Regulatory Decision Summary for Fasenra and Fasenra Pen

This Supplement to a New Drug Submission (SNDS)-Clinical for Fasenra and Fasenra Pen was filed to propose a new indication for the treatment of eosinophilic granulomatosis with polyangiitis (EGPA; supported by the pivotal Phase 3 MANDARA study), to update long-term safety data (supported by the Open-Label safety extension MELTEMI study), to modify text related to self-administration in 4.1 Dosing Considerations, and to convert the Fasenra Product Monograph (PM) to the 2020 Master Template.

Fasenra and Fasenra Pen (benralizumab) is currently approved as an add-on maintenance treatment for adult patients with severe eosinophilic asthma. In this SNDS-Clinical, the sponsor proposed a new indication for the treatment of eosinophilic granulomatosis with polyangiitis (EGPA). To support the evaluation of efficacy and safety of benralizumab for this condition, the sponsor provided a single pivotal study (MANDARA).

MANDARA was a Phase 3, randomized, double-blind, active-controlled, multicenter, 52-week study with an open-label extension that evaluated the efficacy and safety of benralizumab (Fasenra) compared to mepolizumab in patients with EGPA. Patients also received standard of care therapy (a tapering course of oral corticosteroids [OCS]) throughout the study and may also have been receiving permitted concomitant immunosuppressive therapy. Eligible patients were males and females aged 18 or over, with relapsing or refractory, but not organ- or life-threatening, EGPA. A total of 140 patients (70 each in benralizumab and mepolizumab groups) were randomized. Demographic and baseline characteristics were balanced between the two groups.

The primary efficacy endpoint was the proportion of patients who achieved remission, which was defined as a Birmingham Vasculitis Activity Score (BVAS) of 0 and a daily OCS dose ≤ 4 mg/day, at Weeks 36 and 48. The non-inferiority (NI) margin of -25% that the sponsor selected was accepted by the clinical reviewer following consultation with the Office of Biostatistics within the Biologic and Radiopharmaceutical Drugs Directorate (BRDD). The adjusted remission rate was 57.7% in the benralizumab group and 56.5% in the mepolizumab group. Thus, the difference in remission rates was 1.21% (95% CI -14.11, 16.53), and as the lower bound of the 95% CI for the difference was greater than the NI margin, benralizumab was NI to mepolizumab. 

The safety profile of benralizumab in EGPA patients, based on the pivotal study MANDARA, was consistent with the known safety profile of benralizumab in eosinophilic asthma.

Overall, the benefit-risk profile was favourable for Fasenra 30 mg as an add-on treatment for adult patients with relapsing or refractory EGPA, when used under the conditions of use recommended in the approved Product Monograph. Therefore, a Notice of Compliance (NOC) was recommended.

Following Health Canada’s Marketed Health Product Directorate’s (MHPD’s) assessment of the submitted European Union-Risk Management Plan (EU-RMP), version 9.0 (dated 06 November 2023) and the RMP Canadian Specific Addendum (CSA), version 5 succession number 1 (dated 09 February 2024), it was concluded that the safety specifications and risk minimization plan provided in support of Fasenra (benralizumab) SNDS, is considered sufficient and acceptable.

The labelling information submitted met all applicable guidance and regulations.

For further details about Fasenra and Fasenra Pen, please refer to the Product Monograph, approved by Health Canada and available through the Drug Product Database.