Results Show Reductions in Sinus Opacification With Dupilumab for Allergic Fungal Rhinosinusitis

Positive results from the pivotal LIBERTY-AFRS-AIMS (NCT04684524) phase 3 study evaluating the investigational use of dupilumab (Dupixent) in adults and children 6 years and older with allergic fungal rhinosinusitis (AFRS) demonstrated significant improvements in signs and symptoms of disease across all primary and secondary endpoints, including reductions in sinus opacification, nasal congestion, and nasal polyps compared to placebo. These findings represent the first-ever positive phase 3 results specifically in AFRS.¹

The FDA accepted the supplemental biologics license application for dupilumab in this population for priority review, which is granted for therapies with the potential to offer significant improvements in treating serious conditions. The target action date is February 28, 2026, and if approved, AFRS would mark the ninth FDA-approved indication for dupilumab.¹

“People with allergic fungal rhinosinusitis live with persistent nasal obstruction, congestion, and polyps that can place a great strain on their day-to-day lives. With limited treatment options, uncontrolled symptoms can progress to serious complications like the buildup of thick mucus that may require surgery, bony erosion of the sinuses, and facial deformities,” Amber U. Luong, MD, PhD, FACS, professor and vice chair for academic affairs in the Department of Otorhinolaryngology at the McGovern Medical School of the University of Texas Health Science Center at Houston, Texas, said in a news release.¹

Understanding AFRS and Dupilumab

AFRS is a chronic type 2 inflammatory disease of the sinuses caused by intense allergic hypersensitivity, most typically to the fungus Aspergillus. It is considered a unique subset within chronic rhinosinusitis with nasal polyps (CRSwNP), and the condition is characterized by chronic inflammation, nasal polyposis, and the production of thick eosinophilic mucin. The disease often leads to expansile changes of the involved sinus cavities, potentially resulting in bony erosion or facial deformities.^1,2

AFRS is often challenging to treat because it does not respond well to currently available options. Standard-of-care involves meticulous sinus surgery to clear the eosinophilic mucin, followed by maintenance therapy with postoperative steroids; however, the rate of disease recurrence remains high.^1,2

Dupilumab is a fully human monoclonal antibody designed to inhibit the signaling of the IL-4 and IL-13 pathways. These interleukins are considered 2 central drivers of the Type 2 inflammation that underlies AFRS. Dupilumab is not an immunosuppressant.¹

The drug is currently approved for multiple chronic type 2 inflammatory diseases and is used alone or in combination with other medicines. Approved indications include treatment for moderate-to-severe atopic dermatitis, moderate-to-severe asthma (adjunctive therapy), CRSwNP (adjunctive therapy), eosinophilic esophagitis, prurigo nodularis, chronic spontaneous urticaria, bullous pemphigoid, and inadequately controlled chronic obstructive pulmonary disease with high blood eosinophils (adjunctive therapy).³

Key Data on Efficacy and Safety

The pivotal LIBERTY-AFRS-AIMS study was a randomized, double-blind, placebo-controlled phase 3 study including 62 adults and children aged 6 years and Dupilumab with AFRS. Patients were randomized to receive an age- and weight-based dose of Dupixent (n = 33) or placebo (n = 29) for 52 weeks. The patient population included more than 80% with a history of type 2 comorbidities. The duration of the study lasted for 2 to 4 weeks of screening, 52 weeks of treatment, and 12 weeks of follow-up.^1,4

Investigators found that sinus opacification scores, measured by computed tomography scans using the Lund-Mackay score (scale: 0-24), showed significant improvement. At 52 weeks, the scores improved by 50.0% in the dupilumab group compared with 9.8% in the placebo group, and a significant reduction was also observed at 24 weeks. Additionally, patients treated with dupilumab experienced a 92% lower risk of requiring systemic corticosteroids and/or surgery compared to placebo over 52 weeks.¹

Furthermore, patient-reported nasal congestion/obstruction (scale: 0-3) improved by 80.6% in the dupilumab group compared with 11.1% in the placebo group at 52 weeks. Nasal polyp size (scale: 0-8, assessed by endoscopy) reduced by 62.5% in the dupilumab group compared with 3.6% in the placebo group up to 52 weeks.¹

The safety profile of dupilumab in the AFRS study was generally consistent with its known profile in approved respiratory indications. Overall rates of adverse events (AEs) were 70% with dupilumab and 79% with placebo. Serious AEs were reported in 0% of patients treated with dupilumab and 7% of patients treated with placebo. AEs leading to study treatment discontinuation were infrequent, with 3% of patients receiving dupilumab and 4% of patients receiving the placebo reporting discontinuation. The most common treatment-emergent AEs (≥10%) occurring more frequently in the dupilumab group compared with the placebo included COVID-19 (15% vs 14%, respectively) and nosebleed (12% vs 4%, respectively).¹

“This study is significant as it is the first positive phase 3 study for an investigational treatment specifically for AFRS,” Luong said in the news release.¹ “The ability of Dupixent to alleviate the hallmark signs and symptoms of AFRS, and to reduce the risk for surgery and corticosteroids by 92%, provide the strongest evidence to date that IL4 and IL13 are key drivers of the type 2 inflammation leading to this disease, as they seem to be for multiple other type 2 inflammatory diseases.”

READ MORE: Respiratory Resource Center

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REFERENCES

1. Press Release: ACAAI: Sanofi and Regeneron’s Dupixent pivotal study met all primary and secondary endpoints, reducing signs and symptoms of allergic fungal rhinosinusitis; sBLA accepted for FDA priority review. News release. Sanofi. November 7, 2025. Accessed November 13, 2025. https://www.sanofi.com/en/media-room/press-releases/2025/2025-11-07-13-00-00-3183599

2. Liu MY, Chen PG, Weitzel EK, Lopez EM. Allergic Fungal Rhinosinusitis: A Contemporary Update. Ear Nose Throat J. Published online June 9, 2025. doi:10.1177/01455613251346578

3. Mayo Clinic. Dupilumab (subcutaneous route). Updated September 1, 2025. Accessed November 13, 2025. https://www.mayoclinic.org/drugs-supplements/dupilumab-subcutaneous-route/description/drg-20406153

4. Dupilumab in allergic fungal rhinosinusitis (AFRS) (LIBERTY-AFRS-AI). ClinicalTrials.gov identification: NCT04684524. May 30, 2025. Accessed November 13, 2025. https://clinicaltrials.gov/study/NCT04684524?term=NCT04684524&rank=1