About the MANDARA Clinical Trial
Trial Name: Efficacy and Safety of Benralizumab in EGPA Compared to Mepolizumab
ClinicalTrials.gov ID: NCT04157348
Sponsor: AstraZeneca
Completion Date (Estimated): March 2026
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Positive Results Show Benefits of Benralizumab for Eosinophilic Granulomatosis With Polyangiitis
The results were presented as a late-breaking poster presentation at the American Academy of Allergy, Asthma, and Immunology Annual Meeting.
The New England Journal of Medicine published positive results from the MANDARA (NCT04157348) phase 3 trial of benralizumab (Fasenra; AstraZeneca) for individuals with eosinophilic granulomatosis with polyangiitis (EGPA), following the late-breaking poster presentation at the American Academy of Allergy, Asthma, and Immunology Annual Meeting.1,2
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“Patients with EGPA typically rely on long-term, high dose [oral corticosteroids (OCS)], which can cause serious and lasting [adverse events], and often suffer recurrent relapses when attempting to taper off their treatment. These findings are an exciting step forward as they affirm that eosinophil-targeting biologic treatments helped more patients achieve remission and taper off of steroid therapy,” Michael Wechsler MD, MMSc, professor of Medicine and director of The Asthma Institute at National Jewish Health, said in a press release from the company.1
Investigators of the study compared benralizumab to mepolizumab (Nucala; GlaxoSmithKline) for individuals with EGPA who were receiving OCS with or without stable immunosuppressive therapy, according to the press release. Treatment was randomly assigned to patients as either a single 30 mg subcutaneous injection of benralizumab or 3 separate 100 mg subcutaneous injections of mepolizumab, once every 4 weeks.1
The results showed benralizumab met the primary endpoint of adjusted rate of remission and demonstrated non-inferior rates of remission compared to mepolizumab, according to the press release. The adjusted rate of remission for benralizumab was 59% at 36 and 48 weeks compared to 56% for mepolizumab, defined by the Birmingham Vasculitis Activity Score and OCS dose of less than or equal to 4 mg per day. Furthermore, 41% of patients were able to fully taper off of OCS during weeks 48 through 52 compared to 26%, respectively. Approximately 86% and 74%, respectively, had at least a 50% reduction in OCS dose during the same time period, according to the press release.1
Benralizumab was also associated with a greater reduction in blood eosinophil counts from week 1 at 0.15 compared to mepolizumab at 0.39, and the reduction was maintained through all time points. At week 52, the count was 0.10 compared with 0.26.1
There were no new safety signals identified and the drug was well tolerated, according to the press release. The most common adverse reactions included headache and pharyngitis, with injection site reactions occurring at a rate of 2.2% for those treated with benralizumab.1
“The results from this trial are an important step forward for the EGPA community, as this is the first trial to demonstrate that remission from EGPA with an eosinophil-targeting biologic is achievable for the majority of patients. This is a significant advancement and shows that benralizumab helped patients achieve remission and reduce chronic OCS usage, in a convenient, single, monthly subcutaneous injection, and could alleviate some of the impact of this debilitating disease,” Sharon Barr, executive vice president of BioPharmaceuticals Research and Development at AstraZeneca, said in the press release.1
Currently, benralizumab is approved as an add-on maintenance treatment for severe allergies in those aged 12 and older in the United States, and is approved for self-administration, according to the press release. The indication also includes those with an eosinophilic phenotype.1
References
MANDARA Phase III data published in New England Journal of Medicine show remission is an achievable goal in eosinophilic granulomatosis with polyangiitis (EGPA) with Fasenra. News release. AstraZeneca. February 23, 2024. Accessed February 26, 2024. https://www.astrazeneca-us.com/media/press-releases/2024/mandara-phase-iii-data-published-in-new-england-journal-of-medicine-show-remission-is-an-achievable-goal-in-eosinophilic-granulomatosis-with-polyangiitis-egpa-with-fasenra.html
Wechsler ME, Nair P, Terrier B, et al. Benralizumab versus Mepolizumab for Eosinophilic Granulomatosis with Polyangiitis. N Engl J Med. 2024. doi:10.1056/NEJMoa2311155
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