which Berger noted were signs of immune response.
“There was a strong foundation established based on a high absolute response rate, favorable risk, ease of use, and adherence,” Berger said. “Immunotherapy is conveniently administered and becomes part of your normal daily routine instead of having to put stuff on yogurt, put stuff on ice cream. All you have to do is get up in the morning or in the evening and just brush your teeth.”
Peanut allergy, which usually lasts for a lifetime, accounts for most of the serious allergic reactions to food worldwide, according to a 2022 report.
In recent years, researchers have explored multiple strategies to deliver immunotherapy and desensitize patients with food allergy. However, the 2022 report noted that “food allergies have been difficult to treat in this way due to high anaphylactic potential and only recently the first immunotherapy for peanut allergy has received regulatory approval.”
Julia Upton, MD, MPH, of the University of Toronto and Hospital For Sick Children, told MedPage Today that researchers are exploring ways to desensitize patients by exposing them to tiny bits of peanut.
“Studies are using the skin as a route of exposure, as in the peanut patch (Palforzia), or by the sublingual route by using small doses under the tongue for a few minutes, which are then ingested,” explained Upton, who was not involved in this study. “There are also studies trying exposure to the lymph nodes and other routes. In the case of oral mucosal immunotherapy [OMIT], it is using the oral mucosa as the route of exposure and then expelling the allergen rather than ingesting it.”
She said the toothpaste strategy is promising, especially since an exploratory analysis showed signs of possible immune system changes. “By exposure to the oral mucosa, there may be the ability for the allergen to shift the response of the immune system. And then by expelling the allergen, there may be the potential to reduce the risk of systemic allergic reactions, such as anaphylaxis, to the food allergen.”
Upton noted that while the peanut protein amount used in the toothpaste was not disclosed, “small doses of peanut protein have been shown to be able to increase the threshold of reaction via multiple routes.”
As for caveats, Upton pointed out that “the abstract did not report if patients rinsed their mouth or not and did not mention if patients needed to have lifestyle modifications of avoiding exercise or certain medications for a few hours after using the toothpaste.”
While she said it’s too early to discuss cost and insurance coverage, it has been reported that the FDA-approved peanut patch treatment “has so far proved a flop,” burdened by its high cost and need for multiple medical appointments.
For the double-blind, placebo-controlled, dose-escalation OMEGA trial, the researchers enrolled 32 patients ages 18 to 55 with peanut allergy as defined by meeting at least one of these conditions: positive skin prick test (wheal at least 3 mm greater than control) and/or peanut-specific IgE >0.35 kU/L, convincing clinical history of allergic reaction to peanut within 1 hour of ingestion for at least 3 months prior to screening, or failure of an oral food challenge of <100 mg of peanut protein at screening.
“Because this was a safety study, we were asked by the regulatory agency not to include patients who are extremely sensitive,” Berger said. “So anybody who had history of severe anaphylaxis is not included in this trial.”
In a 1:3 ratio, participants were assigned to either placebo or the active agent (INT301), a toothpaste instilled with allergenic peanut proteins.
Patients used the active-agent toothpaste 97% of the time versus 99% among those on placebo.
In a statement, Intrommune Therapeutics, the developer of the product, said a full trial dataset should be released next year, and a phase II pediatric trial is in the works.
Intrommune Therapeutics funded the study.
Berger is an Intrommune consultant.
Upton reported receiving institutional grants/research support from DBV Technologies, Sanofi, Regeneron, ALK Abello, Novartis, the Canadian Institutes of Health Research, and the Sick Kids Food Allergy and Anaphylaxis Program; honoraria from Bausch Health, Pfizer, and AstraZeneca; and a mutual confidentiality agreement with Intrommune.
American College of Allergy, Asthma & Immunology
Source Reference: Berger W, et al “A randomized, placebo-controlled phase 1 safety study of OMIT in adults with peanut allergy” ACAAI 2023.