Positive results from the LIBERTY-AFRS-AIMS phase 3 study (NCT04684524) evaluating the investigational use of Dupixent (Dupilumab) in adults and children aged six years and older with allergic fungal rhinosinusitis (AFRS) demonstrated 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 are the first-ever positive phase 3 results specifically in AFRS.

Recently, the US Food and Drug Administration (FDA) accepted for priority review the supplemental Biologics Licence Application (sBLA) for Dupixent in adults and children aged six years and older with AFRS. Priority review is granted by the FDA to regulatory applications seeking approval for therapies that have the potential to provide significant improvements in the treatment, diagnosis, or prevention of serious conditions. If approved, AFRS would represent the ninth FDA-approved indication for Dupixent.

AFRS, a subtype of chronic rhinosinusitis, is a chronic type 2 inflammatory disease of the sinuses caused by an intense allergic hypersensitivity to fungi, most usually aspergillus. It primarily affects people living in warm, humid climates where fungal spores are common in the environment. It can lead to nasal polyps, nasal congestion, loss of smell, thick mucus discharge, poor health-related quality of life, bone loss around the sinus cavities, and facial deformities.

“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. This study is significant as it is the first positive phase 3 study for an investigational treatment specifically for AFRS. The ability of Dupixent to alleviate the hallmark signs and symptoms of AFRS, and to reduce the risk for surgery and corticosteroids by 92 percent, 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,” said 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, US and lead investigator of the study.

In the LIBERTY-AFRS-AIMS study, 62 adults and children aged six years and older with AFRS were randomised to receive an age- and weight-based dose of Dupixent (200 mg or 300 mg; n=33) every two or four weeks or placebo (n=29). The differences for Dupixent compared to placebo were as follows:

Primary Endpoint: Sinus opacification scores (a measure of nasal congestion as assessed by Computed Tomography [CT] scans) improved by 50 percent in the Dupixent group versus 9.8 percent in the placebo group at 52 weeks (7.36-point placebo-corrected reduction; p<0.0001); a significant reduction in sinus opacification scores was also observed at 24 weeks (p<0.0001)

Secondary Endpoints: Patient-reported nasal congestion/obstruction improved by 66.7 percent in the Dupixent group versus 25.3 percent in the placebo group at 24 weeks (0.87-point placebo-corrected reduction; p<0.0001), with continued improvement at 52 weeks to 80.6 percent in the Dupixent group compared to 11.1 percent in the placebo group (1.40-point placebo-corrected reduction; p<0.0001).

Nasal polyp size (as assessed by endoscopy) reduced by 60.8 percent in the Dupixent group compared to 15.2 percent in the placebo group at 24 weeks (2.36-point placebo-corrected reduction; p<0.0001), with continued reduction of 62.5 percent in the Dupixent group compared to 3.6 percent in the placebo group up to 52 weeks (2.77-point placebo-corrected reduction; p<0.0001).

The safety in the study was generally consistent with the known safety profile of Dupixent in its approved respiratory indications. The overall rates of Adverse Events (AEs) were 70 percent with Dupixent and 79 percent with placebo. The most common treatment-emergent AEs (>10 percent) occurring more frequently in Dupixent compared to placebo included COVID-19 (15 percent Dupixent, 14 percent placebo) and nosebleed (12 percent Dupixent, four percent placebo). Serious AEs were reported in zero percent and seven percent of patients treated with Dupixent and placebo, respectively. Additionally, AEs leading to study treatment discontinuation were reported in three percent of Dupixent patients and four percent of placebo patients.

The safety and efficacy of Dupixent in AFRS have not been fully evaluated by any regulatory authority.