Benralizumab offers durability in EGPA, adds value to patients switched from mepolizumab

The attainment of remission in eosinophilic granulomatosis with polyangiitis (EGPA) is durable whether treated with benralizumab for 2 years or switched to benralizumab after 52 weeks of mepolizumab treatment, with additional merits observed among those who switched, as indicated in the open-label extension (OLE) of the MANDARA trial.

Of the patients randomized to benralizumab during the double-blind (DB) period who continued treatment in the OLE, 57.6 percent achieved remission at both weeks 36 and 48, followed by a remission rate of 62.1 percent at week 104. For those randomized to mepolizumab during the DB period who switched to benralizumab in the OLE, 61.3 percent were in remission at both weeks 36 and 48, while 67.7 percent were so at week 104. [AAAAI/WAO 2025, poster L07]

While the DB period of MANDARA showed that benralizumab led to more patients achieving complete oral glucocorticoid (OGC) withdrawal, those who switched from mepolizumab to benralizumab in the OLE were able to do so in a steadily increasing proportion over 52 weeks (25.8 percent during weeks 49–52 vs 43.5 percent during weeks 101–104). For the group receiving benralizumab for 2 years, the rates at the two timepoints remained similar (40.9 percent vs 43.9 percent).

The eosinophil-depleting effect was more pronounced with benralizumab, as evidenced by an additional, sustained drop in blood eosinophil (bEOS) count starting from 4 weeks after the switch from mepolizumab to benralizumab (from a median of 70 cells/μL at week 52 to 20 cells/μL at week 56).

“Discontinuation of OGCs was durable in patients receiving benralizumab, and in patients switching from mepolizumab to benralizumab, additional OGC sparing and bEOS depletion were seen,” said Professor Michael Wechsler from the National Jewish Health, Denver, Colorado, US. “These results provide evidence of the efficacy of 2 years of benralizumab treatment and of switching treatment from mepolizumab to benralizumab in patients with EGPA.”

First year of ongoing OLE

MANDARA was a phase III, randomized noninferiority trial assessing the efficacy and safety of benralizumab vs mepolizumab in the treatment of EGPA. All randomized patients were adults with relapsing or refractory disease despite OGC treatment, with or without immunosuppressive therapy. [N Engl J Med 2024;390:911-921]

The 52-week DB, head-to-head comparison served as the basis for the FDA's granting of a new indication for benralizumab for EGPA in adults in September 2024, followed by a similar extension of indication authorized by the EMA a month later.

Out of the 140 patients who underwent randomization, 128 (91.4 percent) entered the ongoing OLE, either continuing or switching to benralizumab in an open-label manner (mean age 52.8 years, 60.2 percent female, mean time since EGPA diagnosis 5.28 years). [ATS 2024, poster P630]

Remission was defined as Birmingham Vasculitis Activity Score (BVAS) of zero and OGC dose ≤4 mg prednisolone per day or equivalent.

Sustained remission and no relapses

For patients who achieved remission at week 24 of the DB period, the proportions of those who remained in remission until week 104 ('sustained remission') were 48.3 percent for continued benralizumab recipients and 55.2 percent for switchers from mepolizumab to benralizumab.

While OGCs could be tapered whenever a patient's BVAS was zero from week 4 onwards, the majority of patients receiving benralizumab in the OLE had no relapses during the period (77.3 percent with 2-year benralizumab and 67.7 percent with mepolizumab-to-benralizumab switch).

“In patients with EGPA receiving benralizumab, remission rates and bEOS depletion were durable over 2 years, with low relapse rates despite the tapering of OGCs and immunosuppressants,” concluded Wechsler.