Fasenra (benralizumab) approved in the US for eosinophilic granulomatosis with polyangiitis

EGPA is a rare, immune-mediated vasculitis that can result in damage to multiple organs, and without treatment, can be fatal. 

The approval by the FDA was based on positive results from the MANDARA Phase III trial published in The New England Journal of Medicine (previously cited)  which compared the efficacy and safety of Fasenra to the only approved EGPA treatment, mepolizumab, in patients with relapsing or refractory EGPA. MANDARA was the first head-to-head non-inferiority trial of biologics in patients with EGPA. Patients were randomised to receive either a single 30 mg subcutaneous injection of Fasenra or three separate 100 mg subcutaneous injections of mepolizumab every four weeks. In the trial, nearly 60% of Fasenra-treated patients achieved remission which was comparable to mepolizumab-treated patients. Data also showed 41% of Fasenra -treated patients fully tapered off oral corticosteroids (OCS) (vs. 26% in the mepolizumab arm (difference: 16%; 95% CI: 1,31)).

Dr. Michael Wechsler, Professor of Medicine and Director of The Asthma Institute at National Jewish Health, and International Coordinating Investigator of the MANDARA trial said: “This approval is great news for patients with EGPA in the US who continue to suffer from debilitating symptoms. Patients often rely on long-term oral corticosteroids, which can cause serious and lasting side effects. Benralizumab is a much-needed treatment option, with data showing that not only is remission an achievable goal for EGPA patients, but benralizumab can also help patients taper off steroid therapy.”

MANDARA; MANDARA was a Phase III, randomised, double-blinded, active-controlled trial, which compared the efficacy and safety of Fasenra  to mepolizumab in adult patients with relapsing or refractory EGPA.5 In the trial, 140 patients were randomised 1:1 to receive either a single 30mg subcutaneous injection of Fasenra  or three separate 100mg subcutaneous injections of the active comparator every four weeks. The primary endpoint was the proportion of patients who were in remission at both weeks 36 and 48.  Remission is defined as Birmingham Vasculitis Activity Score (BVAS)=0 and OCS dose less than or equal to 4 mg/day.  A secondary endpoint was the proportion of patients who were able to fully taper off OCS at weeks 48 through 52.  The primary statistical analysis was to demonstrate non-inferiority of Fasenra versus mepolizumab based on the primary endpoint.