AR101 Oral Immunotherapy for Peanut Allergy

Brian P. Vickery, Andrea Vereda, Thomas B Casale, Kirsten Beyer, George Du Toit, Jonathan O'b Hourihane, Stacie M. Jones, Wayne G. Shreffler, Annette Marcantonio, Carsten Bindslev-Jensen, PALISADE Group of Clinical Investigators

Research output: Contribution to journalJournal articleResearchpeer-review

24 Downloads (Pure)

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 .).

Original languageEnglish
JournalThe New England Journal of Medicine
Volume379
Issue number21
Pages (from-to)1991-2001
ISSN0028-4793
DOIs
Publication statusPublished - 22. Nov 2018

Fingerprint

Peanut Hypersensitivity
Placebos
Food
Pharmaceutical Preparations
Proteins
Arachis
Hypersensitivity
Maintenance
Confidence Intervals

Cite this

Vickery, B. P., Vereda, A., Casale, T. B., Beyer, K., Du Toit, G., Hourihane, J. O., ... PALISADE Group of Clinical Investigators (2018). AR101 Oral Immunotherapy for Peanut Allergy. The New England Journal of Medicine, 379(21), 1991-2001. https://doi.org/10.1056/NEJMoa1812856
Vickery, Brian P. ; Vereda, Andrea ; Casale, Thomas B ; Beyer, Kirsten ; Du Toit, George ; Hourihane, Jonathan O'b ; Jones, Stacie M. ; Shreffler, Wayne G. ; Marcantonio, Annette ; Bindslev-Jensen, Carsten ; PALISADE Group of Clinical Investigators. / AR101 Oral Immunotherapy for Peanut Allergy. In: The New England Journal of Medicine. 2018 ; Vol. 379, No. 21. pp. 1991-2001.
@article{78edfb497b6642579e4c3ef93f9d9243,
title = "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 .).",
author = "Vickery, {Brian P.} and Andrea Vereda and Casale, {Thomas B} and Kirsten Beyer and {Du Toit}, George and Hourihane, {Jonathan O'b} and Jones, {Stacie M.} and Shreffler, {Wayne G.} and Annette Marcantonio and Carsten Bindslev-Jensen and {PALISADE Group of Clinical Investigators}",
year = "2018",
month = "11",
day = "22",
doi = "10.1056/NEJMoa1812856",
language = "English",
volume = "379",
pages = "1991--2001",
journal = "The New England Journal of Medicine",
issn = "0028-4793",
publisher = "Massachusetts Medical Society",
number = "21",

}

Vickery, BP, Vereda, A, Casale, TB, Beyer, K, Du Toit, G, Hourihane, JO, Jones, SM, Shreffler, WG, Marcantonio, A, Bindslev-Jensen, C & PALISADE Group of Clinical Investigators 2018, 'AR101 Oral Immunotherapy for Peanut Allergy', The New England Journal of Medicine, vol. 379, no. 21, pp. 1991-2001. https://doi.org/10.1056/NEJMoa1812856

AR101 Oral Immunotherapy for Peanut Allergy. / Vickery, Brian P.; Vereda, Andrea; Casale, Thomas B; Beyer, Kirsten; Du Toit, George; Hourihane, Jonathan O'b; Jones, Stacie M.; Shreffler, Wayne G.; Marcantonio, Annette; Bindslev-Jensen, Carsten; PALISADE Group of Clinical Investigators.

In: The New England Journal of Medicine, Vol. 379, No. 21, 22.11.2018, p. 1991-2001.

Research output: Contribution to journalJournal articleResearchpeer-review

TY - JOUR

T1 - AR101 Oral Immunotherapy for Peanut Allergy

AU - Vickery, Brian P.

AU - Vereda, Andrea

AU - Casale, Thomas B

AU - Beyer, Kirsten

AU - Du Toit, George

AU - Hourihane, Jonathan O'b

AU - Jones, Stacie M.

AU - Shreffler, Wayne G.

AU - Marcantonio, Annette

AU - Bindslev-Jensen, Carsten

AU - PALISADE Group of Clinical Investigators

PY - 2018/11/22

Y1 - 2018/11/22

N2 - 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 .).

AB - 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 .).

U2 - 10.1056/NEJMoa1812856

DO - 10.1056/NEJMoa1812856

M3 - Journal article

C2 - 30449234

VL - 379

SP - 1991

EP - 2001

JO - The New England Journal of Medicine

JF - The New England Journal of Medicine

SN - 0028-4793

IS - 21

ER -

Vickery BP, Vereda A, Casale TB, Beyer K, Du Toit G, Hourihane JO et al. AR101 Oral Immunotherapy for Peanut Allergy. The New England Journal of Medicine. 2018 Nov 22;379(21):1991-2001. https://doi.org/10.1056/NEJMoa1812856