SEATTLE — Peanut powder immunotherapy helps children and adolescents with severe allergies build tolerance to small amounts of peanut, which could protect many of them from accidental exposure, final results from the phase 3 international PALISADE study (NCT02635776) show.
"In this highly allergic population, treatment with AR101 demonstrated clinical desensitization and an acceptable safety profile in children and adolescents," said investigator Stephen Tilles, MD, from the University of Washington in Seattle, who is a consulting adviser for Aimmune Therapeutics, which is developing the oral biologic.
He presented findings from the PALISADE study, which were simultaneously published online in the New England Journal of Medicine, here at the American College of Allergy, Asthma & Immunology (ACAAI) 2018 Annual Scientific Meeting.
This is the first successful phase 3 study in a high-stakes race to offer therapy for a condition that affects about 2% of children in the United States, where peanuts are the leading cause of death among food-induced allergic reactions.
The 551 participants in PALISADE ranged from 4 to 55 years of age, although most were children and adolescents. The trial was conducted at 66 sites in 10 countries in North America and Europe.
During the 12-month study period, 372 peanut-allergic patients were randomly assigned to AR101 immunotherapy in escalating doses until a maintenance dose was reached and 124 were assigned to placebo. Upon completion of the study, participants underwent a double-blind, placebo-controlled food challenge.
"It's the first study to use an independent assessor who was blinded to the subjects, and also the first to include subjects who had a history of severe anaphylaxis," Tilles reported.
Of the 496 participants who were 4 to 17 years of age, more in the immunotherapy group than in the placebo group were able to ingest at least 600 mg of peanut protein (about two peanuts), without dose-limiting symptoms, at the exit challenge (67.2% vs 4.0%; P < .001). At baseline, eligible participants could tolerate no more than 100 mg (about one-third of one peanut).
During the exit challenge, symptoms were less severe in the immunotherapy group than in the placebo group. When maximum severity of symptoms was assessed, fewer participants in the immunotherapy group reached the moderate level (25% vs 59%) and the severe level (5% vs 11%).
In the younger participants, adverse events during the study period, not including the exit challenge, were experienced by 98.7% of the immunotherapy group and by 95.2% of the placebo group.
|Table. Highest Level of Adverse Events Experienced Before the Exit Challenge|
|Group||Mild, %||Moderate, %||Severe, %|
However, about "90% of patients treated with AR101 — even when they had reactions — did not require epinephrine. This is in contrast with placebo, where the majority did receive epinephrine and, in many cases, more than one dose," Tilles reported.
He added that the frequency and severity of allergic reactions were as expected.
None of the adverse effects — which led 10% to 17% of the immunotherapy group and 0.0% to 2.9% of the placebo group to withdraw from the study — were life-threatening.
The treatment had no significant effect on the 55 study participants older than 17 years, the investigators report.
Having a capsule that reliably contains the precise, tiny amount of the peanut immunotherapy needed to desensitize patients is important, Michael Perkin, PhD, from the Population Health Research Institute at St. George's University of London, who was not part of the study, writes in an accompanying editorial.
The lowest-dose capsules of AR101 contain 0.5 mg and 1 mg of the peanut protein, which would be extremely difficult for allergy centers to measure and administer consistently, he points out.
"Desensitization was not easy on the patients," and "is not something to start at home" without a carefully manufactured product, he adds.
Perkin also points out "the longer-term side effects of sustained consumption of an allergen to which the body has produced IgE antibodies remain unknown. Current thinking has focused on eosinophilic disease, such as eosinophilic esophagitis, but surveillance and follow-up will be crucial."
Physicians and families are eagerly waiting for an approved immunotherapy, said ACAAI President Todd Mahr, MD. If the US Food and Drug Administration (FDA) approves AR101, it will be available by prescription.
"Some practitioners are already doing it without the rigor of the hopefully FDA-approved products," Mahr told Medscape Medical News. Such products could lessen the anxiety of parents with young children, he added.
The trial was funded by Aimmune Therapeutics. The PALISADE investigators report receiving fees, grants, and other support from Aimmune Therapeutics, and patents pending on the immunotherapy, as detailed in the published study. Perkin and Mahr have disclosed no relevant financial relationships.
American College of Allergy, Asthma & Immunology (ACAAI) 2018 Annual Scientific Meeting: Abstract A103. Presented November 18, 2018.
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