Long-Term Efficacy and Safety of Benralizumab Treatment for PDGFRA-Negative Hypereosinophilic Syndrome.

Background: Therapies for hypereosinophilic syndromes (HES) have variable efficacy and significant toxicity. Benralizumab (BENRA), an afucosylated monoclonal antibody that binds interleukin 5 receptor α expressed on eosinophils, reduced blood and tissue eosinophils in a 48-week, phase 2 study in PDGFRA-negative HES.

Objective: To assess safety and efficacy of long-term BENRA treatment in PDGFRA-negative HES.

Methods: Twenty PDGFRA-negative HES patients with severe and diverse clinical manifestations were treated in a double-blind, placebo-controlled clinical trial of BENRA (NCT02130882). Fourteen were followed on an open-label extension. Efficacy and safety were reviewed at each visit.

Results: Among 14 long-term participants, 3 withdrew owing to loss of efficacy, and 1 owing to death unrelated to drug after 2 to 6 years. The remaining 10 participants received BENRA for at least 8 years (maximum exposure 10.1 y). Peripheral eosinophil counts remained suppressed in all participants. Eight participants attempted to taper from monthly to every-2-month dosing, of which 5 resumed monthly dosing owing to increased symptoms and/or eosinophil count. There were 11 serious adverse events: 10 hospitalizations (3 for infections, 5 for surgeries, and 2 for drug desensitization or observation) and 1 death from antibiotic-associated toxic epidermal necrolysis. None were attributed to BENRA. Eight participants reported injection-site reactions (23 total), all mild in severity and self-limited. Three malignancies and no parasitic infections were reported. Despite sustained eosinophil depletion, immunoglobulin levels and peripheral T-, B-, and natural killer-cell counts were stable for the duration of the study.

Conclusions: Long-term BENRA therapy is effective and well-tolerated in HES patients without significant adverse effects.