D2.309 - HAL-MPE1, a novel subcutaneous immunotherapy candidate for peanut allergy. Phase I randomized placebo-controlled study

Following withdrawal of Palforzia, patients with peanut allergy lack disease-modifying treatment options. HAL developed HAL-MPE1, a subcutaneous immunotherapy (SCIT) candidate generally designed to induce desensitization in peanut allergic patients. The aim in this current, multi-centre, randomized, double-blind, placebo-controlled Phase I study was to assess the safety and peanut-specific IgG4 induction in peanut-allergic patients undergoing treatment with HAL- MPE1/placebo.

Fourty-two peanut-allergic subjects were enrolled in a staggered design: adults (HAL n=8/placebo n=4), adolescents (n=10/5), and children (n=9/6). Inclusion required prior systemic reaction, peanut-specific IgE >5 kU/L, Ara h 2-specific IgE >2 kU/L, and positive skin prick test. Thirteen weekly up-dosing injections (0.05–375 µg peanut protein) were followed by two 375 µg maintenance doses at 1- and 2-week intervals; up to five additional injections were permitted. Total duration was 16–21 weeks. Safety and peanut-specific IgG4 were assessed.

Eighty-five percent of HAL-MPE1 recipients reached 375 µg. No grade III/IV systemic reactions occurred. In the pooled HAL group (n=27), systemic reactions occurred in 48% (grade I: 19%; grade II: 30%) vs 27% in the placebo group (N=15). Local reactions (all mild to moderate) occurred in 63% in the active group vs 47% in the placebo group. Three SAEs have been reported within the active group: One grade II reaction at 37.5 µg, one eosinophilic esophagitis, and one grade II asthma exacerbation. After three maintenance doses, marked increases in peanut-specific IgG4 were observed. Geometric mean fold increases (GMFI) were 3.39 for total peanut IgG4 and 4.45 (Ara h 1), 3.44 (Ara h 2), 9.08 (Ara h 3), and 1.72 (Ara h 6). Specific- IgG4 increase was most pronounced in the cohort of children: In children (median age 9 years), total IgG4 GMFI reached 5.19 at study end (p<0.0001). 

HAL-MPE1 demonstrated acceptable tolerability across all age groups and robust induction of peanut-specific IgG4 within 16–21 weeks treatment, supporting further clinical development of SCIT for peanut allergy.