Peanut Allergy Tablet Boosts Tolerance in Study, Heads to Phase 3

A tablet placed under the tongue increased peanut tolerance in about half of allergic children and adults after six months of daily treatment.

Known as sublingual immunotherapy, or SLIT, the rapidly dissolving tablet contains a small amount of peanut allergen. Based on the positive Phase 2 results, the pharmaceutical company ALK plans to launch a Phase 3 trial in late 2026.

In the Phase 2 trial, 150 participants ages 4 to 65 years with peanut allergy were assigned to receive either a low-dose tablet, a high-dose tablet or a placebo.

Participants completed an eight-week dose escalation period, followed by 24 weeks of maintenance therapy. They then underwent a supervised food challenge to determine how much peanut protein they could tolerate before experiencing allergic symptoms.

About 49 percent of participants who received the higher-dose tablet tolerated at least 300 milligrams (mg) of peanut protein compared with 18 percent of those receiving the placebo. (One peanut kernel contains about 250 to 300 mg.)

Some could tolerate more. About 31 percent tolerated at least 600 mg of peanut protein, compared with 8 percent of placebo recipients. About 22 percent taking the higher-dose tablet tolerated 1,000 mg versus 2 percent of those who received the placebo.

The tablet now heads to a Phase 3 trial, pending discussions with regulators, said ALK president and CEO Peter Halling.

“We are beginning to see the contours of an effective, safe, and convenient medicine that may become an important treatment option for patients whose life is profoundly impacted by the disease,” Halling said.

Earlier SLIT Peanut Research

Both the Phase 2 and Phase 3 trial are being led by Dr. Edwin Kim, division chief of Pediatric Allergy and Immunology at the University of North Carolina (UNC) at Chapel Hill. When ALK asked Kim to lead the clinical trial program, he was thrilled.

Kim became intrigued by SLIT in the early 2000s, when sublingual liquid allergen extracts to treat environmental allergies such as pollen were becoming popular in Europe. Side effects were generally mild, mainly consisting of temporary mouth or throat itching. Kim wondered if a similar approach could be used to treat food allergy.

At UNC, he has led several studies with SLIT to treat peanut allergy in children. One study, using SLIT in the form of liquid drops, showed particular promise in the youngest patients. Fourteen of 19 peanut-allergic toddlers who received SLIT for three years could eat 4,443 mg of peanut protein – equivalent to 16 peanuts – without symptoms.

The findings provided strong evidence that SLIT could be both safe and effective, Kim says. “We see a lot of promise,” Kim says.

But he knew that larger, multi-center trials would be needed for the Food and Drug Administration to consider approving a new treatment. That’s what he hopes the Phase 3 trial with the ALK tablet will deliver.

“Where I see the biggest value from the tablet approach is that it’s scalable,” he says. “It’s very easy for me to imagine that you could order it at any clinic, not just food allergy clinics. You wouldn’t have to be a super savvy food allergy parent to administer it.”

Peanut Tablet’s Potential Advantages

Dr. Edwin Kim: SLIT tablet dissolves in seconds.

According to ALK, the tablet contains peanut with standardized amounts of the major allergens, Ara h 1, 2, 3, 6. (Fish gelatin is a non-active ingredient. However, Kim says the gelatin doesn’t contain fish protein and should be safe for people with fish allergy.)

The tablet is shelf stable and doesn’t require refrigeration. It sticks to the moist tissue beneath the tongue, dissolves within seconds, and doesn’t taste like peanut, Kim says.

The Phase 2 study, which was conducted at 40 sites in the U.S. and Canada, found no treatment-related anaphylaxis. Adverse reactions were mostly mild and few participants dropped out because of side effects.

Overall, about 65 percent of patients receiving the higher-dose tablet met the study’s definition of a responder. Responders were patients who reacted to less than 30 mg of peanut at the start of the study and could tolerate at least 300 mg after six months of maintenance treatment. Or, patients who could tolerate up to 100 mg at baseline and could tolerate at least 600 mg after six months on maintenance.

Halling said the peanut tablet demonstrated effectiveness across a broad age range, including adults up to age 65. This population has been under-represented in previous food allergy immunotherapy studies.

SLIT: from Pollen to Peanut Allergy

ALK already markets FDA-approved SLIT tablets for environmental allergens. These include Odactra for dust mites, Grastek for grass pollen allergy, and Ragwitek for ragweed pollen allergy.

“This is the first time ever that we see a strong proof of concept with our tablet technology in food allergy,” Halling said.

Kim believes one of the SLIT tablet’s biggest advantages is its simplicity. Oral immunotherapy (OIT) is very effective at desensitizing to food allergen. In OIT, individuals eat gradually increasing amounts of their allergen over the course of several months to build tolerance.

But OIT is demanding. Treatment requires numerous clinic visits, and reactions are common, particularly during updosing. Sublingual oral immunotherapy with a tablet should require fewer visits, and there is no rest period after dosing.

Still, Kim acknowledges, “the maximum treatment benefit threshold is likely to be lower with sublingual immunotherapy than with oral immunotherapy.”

“But the tradeoff is a much, much lower chance of allergic reactions as well as anaphylaxis, and it’s much, much simpler to do,” he says.

As with other forms of immunotherapy, effectiveness is expected to improve with longer time on treatment, Kim says. That pattern has been observed with OIT and the Viaskin peanut patch, which is being developed by DBV Therapeutics.

The Phase 3 study will likely last one year. “To see a signal in just six months was great,” Kim says. “As long as it follows the pattern of all other immunotherapies, one year will be better, and Year 2, better still.”