Benralizumab emerges as a promising therapy for eosinophilic granulomatosis with polyangiitis (EGPA), according to a group of Canadian investigators. They reported that benralizumab offers a hopeful alternative to mepolizumab and holds potential for the treatment of EGPA. The study’s findings were published in the New England Journal of Medicine.
EGPA, also known as Churg-Strauss Syndrome, is characterized by inflammation in small to medium-sized blood vessels, resulting in elevated blood and tissue eosinophil counts. This immune response can lead to damage in vital organs such as the lungs, skin, heart, gastrointestinal tract, and nerves, with respiratory complications being one of the most common symptoms associated with this syndrome.
The multicenter, double-blind, phase 3, randomized, active-controlled noninferiority trial was conducted by Wechsler and colleagues to evaluate the effectiveness of benralizumab compared to mepolizumab. The trial involved adult participants with relapsing or refractory EGPA who were receiving standard care. The participants were randomly assigned to receive either benralizumab (30 mg) or mepolizumab (300 mg) through monthly subcutaneous injections for 52 weeks. The primary endpoint of the trial was remission at weeks 36 and 48. The secondary endpoints included the duration of remission, time to relapse, oral glucocorticoid use, eosinophil count, and safety.
The study has revealed that benralizumab is equally effective as mepolizumab in reducing exacerbations and inducing disease remission over 52 weeks. Additionally, administering a single 30 mg subcutaneous dose of benralizumab is more advantageous than using three 100 mg subcutaneous doses of mepolizumab, thus providing a more streamlined approach for patients undergoing treatment. In addition, the study has also shown that approximately 16 percent more patients in the benralizumab group were able to avoid using oral corticosteroids as compared to the mepolizumab group. This is a significant finding since patients with EGPA often depend on oral corticosteroids such as prednisone to manage their symptoms, despite the associated adverse effects. The researchers have emphasized that although prolonged use of prednisone reduces the risk of relapse of EGPA symptoms, it also comes with progressive toxic effects.
Both benralizumab and mepolizumab, categorized as biologic drugs derived from living organisms or their cells through biotechnology, targeted eosinophils. By inhibiting signals or receptors drawing eosinophils into tissues, such as the lungs, both drugs effectively curtailed eosinophil concentrations, thereby alleviating symptoms.
Wechsler and colleagues noted that benralizumab exhibited greater blood eosinophil depletion compared to mepolizumab, starting from week one onwards. Encouragingly, both drugs demonstrated excellent tolerance throughout the trial, with no new adverse events reported. Importantly, benralizumab proved non-inferior to mepolizumab for inducing remission in patients grappling with relapsing or refractory EGPA.
Given the progressive toxic effects of prolonged corticosteroid use, this finding underscores the potential of benralizumab to improve the management of EGPA while minimizing the dependance on corticosteroids. Both benralizumab and mepolizumab, as biologic drugs targeting eosinophils, have shown promising results in reducing eosinophil concentrations and alleviating EGPA symptoms. The study findings hold promise for improving outcomes and quality of life for individuals affected by this challenging condition.
Reference
Wechsler ME, Nair P, Terrier B, Walz B, Bourdin A, Jayne DRW, et al. Benralizumab versus Mepolizumab for Eosinophilic Granulomatosis with Polyangiitis. New England Journal of Medicine. 2024 Feb 23;0(0).