Dupixent Demonstrates Superior Efficacy Over Xolair in First Head-to-Head Respiratory Study
核心洞察
Dupixent outperformed Xolair across all primary and secondary efficacy endpoints in the EVEREST phase 4 study of 360 adults with severe chronic rhinosinusitis with nasal polyps and coexisting asthma.
The study showed Dupixent achieved superior improvements in nasal polyp size reduction (1.60-point difference), smell identification (8.0-point difference), and lung function (150 mL difference) compared to Xolair at 24 weeks.
This represents the first-ever head-to-head comparison between biologic medicines in respiratory diseases, with Dupixent demonstrating rapid improvements as early as 4 weeks across both upper and lower respiratory endpoints.
Sanofi and Regeneron Pharmaceuticals presented groundbreaking results from the EVEREST phase 4 study at the 2025 European Academy of Allergy and Clinical Immunology (EAACI) Annual Congress, demonstrating Dupixent's superiority over Xolair in treating patients with severe chronic rhinosinusitis with nasal polyps (CRSwNP) and coexisting asthma. This marks the first-ever presented head-to-head respiratory study comparing biologic medicines.
Study Design and Patient Population
The EVEREST study enrolled 360 adults with severe, uncontrolled CRSwNP and coexisting mild, moderate, or severe asthma. Patients were randomized to receive either Dupixent 300 mg every two weeks (n=181) or weight- and immunoglobulin E (IgE) level-based dosing of omalizumab every two or four weeks (n=179). Both treatments were administered alongside background mometasone furoate nasal spray.
Primary Endpoint Results
Dupixent demonstrated statistically significant superiority across both primary endpoints at 24 weeks. The treatment achieved a 1.60-point superior reduction in nasal polyp size compared to omalizumab (p<0.0001) and an 8.0-point superior improvement in patients' ability to identify different smells using the University of Pennsylvania Smell Identification Test (p<0.0001). Notably, more patients treated with Dupixent improved above the anosmia threshold compared to those receiving omalizumab.
Secondary Endpoint Outcomes
The study revealed comprehensive benefits across multiple secondary endpoints. Dupixent showed a 0.58-point superior reduction in nasal congestion/obstruction (p<0.0001) and a 0.81-point superior improvement in loss of smell (p<0.0001). Additional improvements included a 1.74-point superior reduction in symptom severity (p<0.0001), a 12.7-point difference in health-related quality of life (p<0.0001), and a 31.27-point difference in peak nasal inspiratory flow (p<0.0001).
Asthma-Related Benefits
Beyond CRSwNP improvements, Dupixent demonstrated significant benefits for coexisting asthma. Patients experienced a 150 mL difference in lung function as measured by pre-bronchodilator FEV1 (p=0.003) and a 0.48-point difference in asthma control (p<0.0001) compared to omalizumab-treated patients.
Rapid Onset of Action
A particularly notable finding was the rapid onset of improvements with Dupixent treatment. Differences between Dupixent and omalizumab were observed as early as four weeks across both CRSwNP and asthma-related endpoints, suggesting patients may experience meaningful clinical benefits relatively quickly after treatment initiation.
Safety Profile
The safety results were generally consistent with Dupixent's known safety profile in approved respiratory indications. Overall adverse event rates were similar between treatments, with 64% of Dupixent patients and 67% of omalizumab patients experiencing adverse events. Serious adverse events occurred in 2% of Dupixent patients compared to 4% of omalizumab patients, while adverse events leading to study discontinuation were reported in 3% and 1% of patients, respectively.
Clinical Significance
"Patients suffering from chronic rhinosinusitis with nasal polyps often live with the constant obstruction of their nasal passages that can lead to burdensome nasal congestion and loss of smell," said Dr. Eugenio De Corso, ENT Specialist at A. Gemelli University Hospital Foundation and lead investigator of the study. "What's more, a majority of these individuals also have asthma that can substantially impact their quality of life. 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."
Mechanism of Action
The results reinforce Dupixent's efficacy in treating both upper and lower respiratory diseases through its mechanism of targeting IL-4 (搜索) and IL-13 (搜索), two key drivers of type 2 inflammation. As a fully human monoclonal antibody that inhibits the signaling of these interleukin pathways, Dupixent addresses the underlying inflammatory processes common to both CRSwNP and asthma.
Global Impact
Dupixent has received regulatory approvals in more than 60 countries across multiple indications and is currently treating more than one million patients globally. The drug has been studied across more than 60 clinical studies involving over 10,000 patients with various chronic diseases driven by type 2 inflammation.