FDA Approves Benralizumab for Eosinophilic Granulomatosis With Polyangiitis

The FDA has approved an expanded indication of AstraZeneca’s benralizumab (Fasenra) in the US for the treatment of adult patients with eosinophilic granulomatosis with polyangiitis (EGPA), a rare, immune-mediated vasculitis that can result in damage to multiple organs and can be fatal without treatment.¹

The FDA approved benralizumab (Fasenra) for adult patients with eosinophilic granulomatosis with polyangiitis (EGPA). | Imaged credit: ra2studio -stock.adobe.com

The approval was based on positive results from the MANDARA phase 3 trial (NCT04157348), which evaluated the efficacy and safety of benralizumab compared with the only approved EGPA treatment, mepolizumab, in patients with relapsing or refractory EGPA.

“This approval is great news for patients with EGPA in the US who continue to suffer from debilitating symptoms,” said Michael Wechsler, MD, MMSc, professor of medicine and director of The Asthma Institute at National Jewish Health, and international coordinating investigator of the MANDARA trial, in a statement.¹ “Patients often rely on long-term oral corticosteroids, which can cause serious and lasting side effects. 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.”

The study was a multicenter, double-blind, phase 3, randomized, active-controlled noninferiority trial, in which adults with relapsing or refractory EGPA who were receiving standard care were randomly assigned 1:1 to receive benralizumab (30 mg) or mepolizumab (300 mg) subcutaneously every 4 weeks for 52 weeks.²

The primary end point was remission at weeks 36 and 48, while secondary end points included the accrued duration of remission, time to first relapse, oral glucocorticoid use, eosinophil count, and safety.

A total of 140 patients were included in the study. The adjusted percentage of patients with remission at weeks 36 and 48 was 59% in the benralizumab group and 56% in the mepolizumab group (difference, 3 percentage points; 95% CI, –13 to 18; P = 0.73), showing noninferiority but not superiority of benralizumab to mepolizumab.

Additionally, 41% of patients treated with benralizumab fully tapered off oral corticosteroids compared with 26% of patients in the mepolizumab arm (difference, 16 percentage points; 95% CI, 1-31).

Furthermore, adverse events were reported in 90% of patients who received benralizumab and in 96% of patients who received mepolizumab. Serious adverse events were reported in 6% of patients in the benralizumab group and in 13% of patients in the mepolizumab group, respectively.

Benralizumab is indicated as an add-on maintenance treatment for adult and pediatric patients 6 years and older with severe asthma, and with an eosinophilic phenotype. It is now also indicated for the treatment of adult patients with EGPA.³

The recommended dose of benralizumab for patients with EGPA is 30 mg administered every 4 weeks by subcutaneous injection.

“Fasenra is already well established for the treatment of severe eosinophilic asthma, and with this approval, physicians in the US will now be able to offer an important new, convenient single monthly subcutaneous injection to their patients with EGPA,” said Ruud Dobber, executive vice president, BioPharmaceuticals Business Unit, AstraZeneca, in a statement.¹ “Today’s news demonstrates the potential of Fasenra to help patients suffering from eosinophilic diseases beyond severe asthma.”

References

1. Fasenra approved in the US for eosinophilic granulomatosis with polyangiitis. News release. AstraZeneca. Published September 18, 2024. Accessed September 18, 2024. https://www.astrazeneca-us.com/media/press-releases/2024/fasenra-approved-in-the-us-for-eosinophilic-granulomatosis-with-polyangiitis.html

2. Wechsler ME, Nair P, Terrier B, et al. Benralizumab versus mepolizumab for eosinophilic granulomatosis with polyangiitis. N Engl J Med. 2024;390(10):911-921. doi:10.1056/nejmoa2311155

3. Fasenra. Package insert. AstraZeneca; 2024. Accessed September 18, 2024. https://den8dhaj6zs0e.cloudfront.net/50fd68b9-106b-4550-b5d0-12b045f8b184/3647bed4-ce91-4fe7-9bc5-32dbee73f80a/3647bed4-ce91-4fe7-9bc5-32dbee73f80a_viewable_rendition__v.pdf