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SEATTLE -- Oral immunotherapy with a standardized 12% defatted peanut flour preparation (AR101) was associated with a significant improvement in peanut tolerance, researchers reported here.

In the phase III PALISADE trial involving close to 500 children and teens, along with just over 50 adults, and after 1 year of treatment, two-thirds of participants, ages 4-17 years, in the active-treatment arm who remained in the study could consume a cumulative dose of approximately three to four peanuts without symptoms versus less than half a peanut before treatments, according to Brian P. Vickery, MD, of Emory University School of Medicine in Atlanta, and colleagues in the PALISADE Group of Clinical Investigators.

At 1 year, just one in 25 study participants in the control arm of the study could consume the equivalent of three to four peanuts without symptoms, they reported at the the American College of Allergy, Asthma, and Immunology (ACAAI) annual scientific meeting and simultaneously in the

Side effects that led to withdrawal from the study occurred in 11.6% of participants in the active treatment arm and 2.4% of participants in the control arm. Also, 14% of those in the active-drug group required epinephrine at some point during treatment.

PALISADE Details

AR101 is a peanut-derived, oral biologic drug that delivers a target daily maintenance dose of 300 mg of peanut protein.

The PALISADE trial was conducted at 66 sites in North America and Europe. Oral immunotherapy (OIT) was delivered in escalating doses, with updosing occurring approximately every 2 weeks for a minimum of 20 weeks, said co-author Stephen Tilles, MD, of Northwest Asthma & Allergy in Seattle. Updosing was performed in the physician's office followed by a period of observation.

Study participants in the active arm who completed the regimen (300 mg per day of maintenance drug for approximately 24 weeks) underwent a double-blind, placebo-controlled exit food challenge.

Of the 496 study participants (ages 4-17 years), 250 of 372 in the active treatment arm (67.2%) successfully ingested 600 mg or more of peanut protein at exit challenge without symptoms versus five of 124 (4%) participants in the placebo arm (difference 63.2%, 95% CI, 53-73.3, P<0.001).

Reactions characterized as having the highest severity of mild were seen in 34.7% of participants in the active treatment group; 59.7% had events with a highest severity characterized as moderate versus 50% and 44.4%, respectively, in the placebo group.

Severe reactions were reported in 4.3% of active-drug participants and 0.8% of the placebo group.

Epinephrine was administered to 52 participants in the active treatment group during the trial (14%) and eight (6.5%) participants in the placebo group.

Efficacy was not shown in the participants who were ages ≥17 years, but only 20 of 42 in this age group in the active treatment arm completed the trial.

Tilles told 麻豆传媒 that the side effect profile and efficacy seen in PALISADE was better than anticipated.

Overall, 67% of participants (ages 4-17 years) in the active arm could tolerate a single dose of at least 600 mg of peanut protein during the exit food challenge. Before treatment, none could tolerate no more than 30 mg of peanut protein without symptoms, which was the equivalent of one-tenth of a peanut.

Half the participants (ages ≤17 years) in the active treatment group tolerated the final exit challenge dose of 1,000 mg, which was the equivalent of three or four peanut kernels.

"For the children in the study who did well, this was life changing," Tilles said. "They still had to do the maintenance treatment, but for them accidental exposure was no longer an issue. They could go to sleepovers or church potlucks without having to worry about exposure."

The study had limitations including the fact that participants were selected on the basis of a sensitivity to a maximum of 100 mg of peanut protein, so may not have represented the entire population of people with peanut allergies, half of whom have reactions to doses >100 mg, the authors pointed out.

Unresolved Concern

In an accompanying editorial, Michael R. Perkin, PhD, of the University of London Population Health Research Institute, wrote that the major unresolved concern regarding peanut allergy immunotherapy is that "allergen tolerance that is induced will be temporary and lost if regular consumption ceases."

"Neither the, nor the investigators in this trial, have attempted to establish the duration for which allergen tolerance is maintained in the absence of ongoing consumption...sustained, potentially lifelong, regular consumption may be needed to maintain allergen tolerance," he stated.

Richard Wasserman, MD, of the Dallas Food Allergy Center, commented that he has treated >800 food allergic children using OIT, including around 325 who were allergic to peanuts.

Asked at an ACAAI session on OIT if he would be switching patients to FDA-approved, commercially available products, Wasserman said he could not think of a patient he has treated that "would be most appropriately treated that way."

He told 麻豆传媒 that he has had no problem achieving adequate dosing with peanut foods such as peanut flour, peanut butter, and whole peanuts, which are certain to be less expensive than drug OIT therapies.

"I have no problem with FDA trials or FDA approvals," he said. "But at this point, there are probably 10 times more patients that have been treated with private practice [real food] OIT. I can treat about 400 patients, and the total peanut cost is about $5.99. We have no idea what these immunotherapies will cost."

Aimmune Therapeutics received Fast Track and Breakthrough Designation status for AR101 from the FDA. Pending FDA approval, it could be on the market as soon as this time next year, a company spokesman told 麻豆传媒.

The biopharmaceutical company DBV Technologies also recently submitted a Biologics License Application (BLA) to the FDA for its peanut immunotherapy patch Viaskin Peanut. Another company is currently conducting trials with another oral immunotherapy (CA002).