AR101 Oral Immunotherapy for Peanut Allergy

Author: Vickery, B.P.; Vereda, A.; Casale, T.B.; Beyer, K.; du Toit, G.; Hourihane, J.O.; Jones, S.M.; Shreffler, W.G.; Marcantonio, A.; Zawadzki, R.; Sher, L.; Carr, W.W.; Fineman, S.; Greos, L.; Rachid, R.; Ibanez, M.D.; Tilles, S.; Assa’ad, A.H.; Nilsson, C.; Rupp, N.; Welch, M.J.; Sussman, G.; Chinthrajah, S.; Blumchen, K.; Sher, E.; Spergel, J.M.; Leickly, F.E.; Zielen, S.; Wang, J.; Sanders, G.M.; Wood, R.A.; Cheema, A.; Bindslev-Jensen, C.; Leonard, S.; Kachru, R.; Johnston, D.T.; Hampel, F.C.J.; Kim, E.H.; Anagnostou, A.; Pongracic, J.A.; Ben-Shoshan, M.; Sharma, H.P.; Stillerman, A.; Windom, H.H.; Yang, W.H.; Muraro, A.; Zubeldia, J.M.; Sharma, V.; Dorsey, M.J.; Chong, H.J.; Ohayon, J.; Bird, J.A.; Carr, T.F.; Siri, D.; Fernandez-Rivas, M.; Jeong, D.K.; Fleischer, D.M.; Lieberman, J.A.; Dubois, A.E.J.; Tsoumani, M.; Ciaccio, C.E.; Portnoy, J.M.; Mansfield, L.E.; Fritz, S.B.; Lanser, B.J.; Matz, J.; Oude Elberink, H.N.G.; Varshney, P.; Dilly, S.G.; Adelman, D.C.; Burks, A.W.

Description: 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 number, NCT02635776 .).

Subject Headings: 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

Keywords: AR101 Oral Immunotherapy for Peanut Allergy

Publication year: 2018

Journal or book title: The New England Journal of Medicine

Volume: 379

Issue: 21

Pages: 1991-2001

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Type: Journal Article

Serial number: 2393