Positive high-level results from the MANDARA Phase III trial showed AstraZeneca’s Fasenra (benralizumab) met the primary endpoint of the trial and demonstrated non-inferior rates of remission compared to mepolizumab in patients with eosinophilic granulomatosis with polyangiitis (EGPA) who were receiving oral corticosteroids (OCS) with or without stable immunosuppressive therapy.
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).
The positive MANDARA trial results are exciting because patients with eosinophilic granulomatosis with polyangiitis today have limited treatment options
- Dr Michael Wechsler, Principal Investigator
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 today have limited treatment options but face crippling symptoms, which can even be fatal if not treated.”
Wechsler continued: “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.”
Sharon Barr, Executive VP of BioPharmaceuticals at R&D, AstraZeneca, said: “The positive results from MANDARA demonstrate that Fasenra, which has a unique mechanism of action and directly targets eosinophils, can help patients achieve remission from the debilitating impacts of this inflammatory disease with a more convenient single monthly subcutaneous injection.”
The safety and tolerability profile for Fasenra in the trial was consistent with the known profile of the medicine.
Full results from MANDARA will be presented at an upcoming medical meeting and data will be shared with health authorities around the world.
Fasenra is a monoclonal antibody that binds directly to IL-5 receptor alpha on eosinophils and attracts natural killer cells to induce rapid and near-complete depletion of blood and tissue eosinophils in most patients via apoptosis (programmed cell death).
Fasenra is currently approved as an add-on maintenance treatment for SEA in the US, EU, Japan and other countries, and is approved for self-administration in the US, EU and other countries.
The FDA granted Orphan Drug Designation for Fasenra for EGPA in 2018 and AstraZeneca continues to explore Fasenra’s potential beyond severe asthma, as a treatment across many diseases where eosinophils are expected to play a role.
