AR101 Oral Immunotherapy for Peanut Allergy.

Abstract

BACKGROUND:

Peanut allergy, for which there are no approved treatment options, affects patients who are at risk for unpredictable and occasionally life-threatening allergic reactions.

METHODS:

In a phase 3 trial, we screened participants 4 to 55 years of age with peanut allergy for allergic dose-limiting symptoms at a challenge dose of 100 mg or less of peanut protein (approximately one third of a peanut kernel) in a double-blind, placebo-controlled food challenge. Participants with an allergic response were randomly assigned, in a 3:1 ratio, to receive AR101 (a peanut-derived investigational biologic oral immunotherapy drug) or placebo in an escalating-dose program. Participants who completed the regimen (i.e., received 300 mg per day of the maintenance regimen for approximately 24 weeks) underwent a double-blind, placebo-controlled food challenge at trial exit. The primary efficacy end point was the proportion of participants 4 to 17 years of age who could ingest a challenge dose of 600 mg or more, without dose-limiting symptoms.

RESULTS:

Of the 551 participants who received AR101 or placebo, 496 were 4 to 17 years of age; of these, 250 of 372 participants (67.2%) who received active treatment, as compared with 5 of 124 participants (4.0%) who received placebo, were able to ingest a dose of 600 mg or more of peanut protein, without dose-limiting symptoms, at the exit food challenge (difference, 63.2 percentage points; 95% confidence interval, 53.0 to 73.3; P<0.001). During the exit food challenge, the maximum severity of symptoms was moderate in 25% of the participants in the active-drug group and 59% of those in the placebo group and severe in 5% and 11%, respectively. Adverse events during the intervention period affected more than 95% of the participants 4 to 17 years of age. A total of 34.7% of the participants in the active-drug group had mild events, as compared with 50.0% of those in the placebo group; 59.7% and 44.4% of the participants, respectively, had events that were graded as moderate, and 4.3% and 0.8%, respectively, had events that were graded as severe. Efficacy was not shown in the participants 18 years of age or older.

CONCLUSIONS:

In this phase 3 trial of oral immunotherapy in children and adolescents who were highly allergic to peanut, treatment with AR101 resulted in higher doses of peanut protein that could be ingested without dose-limiting symptoms and in lower symptom severity during peanut exposure at the exit food challenge than placebo. (Funded by Aimmune Therapeutics; PALISADE ClinicalTrials.gov number, NCT02635776 .).

• Authors: PALISADE Group of Clinical Investigators, Brian P Vickery, Andrea Vereda, Thomas B Casale, Kirsten Beyer, George du Toit, Jonathan O Hourihane, Stacie M Jones, Wayne G Shreffler, Annette Marcantonio, Rezi Zawadzki, Lawrence Sher, Warner W Carr, Stanley Fineman, Leon Greos, Rima Rachid, M Dolores Ibáñez, Stephen Tilles, Amal H Assa’ad, Caroline Nilsson, Ned Rupp, Michael J Welch, Gordon Sussman, Sharon Chinthrajah, Katharina Blumchen, Ellen Sher, Jonathan M Spergel, Frederick E Leickly, Stefan Zielen, Julie Wang, Georgiana M Sanders, Robert A Wood, Amarjit Cheema, Carsten Bindslev-Jensen, Stephanie Leonard, Rita Kachru, Douglas T Johnston, Frank C Hampel Jr, Edwin H Kim, Aikaterini Anagnostou, Jacqueline A Pongracic, Moshe Ben-Shoshan, Hemant P Sharma, Allan Stillerman, Hugh H Windom, William H Yang, Antonella Muraro, José M Zubeldia, Vibha Sharma, Morna J Dorsey, Hey J Chong, Jason Ohayon, J Andrew Bird, Tara F Carr, Dareen Siri, Montserrat Fernández-Rivas, David K Jeong, David M Fleischer, Jay A Lieberman, Anthony E J Dubois, Marina Tsoumani, Christina E Ciaccio, Jay M Portnoy, Lyndon E Mansfield, Stephen B Fritz, Bruce J Lanser, Jonathan Matz, Hanneke N G Oude Elberink, Pooja Varshney, Stephen G Dilly, Daniel C Adelman, A Wesley Burks
• Journal: The New England journal of medicine (N Engl J Med) Vol. 379 Issue 21 Pg. 1991-2001 (Nov 22 2018) ISSN: 1533-4406 [Electronic] United States
• PMID: 30449234 (Publication Type: Clinical Trial, Phase III, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Allergens
• Biological Products
• Plant Proteins

Topics

• Administration, Oral
• Adolescent
• Adult
• Age Factors
• Allergens (administration & dosage, adverse effects)
• Arachis (adverse effects)
• Biological Products (administration & dosage, adverse effects, immunology)
• Child
• Child, Preschool
• Desensitization, Immunologic (adverse effects, methods)
• Dose-Response Relationship, Immunologic
• Double-Blind Method
• Female
• Gastrointestinal Diseases (etiology)
• Humans
• Male
• Middle Aged
• Peanut Hypersensitivity (therapy)
• Plant Proteins (administration & dosage, adverse effects, immunology)
• Young Adult