Fasenra met the primary endpoint in the MANDARA phase III trial in eosinophilic granulomatosis with polyangiitis (EGPA)

MANDARA is the first Phase III head-to-head trial of biologics in EGPA and compared the efficacy and safety of Fasenra versus mepolizumab, the only currently approved treatment. In the blinded trial, patients were randomised to receive either a single 30mg subcutaneous injection of Fasenra or three separate 100mg subcutaneous injections of mepolizumab once every four weeks.

EGPA is a rare, immune-mediated vasculitis that is caused by inflammation of small to medium-sized blood vessels Approximately half of patients with EGPA have concomitant adult-onset severe eosinophilic asthma (SEA). EGPA can result in damage to multiple organs, including lungs, skin, heart, gastrointestinal tract and nerves, which accumulates over time and without treatment can be fatal.

Dr Michael Wechsler, Principal Investigator said: “The positive MANDARA trial results are exciting because patients with eosinophilic granulomatosis with polyangiitis have limited treatment options but face crippling symptoms, which can even be fatal if not treated. This trial demonstrates that a biologic medicine given in a single monthly injection could help patients achieve remission rates comparable to the current standard of care, adding to the importance of benralizumab as a potential treatment option for eosinophilic granulomatosis with polyangiitis.”

MANDARA: MANDARA was a randomised, double blind, double-dummy, active-controlled, parallel group, multicentre 52-week Phase III trial which compared the efficacy and safety of Fasenra to mepolizumab in adult patients with relapsing or refractory EGPA. In the blinded trial, 140 patients were randomised 1:1 (70 per treatment group) to receive either a single 30mg subcutaneous injection of Fasenra or three separate 100mg subcutaneous injections of mepolizumab once 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 4mg/day. Fasenra remission was compared to the historical placebo rate from mepolizumab’s Phase III trial, MIRRA. The primary statistical analysis was to demonstrate non-inferiority of Fasenra versus mepolizumab based on the primary endpoint. All patients who complete the 52-week double-blind treatment period may be eligible to continue into an open label extension (OLE) period, intended to allow each patient at least one year of treatment with open-label Fasenra.