Dupixent image from Regeneron and Sanofi
On the heels of announcing positive data for Dupixent (dupilumab) in atopic dermatitis patients with darker skin tones, Sanofi and Regeneron have announced that the monoclonal antibody outperformed Xolair (omalizumab) in the phase 4 EVEREST trial. Marking the first head-to-head comparison of biologic respiratory medicines, the study focused on patients with severe chronic rhinosinusitis with nasal polyps and coexisting asthma. Results showed Dupixent led to greater improvements in nasal polyp size (1.6-point reduction), smell identification (8-point improvement), lung function (150 mL greater FEV1), and asthma control (0.48-point improvement). The 24-week trial enrolled 360 adults receiving either Dupixent 300 mg every two weeks or weight-based Xolair dosing.
Until now, doctors lacked direct comparative data to choose between these two major biologic treatments for patients with both severe sinus disease and asthma. The results carry significant commercial implications for Dupixent, which generated $14.1 billion in global sales in 2024, up 22% from the previous year, making it one of the pharmaceutical industry’s top-selling medicines. In contrast, Roche’s Xolair recorded $4 billion in 2024 sales.
The prevalence of CRSwNP is significant, affecting approximately 1.1% of patients in the U.S.
“EVEREST is the first-ever trial to demonstrate the superiority of Dupixent over Xolair on CRSwNP endpoints in patients with coexisting asthma, along with generally similar safety profiles,” said Eugenio De Corso, MD, Ph.D., the lead investigator of the study, in a statement.
“Together, these Dupixent outcomes provide important insights that will help guide patients and physicians through the treatment decision-making process.”
1. Dupixent won on all sinus-related EVEREST goals
In the EVEREST study, Dupixent met all of its primary endpoints, demonstrating superiority across all measures of chronic rhinosinusitis with nasal polyps. Patients on Dupixent experienced a 1.6-point greater reduction in nasal polyp scores compared to Xolair (p<0.0001). In addition, Dupixent had an 8-point superior improvement on the 40-point University of Pennsylvania Smell Identification Test (p<0.0001), with more patients crossing the anosmia (loss of smell) threshold to regain meaningful ability to detect odors.
The benefits extended beyond the primary endpoints to address the full spectrum of CRSwNP symptoms. Nasal congestion improved by 0.58 points more with Dupixent (p<0.0001). Loss of smell scores showed an additional 0.81-point improvement (p<0.0001), while overall symptom severity reduced by 1.74 points more than with Xolair (p<0.0001).
2. Asthma outcomes also favored Dupixent
For the coexisting asthma that affects up to 65% of severe CRSwNP patients, Dupixent demonstrated advantages over Xolair in both objective and patient-reported measures. The 150 mL greater improvement in pre-bronchodilator FEV1 (forced expiratory volume in one second) with Dupixent (p=0.003) represents a clinically meaningful difference. Improvements of 100–200 mL are clinically meaningful and associated with better breathing capacity and reduced exacerbation risk.
3. Safety profiles were comparable
The EVEREST trial revealed no major new safety concerns, with both biologics showing similar tolerability profiles that should reassure clinicians considering a switch between therapies. Overall adverse event rates were virtually identical: 64% for Dupixent versus 67% for Xolair. Meanwhile serious adverse events occurred less frequently overall, reported in 2% of Dupixent patients compared to 4% of Xolair patients. Treatment discontinuations owing to side effects remained low in both groups, affecting 3% of Dupixent patients and 1% of Xolair patients.
These safety results align with Dupixent’s established profile across its multiple approved respiratory indications, which now span seven different conditions including atopic dermatitis, asthma, chronic rhinosinusitis with nasal polyps, eosinophilic esophagitis, prurigo nodularis, chronic spontaneous urticaria, and most recently, chronic obstructive pulmonary disease.
4. The results reinforce a targeted mechanism and future growth
The comprehensive improvements across both upper and lower airways underscore Dupixent’s mechanism of targeting IL-4 and IL-13, two important drivers of type 2 inflammation. By blocking the IL-4 receptor alpha subunit, Dupixent inhibits both cytokine signaling pathways, a broader approach than Xolair’s IgE-targeting mechanism for these conditions
Sanofi and Regeneron are currently studying dupilumab in phase 3 trials for chronic pruritus of unknown origin, bullous pemphigoid, and lichen simplex chronicus, with more than 60 clinical studies completed to date involving over 10,000 patients. The companies note that dupilumab is in use by more than one million patients globally, with regulatory approvals in over 60 countries.
Filed Under: Pulmonology
