Regulatory Decision Summary for Nucala

There is currently no therapy specifically indicated for the treatment of patients with EGPA that is approved in Canada. Systemic glucocorticoids (e.g., prednisone or equivalent) are the cornerstone of treatment for EGPA; however, risks associated with chronic use of corticosteroids are well established.

In subjects with a history of relapsing or refractory EGPA on stable oral corticosteroid therapy with or without concomitant stable immunosuppressant therapy, Nucala (mepolizumab for injection, 300 mg subcutaneously once every 4 weeks) as an add-on to corticosteroids resulted in a statistically significant greater accrued time in remission compared with placebo (odds ratio: 5.9 [95% CI: 2.7, 13.0]; p<0.001). Nucala additionally resulted in a significantly larger proportion of subjects in remission during the latter weeks of the study compared with placebo (odds ratio: 16.7 [95% CI: 3.6, 77.7]; p<0.001), indicating a durability of treatment response. The benefit of Nucala on the induction/maintenance of remission was further demonstrated by a significantly longer duration of uninterrupted sustained remission, and a statistically significant longer time to first relapse compared with placebo.

Treatment with Nucala additionally resulted in a statistically significant greater reduction in oral corticosteroid dose compared to placebo, and a greater proportion of subjects achieving a clinically meaningful reduction in oral corticosteroid dose during the latter weeks of the study compared to placebo, further demonstrating a durability of treatment response. The benefit in some subgroups, including subjects receiving >20mg/day of oral corticosteroids, is uncertain.

The incidence of on-treatment adverse events was similar when comparing Nucala to placebo, and adverse events considered to be serious were reported less frequently by patients receiving Nucala.

The occurrence of systemic allergic/hypersensitivity and non-allergic reactions were higher in patients receiving Nucala compared to those receiving placebo, although the overall incidence rate was considered low. These reactions are currently considered identified risks of treatment with Nucala. The safety profile of Nucala in the EGPA patient population does not indicate any potential risks beyond those previously identified for Nucala.

EGPA is a rare disease, and as such, clinical trial enrolment numbers are low, resulting in a degree of uncertainty related to treatment of the broader EGPA patient population with Nucala. Additionally, long-term safety data for a Nucala dose of 300 mg SC for the treatment of patients with EGPA is limited.

Overall, based on the data evaluated as part of this submission, the BGTD considers there to be sufficient evidence at this time to conclude that the benefit-risk profile for Nucala as an add-on to corticosteroids for the treatment of adult patients with eosinophilic granulomatosis with polyangiitis (EGPA) is considered favourable.