Open-label follow-on study evaluating the efficacy, safety, and quality of life with extended daily oral immunotherapy in children with peanut allergy

Montserrat Fernandez-Rivas, Andrea Vereda, Brian P Vickery, Vibha Sharma, Caroline Nilsson, Antonella Muraro, Jonathan O'B Hourihane, Audrey DunnGalvin, George du Toit, Katharina Blumchen, Kirsten Beyer, Alex Smith, Robert Ryan, Daniel C Adelman, Stacie M Jones, Montserrat Fernandez-Rivas, Andrea Vereda, Brian P Vickery, Vibha Sharma, Caroline Nilsson, Antonella Muraro, Jonathan O'B Hourihane, Audrey DunnGalvin, George du Toit, Katharina Blumchen, Kirsten Beyer, Alex Smith, Robert Ryan, Daniel C Adelman, Stacie M Jones

Abstract

Background: The benefit of daily administration of Peanut (Arachis hypogaea) Allergen Powder-dnfp (PTAH)-formerly AR101-has been established in clinical trials, but limited data past the first year of treatment are available. This longitudinal analysis aimed to explore the impact of continued PTAH therapeutic maintenance dosing (300 mg/day) on efficacy, safety/tolerability, and food allergy-related quality of life.

Methods: We present a subset analysis of PALISADE-ARC004 participants (aged 4-17 years) who received 300 mg PTAH daily for a total of ~1.5 (Group A, n = 110) or ~2 years (Group B, n = 32). Safety assessments included monitoring the incidence of adverse events (AEs), accidental exposures to food allergens, and adrenaline use. Efficacy was assessed by double-blind, placebo-controlled food challenge (DBPCFC); skin prick testing; peanut-specific antibody assays; and Food Allergy Quality of Life Questionnaire (FAQLQ) and Food Allergy Independent Measure (FAIM) scores.

Results: Continued maintenance with PTAH increased participants' ability to tolerate peanut protein: 48.1% of completers in Group A (n = 50/104) and 80.8% in Group B (n = 21/26) tolerated 2000 mg peanut protein at exit DBPCFC without dose-limiting symptoms. Immune biomarkers showed a pattern consistent with treatment-induced desensitization. Among PTAH-continuing participants, the overall and treatment-related exposure-adjusted AE rate decreased throughout the intervention period in both groups. Clinically meaningful improvements in FAQLQ and FAIM scores over time suggest a potential link between increased desensitization as determined by the DBPCFC and improved quality of life.

Conclusions: These results demonstrate that daily PTAH treatment for peanut allergy beyond 1 year leads to an improved safety/tolerability profile and continued clinical and immunological response.

Trial registration: ClinicalTrials.gov NCT03201003 NCT02635776 NCT03292484.

Keywords: desensitization; food allergy; oral immunotherapy; peanut allergy; quality of life.

