Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN) and Sanofi today announced that the European Commission (EC) has approved a new indication for Dupixent® (dupilumab) 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.

"People living with severe CRSwNP are often desperate to find new treatment options, given that current standard treatments such as intermittent courses of systemic corticosteroids or sinonasal surgery are associated with disease recurrence," said George D. Yancopoulos, M.D., Ph.D., President and Chief Scientific Officer at Regeneron. "Dupixent significantly improved the signs and symptoms of severe CRSwNP, and also eliminated the need for further surgery or corticosteroid use in approximately three-quarters of patients. Today's approval provides patients in Europe with the first biologic treatment to address the type 2 inflammation that underlies most CRSwNP. This is the third type 2 disease in which Dupixent has been approved, and we continue to investigate Dupixent in a broad range of type 2 inflammatory diseases."

CRSwNP is a chronic disease of the upper airway that obstructs the sinuses and nasal passages. It can lead to persistent breathing difficulties, nasal congestion and discharge, reduced or loss of sense of smell and taste, and facial pressure or pain.

"Many patients with CRSwNP have co-morbid asthma, and those patients tend to have more severe disease that is often more difficult to treat," said John Reed, M.D., Ph.D., Global Head of Research and Development at Sanofi. "These particular patients may have an increased risk of asthma attacks, high symptom burden and a substantial adverse impact on health-related quality of life. Nearly 60 percent of the patients in the CRSwNP trials had asthma, and the data showed Dupixent provided an additional benefit of improved lung function in these patients."

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:

• Co-primary endpoints:
  • 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).
  • 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:
  • 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).
  • 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.

• The proportion of patients who required systemic corticosteroids was reduced by 74% with Dupixent compared to placebo.
• The proportion of patients who required surgery was reduced by 83% with Dupixent compared to placebo.

In a pre-specified analysis of the 59% of patients who also had asthma, treatment with Dupixent:

• Improved lung function by 0.21 L compared with placebo as measured by forced expiratory volume over one second (FEV1).
• Improved asthma control as measured by the 6-item Asthma Control Questionnaire (ACQ-6).

Treatment effects on nasal congestion and loss of smell were observed with the first assessment at 4 weeks and showed continued improvement for the duration of the trials.

In the CRSwNP clinical trials, the common (at least 1%) adverse events in the Dupixent group were inflammation of the eye and eyelids (conjunctivitis), high count of certain white blood cells (eosinophilia), injection site reactions and injection site swelling.

Dupixent is a fully-human monoclonal antibody that inhibits the signaling of the interleukin-4 (IL-4) and interleukin-13 (IL-13) proteins. Dupixent was invented using Regeneron's proprietary VelocImmune® technology, which uses a unique genetically-humanized mouse to produce optimized fully-human antibodies. Data from Dupixent clinical trials have shown that IL-4 and IL-13 are key drivers of the type 2 inflammation that plays a major role in CRSwNP, asthma and atopic dermatitis.