FASENRA Achieves Remission in EGPA, According to NEJM-Published MANDARA Trial

Recent findings from the MANDARA Phase III trial have highlighted the potential of FASENRA® (benralizumab) in aiding patients with Eosinophilic Granulomatosis with Polyangiitis (EGPA) to reduce their reliance on oral corticosteroids (OCS) while effectively managing the disease. Published in the New England Journal of Medicine, the trial results demonstrated that over half of the patients treated with benralizumab achieved remission, a significant advancement in the treatment of EGPA.

The MANDARA trial was a comparative study that pitted benralizumab against mepolizumab in EGPA patients who were on OCS, with or without stable immunosuppressive therapy. The trial showed that benralizumab not only met its primary endpoint but also exhibited non-inferior rates of remission when compared to mepolizumab. A noteworthy 59% of benralizumab-treated patients were in remission at weeks 36 and 48, closely followed by 56% of mepolizumab-treated patients.

Furthermore, a substantial number of patients treated with FASENRA were able to completely discontinue OCS during weeks 48 through 52, with 41% in the benralizumab group versus 26% in the comparator group. Additionally, 86% of benralizumab patients had at least a 50% reduction in OCS dose during the same period.

Dr. Michael Wechsler, a key opinion leader in the field and the International Coordinating Investigator of the MANDARA trial, emphasized the importance of these findings. He noted that EGPA patients typically depend on long-term, high-dose OCS, which can lead to severe side effects and frequent relapses when attempting to reduce the treatment. The results from the trial indicate that eosinophil-targeting biologic treatments, such as benralizumab, can help more patients achieve remission and reduce their dependence on steroid therapy.

Sharon Barr, Executive Vice President of BioPharmaceuticals R&D at AstraZeneca, highlighted the significance of these results for the EGPA community. She stated that this is the first trial to show that remission from EGPA with an eosinophil-targeting biologic is attainable for the majority of patients, marking a significant step forward in treating this debilitating disease.

The unique mode of action of FASENRA, which leads to the near-complete depletion of eosinophils, was also noted in the trial. Benralizumab was associated with a greater reduction in blood eosinophil counts from week 1 compared to mepolizumab and maintained this reduction throughout the study. The safety profile of benralizumab was found to be consistent with the known profile of the medicine, with no new safety signals.

Currently, FASENRA is approved as an add-on maintenance treatment for severe eosinophilic asthma in over 80 countries, including the US, Japan, and the EU, and is approved for self-administration in the US, EU, and other countries. AstraZeneca is actively engaging with regulatory authorities globally to make benralizumab available to EGPA patients as soon as possible.

The study underscores the role of elevated eosinophil levels in the pathophysiology of EGPA, a condition where patients often experience severe asthma, sinus, and nasal symptoms. The findings from the MANDARA trial offer hope for a more effective management of EGPA, potentially reducing the need for high-dose OCS and improving the quality of life for patients.