Dupixent Demonstrates Success in Two Phase 3 Trials for Severe Chronic Rhinosinusitis with Nasal Polyps

February 27, 2019/BioValleyBIOON/-- French pharmaceutical giant Sanofi and its partner Regeneron recently at the 2019 American Academy of Allergy, Asthma & Immunology meeting held in San Francisco, USA,AsthmaandImmunologyDetailed data from two pivotal placebo-controlled Phase 3 clinical studies (SINUS-24 and SINUS-52) of the novel anti-inflammatory drug Dupixent (dupilumab) for the treatment of severe chronic rhinosinusitis with nasal polyps (CRSwNP) were presented at the American Academy of Allergy, Asthma & Immunology (AAAAI) Annual Meeting.

These two studies were conducted in adult patients with recurrent severe CRSwNP who had previously undergone surgery and/or systemic corticosteroid treatment but had inadequate disease control. The results showed that the studies met all primary and secondary endpoints: when added to standard-of-care intranasal corticosteroid spray, Dupixent improved nasal polyp size, severity of nasal congestion, chronic rhinosinusitis, olfaction, and comorbidities compared with placebo.AsthmaPrognosis. In these severe patients, Dupixent also reduced the need for systemic corticosteroids and nasal/sinus surgery.

Specific data were as follows: At the 24-week co-primary endpoints in two studies, patients receiving Dupixent plus standard of care with intranasal corticosteroid sprays showed improvements of 51% and 57%, respectively, in the severity of nasal congestion/obstruction, whereas those receiving placebo plus standard of care with intranasal corticosteroid sprays showed improvements of 15% and 19%, respectively (on a 0–3 scale, the Dupixent groups had reductions of 1.25 and 1.34 points, respectively, while the placebo groups had reductions of 0.38 and 0.45 points, respectively). Meanwhile, nasal polyp scores in the Dupixent groups decreased by 27% and 33%, respectively, whereas those in the placebo groups increased by 4% and 7%, respectively (polyp size assessed by endoscopy on a 0–8 scale: the Dupixent groups had reductions of 1.71 and 1.89 points, respectively, while the placebo groups had increases of 0.10 and 0.17 points, respectively).

Furthermore, in two studies, Dupixent also met all secondary endpoints, including: a significant reduction in the need for systemic corticosteroids or surgery, improvement in olfaction and chronic rhinosinusitis symptoms, and in a prespecified subgroup of patients with comorbid asthma, Dupixent also significantly improved lung function andAsthmaControl (p < 0.0001 for all primary and secondary endpoints in both studies).

In terms of safety, between the Dupixent treatment group and the placebo group in two studiesAdverse ReactionsThe incidence rates were generally similar, and no new or unexpected adverse events related to Dupixent were observed. Incidence of conjunctivitis: In the SINUS-24 study, 1.4% in the Dupixent group versus 0.8% in the placebo group; in the SINUS-52 study, 2.7% in the every-2-week Dupixent group, 2.0% in the every-2/4-week Dupixent group, and 1.3% in the placebo group. The overall incidence of serious adverse events was lower in the Dupixent treatment groups: In the SINUS-24 study, 4.2% in the Dupixent group versus 14.4% in the placebo group; in the SINUS-52 study, 5.4% in the every-2-week Dupixent group, 6.8% in the every-2/4-week Dupixent group, and 10.0% in the placebo group.

Professor Claus Bachert, Head of the Department of Otorhinolaryngology at Ghent University and principal investigator of these two studies, stated, “Dupixent is the first biologic therapy proven to exert a disease-modifying effect in severe CRSwNP. The drug significantly improved all disease measures assessed in the studies, including olfaction, which is one of the most troublesome and challenging symptoms for patients. Comorbid CRSwNP andAsthma"Patients with these conditions are often more difficult to treat, and the research results show that Dupixent can address both diseases in these patients, which is very encouraging."

Dupixent targets the key drivers of type 2 inflammation. Chronic rhinosinusitis with nasal polyps (CRSwNP) is an upper airway chronic disease primarily caused by type 2 inflammation, characterized by polyps that obstruct the sinuses and nasal passages. Current treatment options include intranasal corticosteroids, systemic corticosteroids, and surgery, all of which are associated with suboptimal efficacy and/or high rates of recurrence after treatment. Patients may experience severe nasal obstruction, difficulty breathing, rhinorrhea, reduced or lost sense of smell and taste, and facial pain or pressure. Persistent symptoms of CRSwNP can significantly adversely affect patients’ health-related quality of life, including reduced productivity and ability to perform activities of daily living, inability to enjoy food, sleep deprivation, and fatigue.

Dupixent is a fully human monoclonal antibody that specifically inhibits the overactivated signaling of two key proteins, IL-4 and IL-13. IL-4 and IL-13 are two inflammatory cytokines considered to be key drivers of intrinsic inflammation in allergic diseases and other type 2 inflammatory conditions, including atopic dermatitis,Asthma, eosinophilic esophagitis, grass allergy, peanut allergy, etc.

Dupixent was approved in late March 2017, becoming the first biologic agent globally for the treatment of moderate-to-severe atopic dermatitis (AD), and it has subsequently been approved for the treatment of moderate-to-severe asthma. Currently, Sanofi and Regeneron are also conducting an extensive clinical program to evaluate Dupixent for the treatment of diseases caused by allergies and other type 2 inflammatory conditions, including: atopic dermatitis in children (aged 6–11 years) (Phase III), atopic dermatitis in children (aged 6 months to 5 years) (Phase II/III), atopic dermatitis in adolescents (aged 12–17 years) (Phase III completed), and children (aged 6–11 years)Asthma(Phase III), eosinophilic esophagitis (Phase II/III), and food and environmental allergies (Phase II). In addition, the two parties plan to conduct a clinical study to evaluate the combination of Dupixent with the IL-33-targeting monoclonal antibody REGN3500. (Bioon.com)

Original Source:Positive results presented from two Phase 3 trials of Dupixent? (dupilumab) in severe chronic rhinosinusitis with nasal polyps