FDA Approves Benralizumab for Eosinophilic Granulomatosis with Polyangiitis

Benralizumab has received approval from the US Food and Drug Administration (FDA) for the treatment of adult patients with eosinophilic granulomatosis with polyangiitis (EGPA) based on data from the phase 3 MANDARA trial.

Announced by AstraZeneca on September 18, 2024, the approval comes less than 7 months after the pivotal MANDARA trial was published in the New England Journal of Medicine. The trial, which compared benralizumab to the only FDA-approved therapy for EGPA at the time, mepolizumab (Nucala), was billed by AstraZeneca as the first head-to-head non-inferiority trial of biologics in patients with EGPA.^1,2

“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,” said MANDARA investigator Michael Wechsler, MD, MMSc, professor of Medicine and director of The Asthma Institute at National Jewish Health.¹ “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.”

Launched in 2019, the topline results from the MANDARA trial captivated the medical community when they were announced by AstraZeneca in September 2023. The study was presented as a late-breaking trial at the American College of Rheumatology 2023 annual meeting and, in February 2024, was published in the New England Journal of Medicine.^1,2

A 52-week, multicenter, double-blind, randomized, active-controlled noninferiority trial, MANDARA enrolled 140 adult patients with relapsing or refractory EGPA from 50 sites in 9 countries. These patients were randomized them in a 1:1 ratio to receive benralizumab 30 mg or mepolizumab 300 mg subcutaneously every 4 weeks for 52 weeks. Of note, relapsing or refractory disease was defined as a history of relapsing or refractory disease despite therapy with oral glucocorticoids at a dose of 7.5 to 50.0 mg of prednisolone per day or equivalent, with or without stable immunosuppressive therapy.²

The achievement of remission at weeks 36 and 48 was the primary outcome of interest for the trial. Investigators established a prespecified noninferiority margin of -25 percentage points and defined remission as a BVAS score of 0 and an oral glucocorticoid steroid dose less than or equal to 4 mg per day.²

Results demonstrated the adjusted percentage of patients achieving remission at weeks 36 and 48 was 59% among the benralizumab arm and 56% among the mepolizumab arm (difference, 3 percentage points; 95% Confidence interval [CI], -13 to 18; P = .73 for superiority). Secondary analysis of the trial indicated the duration of remission and the time to first relapse were similar in both treatment groups.²

In the trial manuscript, investigators also called attention to apparent reductions in blood eosinophil count from baseline to week 52, with reductions from 306.0 (SD, 225.0) to 32.4 (SD, 40.8) μL observed among the benralizumab group and reductions from 384.9 (SD, 563.6) to 71.8 (SD, 54.4) in the mepolizumab group. In their approval announcement, AstraZeneca highlighted the safety and tolerability profile for benralizumab within the trial was consistent with the known profile of the medicine, which boasts a previous approval for add-on maintenance treatment of patients with severe asthma aged 6 years and older and with an eosinophilic phenotype.^1,2

“This disease has a devastating impact on patients and the quality of their life, and they need more treatment options. The approval of another treatment in EGPA is welcome news to the approximately 15,000 patients living in the US with this difficult-to-treat rare disease,” said Joyce Kullman, executive director of the Vasculitis Foundation.¹

References:

1. ^{AstraZeneca. FASENRA approved in the US for eosinophilic granulomatosis with polyangiitis. AstraZeneca. September 18, 2024. Accessed September 18, 2024. https://www.astrazeneca.com/media-centre/press-releases/2024/fasenra-approved-in-the-us-for-eosinophilic-granulomatosis-with-polyangiitis.html.}
2. ^{Campbell P. Mandara: Benralizumab proves noninferiority to mepolizumab for EGPA. HCP Live. February 23, 2024. Accessed September 18, 2024. https://www.hcplive.com/view/mandara-benralizumab-proves-noninferiority-to-mepolizumab-for-egpa.}