OBJECTIVES: AR101 is an investigational oral immunotherapy (OIT) for the treatment of peanut allergy. Results from the phase III PALISADE trial demonstrated that a significantly higher percentage of AR101-treated subjects tolerated higher doses of peanut protein after one year of therapy compared to placebo. However, the benefit of AR101 in reducing anaphylactic reaction (AR) risk after accidental exposure has not been studied. This study aimed to estimate the reduction in accidental exposure related AR risk associated with AR101 using PALISADE data.

METHODS: Parametric interval-censoring survival analysis with maximum likelihood estimation was used to construct a real-world distribution of peanut protein exposure using baseline AR history and maximum tolerated dose (MTD) from a double-blind, placebo-controlled food challenge. The AR risk reduction was estimated using exposure distribution, and MTD assessed at both baseline and trial exit for AR101- and placebo-treated subjects, respectively.

RESULTS: Among those who completed the PALISADE trial, the estimated reduction of accidental exposure related AR risk was 94.9% for AR101 and 6.4% for placebo. For AR101-treated subjects who achieved the primary endpoint of 600 mg MTD or higher, the associated AR risk reduction was 97.2%. The results were consistent across different parametric distribution assumptions.

CONCLUSIONS: OIT with AR101 resulted in a significantly higher reduction in AR risk related to accidental exposure compared to placebo. In contrast to previous analyses that used unintended allergen residue from packaged food as the peanut intake assumption, this approach more closely reflects the real-world dietary experience of patients practicing peanut avoidance and thus provides a more appropriate estimate of treatment benefit.