Conflict of interest statement

Montserrat Fernández‐Rivas reports consultancies for Aimmune Therapeutics, DBV, Novartis, SPRIM; research funding from European Commission, MINECO and ISCIII of Spanish government; speakers bureau for ALK, Allergy Therapeutics, Diater, Fundacion SEAIC, GSK, HAL Allergy, Thermo Fisher Scientific. Andrea Vereda is an employee and stockholder of Aimmune Therapeutics. Brian P Vickery reports advisory board/consultant: Aimmune Therapeutics, AllerGenis, FARE, Reacta; site investigator: Aimmune Therapeutics, DBV, Genentech, Regeneron; research grants: FARE, NIAID. Vibha Sharma reports speaker fees from Aimmune Therapeutics outside the submitted work. Caroline Nilsson reports grants to institution and advisory board fees from Aimmune Therapeutics and Novartis and speakers fees from MEDA, ALK, Thermo Fisher, GSK. Antonella Muraro reports personal fees from DVB Technologies, Aimmune, Nestlé‐Purina, Nestlé Health Institute, Mylan, and Nutricia outside the submitted work. Jonathan O'B. Hourihane reports advisory board fees, Aimmune Therapeutics; speakers bureau, Aimmune Therapeutics, DBV Technologies, Nutricia, Mead Johnson; grants to institution/research funding, and clinical trials within past 2 years, Aimmune Therapeutics, DBV Technologies. Audrey DunnGalvin reports personal fees from Aimmune Therapeutics and DBV Technologies outside the submitted work. George du Toit reports research grants to institution and advisory board fees from Aimmune Therapeutics. Katharina Blumchen reports consulting for Aimmune Therapeutics, DBV Technologies, Bencard Allergie, HAL Allergy; speakers bureau for Aimmune Therapeutics, DBV Technologies, HAL Allergy, Nutricia, Thermo Fisher Scientific, ALK, Allergopharma, Nestle; and conducting clinical trials for Aimmune Therapeutics, DBV Technologies, and Hipp. Kirsten Beyer reports advisory board/consulting fees from Aimmune Therapeutics, ALK, Bausch & Lomb, Bencard, Danone, DBV, Hycor, Infectopharm, Mabylon, Meda Pharma, Mylan, Nestle; speakers bureau for Aimmune Therapeutics, Allergopharma, Bencard, Danone, Di‐Text, Hammer und Rall Media, Infectopharm, Meda Pharma, Med Update, Nestle, Nutricia; and research grants from Aimmune, ALK, Danone, DBV, Good Mills, Hipp, Hycor, Infectopharm, Nutricia, ThermoFisher, VDI. Alex Smith is an employee and stockholder of Aimmune Therapeutics. Robert Ryan an employee and stockholder of Aimmune Therapeutics. Daniel C. Adelman was an employee and stockholder of Aimmune Therapeutics at the time of the development of this work. He has patents pending for the following: US 16/542,198; PCT/US2019/046706; US 16/721,805; PCT/US2019/067634. Stacie M. Jones reports advisory board fees, Aimmune Therapeutics, FARE; personal fees, DBV Technologies; clinical trials grants, Aimmune Therapeutics, DBV Technologies, Astellas, Sanofi, Regeneron, FARE, Genentech, and NIH‐NIAID.

© 2021 Aimmune Therapeutics. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.

Figures

FIGURE 1
FIGURE 1
Treatment protocol. *Group A in this analysis was ARC004 Cohort 1 which continued daily PTAH treatment for an additional 28 weeks. Participants in Group B of this analysis were randomly assigned to daily PTAH treatment for an additional 56 weeks in ARC004 (Cohort 3a). Cohorts 2, 3B, and 3C represented the non‐daily dosing cohorts. Cohort 2 initially received 300 mg every other day (4 weeks) and then 300 mg 138 twice weekly (24 weeks). Cohorts 3B and 3C initially received daily doses of 300 mg (28 weeks), followed by 300 mg every other day (4 weeks), and 300 mg twice weekly (duration of twice‐weekly treatment varied). Cohorts 2, 3B, and 3C are not discussed further in this paper. DBPCFC, double‐blind, placebo‐controlled food challenge; FAIM, Food Allergy Independent Measure; FAQLQ, Food Allergy Quality of Life Questionnaire; y, years
FIGURE 2
FIGURE 2
Efficacy of Continued PTAH Therapeutic Maintenance Dosing: Tolerated Doses at Exit DBPCFC in Group A and Group B (Completer Population). DBPCFC, double‐blind, placebo‐controlled food challenge; ITT, intent‐to‐treat
FIGURE 3
FIGURE 3
Changes in (A) psIgE levels, (B) psIgG4levels, (C) psIgE/IgG4 ratio (D) peanut SPT mean wheal diameter between baseline, end of updosing, and exit during PALISADE and ARC004 (Completer Population). IgE, immunoglobulin E; IgG4, immunoglobulin G4; ps, peanut‐specific; SD, standard deviation, SPT, skin prick test
FIGURE 4
FIGURE 4
FAQLQ total score at PALISADE baseline, PALISADE exit, and ARC004 exit for (A) Group A and (B) Group B. CI, confidence interval; FAQLQ, Food Allergy Quality of Life Questionnaire; y, years
FIGURE 5
FIGURE 5
Percentages of participants whose FAQLQ total score changed (≥0.5) from PALISADE screening to PALISADE exit and ARC004 exit. (A) Children (aged 8–12 years, self‐report), teenagers (aged 13–17 years, self‐report), caregivers of children (aged 7–12 years, proxy‐report) and teenagers (aged 13–17 years, proxy‐report) in Group A. (B) Children (aged 8–12 years, self‐report), teenagers (aged 13–17 years, self‐report), caregivers of children (aged 7–12 years, proxy‐report), and teenagers (aged 13–17 years, proxy‐report) in Group B. FAQLQ, Food Allergy Quality of Life Questionnaire; y, years

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