Regulatory Decision Summary for Dupixent

Chronic rhinosinusitis with nasal polyposis (CRSwNP) is a disease characterized by inflammation of the nose and paranasal sinuses, tissue edema, nasal obstruction, and increased mucus production causing symptoms including nasal congestion, loss of smell, and rhinorrhea that persists for at least 12 weeks. CRSwNP, particularly more severe variants, is associated with significant morbidity and decreased quality of life.

The benefits of Dupixent as an add-on maintenance treatment with intranasal corticosteroids in adult patients with severe CRSwNP inadequately controlled by systemic corticosteroids and/or sino-nasal surgery was established in the pivotal trials SINUS-24 and SINUS-52.

In SINUS-24 and SINUS-52, Dupixent resulted in a statistically significant reduction of bilateral endoscopic nasal polyp score (e.g., polyp size) and nasal congestion at Week 24 in subjects with CRSwNP. Additionally, statistically significant differences in favour of Dupixent were observed at Week 24 in the reduction of sinonasal inflammation/opacification , improved sense of smell and improved health-related quality of life with respect to nasal symptoms. Favourable changes in these endpoints at Week 52 were consistent with results observed at Week 24. Dupixent also resulted in the significant reduction of systemic corticosteroid use or need for sino-nasal surgery versus placebo.

In SINUS-24 and SINUS-52, the incidence of adverse events (AEs) was generally consistent when comparing Dupixent to placebo, with few serious AEs, AEs of special interest, and discontinuations due to AEs reported during the clinical trials. Treatment-emergent AEs were generally of mild-to-moderate intensity.

Serious AEs of eosinophilia, including vasculitis consistent with eosinophilic granulomatosis with polyangiitis, have been reported in subjects with CRSwNP and comorbid asthma receiving Dupixent; asthma is highly associated with CRSwNP. Identified risks are considered sufficiently mitigated by product labelling and routine pharmacovigilance activities.

There were few subjects 65 years of age and older enrolled in SINUS-24 and SINUS-52; however, no pronounced risks were identified in these subjects. While long-term safety data reflective of the intended chronic treatment remains limited, no additional risks were identified by Week 52 relative to Week 24.

Overall, based on the data and information evaluated as part of this assessment, the BRDD considers there to be a positive benefit-risk profile for Dupixent (dupilumab injection), which supports an extension to the indication as an add-on maintenance treatment with intranasal corticosteroids in adult patients with severe CRSwNP inadequately controlled by systemic corticosteroids and/or sino-nasal surgery.