EU approves Dupixent for chronic rhinosinusitis with nasal polyposis.- Sanofi

The European Commission approved a new indication for Dupixent (dupilumab), from Sanofi, in chronic rhinosinusitis with nasal polyposis (CRSwNP). Dupixent is indicated as an add-on therapy with intranasal corticosteroids for the treatment of adults with severe CRSwNP for whom therapy with systemic corticosteroids and/or surgery do not provide adequate disease control.

The EC approval is based on two pivotal Phase 3 trials (the 24-week SINUS-24 and 52-week SINUS-52) that evaluated Dupixent 300 mg every two weeks plus standard-of-care intranasal corticosteroids compared to placebo plus intranasal corticosteroids. In these trials, Dupixent significantly improved key disease measures and met all primary and secondary endpoints. At 24 weeks, patients treated with Dupixent achieved statistically significant improvements in all primary and secondary endpoints, including 57% and 51% improvement in their nasal congestion/obstruction severity compared to a 19% and 15% improvement with placebo in SINUS-24 and SINUS-52, respectively (least squares [LS] mean change from baseline of -1.34 and -1.25 for Dupixent compared to -0.45 and -0.38 for placebo; difference between Dupixent and placebo: -0.89 and -0.87). Also shown was a 33% and 27% reduction in their nasal polyps score compared to a 7% and 4% increase with placebo in SINUS-24 and SINUS-52, respectively (LS mean change from baseline of -1.89 and -1.71 for Dupixent compared to 0.17 and 0.10 for placebo; difference between Dupixent and placebo: -2.06 and -1.80). Secondary endpoints include a 42% and 27% improvement in sinus opacification compared to 4% and 0% with placebo in SINUS-24 and SINUS-52, respectively (LS mean change from baseline of -8.18 and -5.21 for Dupixent compared to -0.74 and -0.09 for placebo). There was a 52% and 45% improvement in loss of smell compared to a 12% and 10% improvement for placebo in SINUS-24 and SINUS-52, respectively (LS mean difference in Dupixent compared to placebo of -1.12 and -0.98 in SINUS-24 and SINUS-52, respectively). In a pre-specified pooled analysis of the two trials up to 52 weeks, Dupixent treatment resulted in a significant reduction of systemic corticosteroid use and the need for sino?nasal surgery compared to placebo.

Comment: Dupixent comes in a 300 mg pre-filled syringe for patients with CRSwNP. It is given as a subcutaneous injection every other week at different injection sites. Dupixent is intended for use under the guidance of a healthcare professional and can be given in a clinic or at home by self-administration after training by a healthcare professional. In addition to severe CRSwNP, Dupixent is approved in the EU for patients 12 years and older as an add-on maintenance treatment for severe asthma with type 2 inflammation characterized by raised blood eosinophils and/or raised fractional exhaled nitric oxide (FeNO), who are inadequately controlled with high dose inhaled corticosteroid (ICS) plus another medicinal product for maintenance treatment. It is also approved in the EU for use in patients 12 years and older with moderate-to-severe atopic dermatitis who are candidates for systemic therapy.