The Efficacy of AR101, a Peanut-Derived Pharmaceutical for Oral Immunotherapy (OIT), Is Maintained and Tolerability Is Increased with Low-Dose Maintenance Therapy

RationaleAR101, a pharmaceutical for OIT, demonstrated robust efficacy in ARC001, a Phase 2, double-blind, placebo-controlled trial in 4-21 year olds. We now report results from the open-label continuation trial, ARC002.MethodsIn ARC002, former ARC001 placebo subjects up-dosed to 300 mg/d of peanut protein as AR101, then underwent double-blind placebo-controlled food challenge (DBPCFC) after 2 more weeks of therapy. Those passing DBPCFC at 443 mg cumulative of peanut protein, were eligible to continue maintenance therapy for 12 additional weeks. Former AR101 subjects who up-dosed successfully in ARC001 entered ARC002’s 12-week maintenance period directly. As all former ARC001 subjects underwent 12 weeks of open-label maintenance therapy with 300 mg/d AR101 in ARC002, the post-maintenance DBPCFC results from both groups were pooled.ResultsAll 26 ARC001 placebo subjects entered ARC002 and up-dosed over an average of approximately 22 weeks. Of these, 21 reached 300 mg/d AR101 (4 discontinuing from gastrointestinal AEs; 1 for scheduling issues), and 20 passed DBPCFC at 443 mg. Of 29 ARC001 subjects treated with AR101, 23 completed the study and 21 entered ARC002. Of the 40 subjects undergoing post-maintenance DBPCFC, 100%, 90%, and 60% tolerated a cumulative 443, 1043, 2043 mg of peanut protein, respectively. Only 2 subjects required single doses of epinephrine during the DBPCFC. AR101 showed improved tolerability during maintenance versus up-dosing, with reduced AE rates and no treatment-related discontinuations.ConclusionsIn ARC002, twelve weeks of AR101 maintenance at 300 mg/d resulted in 90% desensitization to ≥1043 mg of peanut protein, equivalent to ∼4 peanuts, with improved tolerability. RationaleAR101, a pharmaceutical for OIT, demonstrated robust efficacy in ARC001, a Phase 2, double-blind, placebo-controlled trial in 4-21 year olds. We now report results from the open-label continuation trial, ARC002. AR101, a pharmaceutical for OIT, demonstrated robust efficacy in ARC001, a Phase 2, double-blind, placebo-controlled trial in 4-21 year olds. We now report results from the open-label continuation trial, ARC002. MethodsIn ARC002, former ARC001 placebo subjects up-dosed to 300 mg/d of peanut protein as AR101, then underwent double-blind placebo-controlled food challenge (DBPCFC) after 2 more weeks of therapy. Those passing DBPCFC at 443 mg cumulative of peanut protein, were eligible to continue maintenance therapy for 12 additional weeks. Former AR101 subjects who up-dosed successfully in ARC001 entered ARC002’s 12-week maintenance period directly. As all former ARC001 subjects underwent 12 weeks of open-label maintenance therapy with 300 mg/d AR101 in ARC002, the post-maintenance DBPCFC results from both groups were pooled. In ARC002, former ARC001 placebo subjects up-dosed to 300 mg/d of peanut protein as AR101, then underwent double-blind placebo-controlled food challenge (DBPCFC) after 2 more weeks of therapy. Those passing DBPCFC at 443 mg cumulative of peanut protein, were eligible to continue maintenance therapy for 12 additional weeks. Former AR101 subjects who up-dosed successfully in ARC001 entered ARC002’s 12-week maintenance period directly. As all former ARC001 subjects underwent 12 weeks of open-label maintenance therapy with 300 mg/d AR101 in ARC002, the post-maintenance DBPCFC results from both groups were pooled. ResultsAll 26 ARC001 placebo subjects entered ARC002 and up-dosed over an average of approximately 22 weeks. Of these, 21 reached 300 mg/d AR101 (4 discontinuing from gastrointestinal AEs; 1 for scheduling issues), and 20 passed DBPCFC at 443 mg. Of 29 ARC001 subjects treated with AR101, 23 completed the study and 21 entered ARC002. Of the 40 subjects undergoing post-maintenance DBPCFC, 100%, 90%, and 60% tolerated a cumulative 443, 1043, 2043 mg of peanut protein, respectively. Only 2 subjects required single doses of epinephrine during the DBPCFC. AR101 showed improved tolerability during maintenance versus up-dosing, with reduced AE rates and no treatment-related discontinuations. All 26 ARC001 placebo subjects entered ARC002 and up-dosed over an average of approximately 22 weeks. Of these, 21 reached 300 mg/d AR101 (4 discontinuing from gastrointestinal AEs; 1 for scheduling issues), and 20 passed DBPCFC at 443 mg. Of 29 ARC001 subjects treated with AR101, 23 completed the study and 21 entered ARC002. Of the 40 subjects undergoing post-maintenance DBPCFC, 100%, 90%, and 60% tolerated a cumulative 443, 1043, 2043 mg of peanut protein, respectively. Only 2 subjects required single doses of epinephrine during the DBPCFC. AR101 showed improved tolerability during maintenance versus up-dosing, with reduced AE rates and no treatment-related discontinuations. ConclusionsIn ARC002, twelve weeks of AR101 maintenance at 300 mg/d resulted in 90% desensitization to ≥1043 mg of peanut protein, equivalent to ∼4 peanuts, with improved tolerability. In ARC002, twelve weeks of AR101 maintenance at 300 mg/d resulted in 90% desensitization to ≥1043 mg of peanut protein, equivalent to ∼4 peanuts, with improved tolerability.