EVEREST: Dupilumab (Dupixent) Outperforms Omalizumab (Xolair) for CRSwNP, Asthma

Regeneron Pharmaceuticals and Sanofi have announced positive results from the EVEREST phase 4 trial in adults with severe chronic rhinosinusitis with nasal polyps (CRSwNP) and coexisting asthma, highlighting dupilumab (Dupixent)’s superiority to omalizumab (Xolair) for all primary and secondary efficacy endpoints of CRSwNP, and in all asthma-related endpoints.1

The data represent the first-ever presented head-to-head respiratory trial with biologic medicines and were shared in a late-breaking oral presentation at the 2025 European Academy of Allergy and Clinical Immunology (EAACI) Annual Congress.1

“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. What’s more, a majority of these individuals also have asthma that can substantially impact their quality of life,” Eugenio De Corso, MD, PhD, ENT Specialist, Otolaryngology, Head and Neck Surgery, Rhinology, A. Gemelli University Hospital Foundation, IRCSS, Rome, Italy, and lead investigator of the study, said in a press release.1 “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. Together, these Dupixent outcomes provide important insights that will help guide patients and physicians through the treatment decision-making process.”

A fully human monoclonal antibody, dupilumab inhibits the signaling of the interleukin-4 (IL-4) and interleukin-13 (IL-13) pathways and is not an immunosuppressant. Its clinical development program has shown significant clinical benefit and a decrease in type 2 inflammation in phase 3 trials, establishing IL-4 and IL-13 as 2 key and central drivers of the type 2 inflammation that plays a major role in multiple related and often comorbid diseases.1

Dupilumab has received regulatory approvals in > 60 countries in 1 or more indications. In 2018, it was granted US Food and Drug Administration approval for the treatment of moderate-to-severe asthma. In 2019, it was approved for the treatment of adults with uncontrolled CRSwNP, which was later expanded in 2024 to include adolescents 12-17 years of age.2,3,4

A randomized, double-blind phase 4 trial, EVEREST compared the efficacy and safety of dupilumab to omalizumab in adults with severe, uncontrolled CRSwNP and coexisting mild, moderate or severe asthma. During the 24-week trial, patients received dupilumab 300 mg every 2 weeks or omalizumab 75 to 600 mg every 2 or 4 weeks, which was added to background MFNS. Omalizumab dosing was determined based on body weight and serum total IgE levels as per the approved label.1

The primary endpoints assessed change from baseline in nasal polyp score and the University of Pennsylvania Smell Identification Test. Secondary endpoints included change from baseline in nasal congestion, loss of smell, total symptom score, Sino-Nasal Outcome Test-22, peak nasal inspiratory flow, and rhinosinusitis disease severity. Other endpoints assessed pre-bronchodilator forced expiratory volume over one second and the 7-item Asthma Control Questionnaire.1

Primary and secondary endpoint results in CRSwNP for patients treated with dupilumab compared to omalizumab at 24 weeks were as follows, with differences seen as early as 4 weeks:

• 1.60-point superior reduction in nasal polyp size (P <.0001)
• 8.0-point superior improvement in ability to identify different smells (P <.0001)
• 0.58-point superior reduction in nasal congestion/obstruction (P <.0001)
• 0.81-point superior improvement in loss of smell (P <.0001)
• 1.74-point superior reduction in symptom severity (P <.0001)
• 12.7-point difference in health-related quality of life (P <.0001)
• 31.27-point difference in peak nasal inspiratory flow (P <.0001)
• 1.87-point difference in overall severity of rhinosinusitis (P <.0001)

Asthma endpoint results for patients treated with dupilumab compared to omalizumab at 24 weeks were as follows, with differences again seen as early as 4 weeks:

• 150 mL difference in lung function (pre-bronchodilator FEV1; P = .003)
• 0.48-point difference in asthma control (P <.0001)

According to a press release from Regeneron, the safety results in the EVEREST trial were consistent with the known safety profile of dupilumab in its approved respiratory indications, with similar overall rates of adverse events (AEs) observed between dupilumab (64%) and omalizumab (67%). Serious AEs were reported in 2% and 4% of patients treated with dupilumab and omalizumab, respectively.AEs leading to trial discontinuation were reported in 3% of dupilumab patients and 1% of omalizumab patients.1

References

1. Regeneron. Dupixent® (dupilumab) Demonstrated Superiority Over Xolair® (Omalizumab) in Chronic Rhinosinusitis with Nasal Polyps (CRSwNP) in Patients with Coexisting Asthma in First-ever Presented Phase 4 Head-to-Head Respiratory Trial. June 15, 2025. Accessed June 18, 2025. https://investor.regeneron.com/news-releases/news-release-details/dupixentr-dupilumab-demonstrated-superiority-over-xolairr

2. Regeneron. FDA Approves Asthma Indication for Dupixent® (dupilumab). October 19, 2018. Accessed June 18, 2025. https://investor.regeneron.com/news-releases/news-release-details/fda-approves-asthma-indication-dupixentr-dupilumab

3. FDA Approves Dupixent® (dupilumab) for Chronic Rhinosinusitis with Nasal Polyposis. June 26, 2019. Accessed June 18, 2025. https://investor.regeneron.com/news-releases/news-release-details/fda-approves-dupixentr-dupilumab-chronic-rhinosinusitis-nasal

4. Smith T. FDA Approves Dupilumab for Adolescents with Chronic Rhinosinusitis with Nasal Polyps. HCPLive. September 13, 2024. Accessed June 18, 2025. https://www.hcplive.com/view/fda-approves-dupilumab-for-adolescents-chronic-rhinosinusitis-with-nasal-polyps