Biologic Protects in Case of Accidental Peanut Ingestion

Fran Lowry

March 05, 2018

ORLANDO — The dose of peanut that children with severe peanut allergies were able to tolerate was 100 times higher after oral immunotherapy with AR101, an investigational biologic in the form of peanut powder, according to a new study.

The phase 3 Peanut Allergy Oral Immunotherapy Study of AR101 for Desensitization in Children and Adults (PALISADE) "is the largest pediatric therapeutic study that has been done for peanut allergy, and the results are quite impressive," said lead investigator Stacie Jones, MD, from Arkansas Children's Hospital in Little Rock.

"Sixty-seven percent of the kids who were treated actually could tolerate up to two peanuts in a food challenge, whereas before, they could tolerate less than 10% of a peanut," reported Jones, who is on the scientific advisory board for and receives research support from Aimmune Therapeutics, the sponsor of the study.

"Of the kids who got placebo, only 4% could tolerate that amount, so there was a very high level of tolerability after 1 year of treatment, really indicating the strong possibility for protection against accidental ingestion," she added.

"AR101 is an oral biologic product with the classic and full complement of peanut protein manufactured in accordance with Good Manufacturing Practice specifications," she told Medscape Medical News.

The study population was comprised of peanut-allergic patients 4 to 55 years of age; however, Jones presented data on a prespecified primary analysis of participants 4 to 17 years of age here at the American Academy of Allergy, Asthma and Immunology and World Allergy Organization 2018 Joint Congress.


Of the 496 children, 372 were randomly assigned to receive AR101 and 124 to receive placebo.

Of this cohort, 57% was male and 78% was white, "as is often seen in food-allergy trials," Jones pointed out. In addition, 72% had a history of anaphylaxis to peanut, more than one-half had asthma, and two-thirds had multiple food allergies.

At baseline, the mean skin-prick wheal test size was 11 mm, mean peanut-specific immunoglobulin (Ig) E was 71 IU/mL, and all participants reacted to less than 100 mg of peanut protein in a double-blind, placebo-controlled food challenge.

"In other words, these participants could tolerate no more than 30 mg, or about one-tenth of a peanut, at baseline. Only the most sensitive went on to the up-dosing phase," Jones said.

People with recurrent or chronic gastrointestinal symptoms of any cause, severe or poorly controlled asthma, or severe anaphylaxis in the 60 days before enrolment were excluded from the study. Prophylactic use of symptomatic therapies, such as antihistamines, was prohibited throughout the study to prevent the masking of symptoms.

At study entry, participants began a 2-week dose-escalation phase, which started with 3 mg and increased to 300 mg. The dose was escalated every 2 weeks, so the children remained at each dose level for 2 weeks.

When participants reached 300 mg, they entered the 6-month maintenance phase of the study. After 6 months of maintenance, the children underwent a food challenge test conducted by an investigator who had no previous contact with the study participant.

Of the 496 patients who entered the study, 412 completed the trial.

An intent-to-treat analysis showed that the primary end point — the consumption of 600 mg of peanut protein during the exit challenge — was met by more people in the AR101 group than in the placebo group (67% vs 4%).

Table. Peanut Protein Tolerated at the Exit Challenge

Level Tolerated AR101 Group, % Placebo Group, %
300 mg 77 8
1000 mg 50 2


People in the AR101 group developed fewer moderate and severe symptoms than those in the placebo group, required more peanut exposure to elicit the onset of symptoms, were more likely to complete the challenge, and needed less epinephrine.

Adverse Events

There were more serious adverse events in the AR101 group than in the placebo group (8 vs 1). Five people in the AR101 group dropped out of the study because of a serious adverse event.

One of the four serious adverse events related to the study drug was severe. "This occurred in a 16-year-old girl who suffered anaphylaxis early on in the maintenance phase. She had very high baseline IgE," Jones explained.

There were no deaths, life-threatening adverse events, or suspected unexpected serious adverse reactions.

In the AR101 group, 16 people discontinued therapy because of gastrointestinal events, a common complaint, and 54 developed treatment-emergent systemic hypersensitivity reaction (most mild or moderate), leading 10 to discontinue treatment.

Two of the systemic reactions that occurred during dose escalation were attributed to AR101.

This is an extremely important study, said PALISADE investigator Thomas Casale, MD, from the University of South Florida in Tampa.

"These extremely sensitized kids were able to tolerate about a 100-fold greater dose of peanut at the end of the study," he told Medscape Medical News. "That equates to only about three or four peanuts, so they can't go out and eat a bag of peanuts, but it is going to protect them from accidental exposure."

As somebody who treats food allergy exclusively, I think this is a viable option. I hope this gets approved as soon as possible.

"This is a fabulous study with fantastic results; they turned out better than any of us expected. This really works," said Matthew Greenhawt, MD, from Children's Hospital Colorado in Aurora, who was not involved in the study.

"Oral immunotherapy has always shown promise, and we've seen in each iteration of each study that it's gotten safer and safer, with more people benefiting," he explained.

For this study, "they took a good long look at everything out there, they understood what parents' goals were, and they picked a nice sweet spot where it can be done safely," Greenhawt added. "This will be one of those moments in food allergy where we can say we truly have something that we can treat these kids with. As somebody who treats food allergy exclusively, I think this is a viable option. I hope this gets approved as soon as possible."

This study was sponsored by Aimmune Therapeutics. Jones reports that she is on the scientific advisory board of and receives research funding from Aimmune Therapeutics. Greenhawt has disclosed no relevant financial relationships.

American Academy of Allergy, Asthma and Immunology (AAAAI) and World Allergy Organization (WAO) 2018 Joint Congress: Abstract L6. Presented March 4, 2018.

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