Sanofi and Regeneron’s Dupixent Shows Superiority over Xolair in First-Ever Head-to-Head Phase 4 Study in Patients with Severe Chronic Rhinosinusitis with Nasal Polyps and Co-existing Asthma
Sanofi and Regeneron Pharmaceuticals, Inc. today presented new and significant data demonstrating the superiority of Dupixent® (dupilumab) over Xolair® (omalizumab) in a first-of-its-kind, head-to-head, Phase 4 study in adults with severe chronic rhinosinusitis with nasal polyps (CRSwNP) and co-existing asthma. The study, called EVEREST, evaluated the two biologic medicines across both nasal congestion and polyp size, as well as related symptoms, health-related quality of life, and lung function in patients suffering from these challenging disorders.
The data were presented today in a late-breaking oral presentation at the 2025 European Academy of Allergy and Clinical Immunology (EAACI) Annual Congress in Glasgow, UK.
Superiority of Dupixent in All Primary and Secondary Endpoints
The EVEREST study demonstrated that Dupixent significantly outperformed Xolair across all primary and secondary endpoints related to chronic rhinosinusitis with nasal polyps — a condition often marked by persistent nasal congestion, nasal blockage, reduced or complete loss of smell (anosmia), nasal polyps, and related symptoms — alongside co-existing asthma, which further impacts patient health and their ability to perform daily routines.
Eugenio De Corso, MD, PhD, lead investigator of the study and an ENT Specialist in Otolaryngology, Head and Neck Surgery, Rhinology at A. Gemelli University Hospital Foundation in Rome, Italy, explained, “Patients suffering from chronic rhinosinusitis with nasal polyps often live with the constant obstruction of their nasal passages, nasal congestion, and a reduced ability to smell — symptoms that profoundly diminish their health-related quality of life. Furthermore, a majority of these individuals also have asthma, adding a significant additional health challenge. EVEREST is the first-ever trial to demonstrate the superiority of Dupixent over Xolair on both nasal polyp endpoints and related symptoms in patients with co-existing asthma, while retaining a generally similar safety profile. This is crucial information for guiding both patients and physicians in their treatment decisions.”
Study Design and Methodology
The EVEREST study was a Randomized, Phase 4, Head-to-Head Clinical Trial that evaluated Dupixent (dupilumab) 300mg administered every two weeks against Xolair (omalizumab) — with its dosing regimen based on patient weight and IgE (immunoglobulin E) levels — every two or four weeks in a population of 360 adults with severe, uncontrolled chronic rhinosinusitis with nasal polyps and co-existing asthma.
All patients received their respective biologic therapy in addition to standard background treatment with mometasone furoate nasal spray (MFNS). The study was designed to reflect real-world patient profiles — many of whom suffer from both upper and lower airway disease — in order to enable a more accurate understanding of their comparative effects.
Primary and Secondary Endpoints at 24 Weeks
At week 24, the study’s primary endpoints — nasal polyp size and ability to identify smells — were significantly improved in patients treated with Dupixent when contrasted with omalizumab:
- Nasal polyp size was 1.60 points greater in reduction with Dupixent (p < 0.00011).
- Sense of smell was 8.0 points greater in improvement with Dupixent (p < 0.00011), with a greater number of patients experiencing an improvement above the anosmia threshold.
Additionally, Dupixent demonstrated superiority over omalizumab across numerous secondary endpoints:
- Nasal congestion or obstruction improved by 0.58 points more with Dupixent (p < 0.00011).
- Loss of smell saw a greater improvement by 0.81 points with Dupixent (p < 0.00011).
- Overall symptom severity was 1.74 points greater in improvement with Dupixent (p < 0.00011).
- The health-related quality of life score improved by 12.7 points more with Dupixent (p < 0.00012).
- The peak nasal inspiratory flow improved by 31.27 points more with Dupixent (p < 0.00012).
- Overall severity of rhinosinusitis was 1.87 points greater in improvement with Dupixent (p < 0.00012).
Asthma-Related Outcomes
The study also evaluated the effects on asthma control and lung function in this patient population with co-existing asthma:
- Lung function (pre-bronchodilator FEV1) improved by 150 mL more with Dupixent than with omalizumab (p = 0.0032).
- The asthma control score improved by 0.48 points more with Dupixent (p < 0.00012), reflecting greater symptom control.
This further underscores the ability of Dupixent to provide comprehensive disease control in patients battling both upper and lower airway disease.
Safety Profile
Safety results were generally consistent with the well-established profile of both biologics in their respective approved respiratory indications:
- The rate of adverse events (AEs) was similar between groups, with 64% for Dupixent and 67% for omalizumab.
- Serious adverse events were somewhat lower in Dupixent (2%) than in omalizumab (4%).
- Adverse events leading to study discontinuation were reported in 3% of Dupixent recipients and 1% in omalizumab recipients.
Overall, the EVEREST study highlights the strong and consistent superiority of Dupixent over omalizumab in improving both nasal and asthma symptoms with a similar safety profile.
The EVEREST study marks a significant step forward in understanding the comparative benefits of biologic treatments for patients with severe chronic rhinosinusitis with nasal polyps and co-existing asthma — a population with high disease burden and complex treatment needs. The data suggest that Dupixent may enable more effective symptom control and a greater improvement in health-related quality of life for these patients, adding depth to clinician decision-making in choosing the most appropriate biologic for their care.
