Regulatory Decision Summary for Nucala

Hypereosinophilic syndrome (HES) is a group of rare disorders marked by the sustained overproduction of eosinophils, in which eosinophilic infiltration and mediator release cause damage to multiple organs. The overall goals of therapy are reduction of in eosinophil count, amelioration of signs and symptoms, and prevention of disease progression. Patients with myeloid variants (eg, FIP1L1-PDGFRα [F/P]-positive HES) are treated initially with imatinib, while those with other types of HES are treated with an initial trial of corticosteroids. Clinical responses to these therapies, however, are incomplete or inadequate in over 80% of HES patients (among those negative for F/P mutation). Inadequate HES treatment can lead to profound end-organ damage and increased mortality.

In a single pivotal trial, in subjects with a history of relapsing or refractory HES on stable oral corticosteroid therapy with or without cytotoxic or immunosuppressive HES therapy, Nucala (mepolizumab for injection, 300 mg subcutaneously once every 4 weeks) as an add-on to standard of care resulted in a 50% reduction in the proportion of subjects who experienced HES flare (or withdrew) during the 32-week treatment period relative to placebo. Other measures of efficacy, including the rate of HES flare, time to first HES flare, and fatigue level favoured Nucala therapy relative to placebo.

The safety data from the single pivotal trial, as well as supportive safety data three other trials and from the HES expanded access programme, did not indicate that there were any new safety signals associated with Nucala treatment that had not been previously identified in clinical trials for other indications.

Overall, based on the data evaluated as part of this submission, the Biologic and Radiopharmaceutical Drugs Directorate (BRDD) considers there to be sufficient evidence at this time to conclude that the benefit-risk profile for Nucala as an add-on to standard therapy for the treatment of adult patients with hypereosinophilic syndrome (HES) for ≥6 months without an identifiable non-hematologic secondary cause is considered favourable.