FDA Approves Dupilumab for Treatment of AFRS, a Subtype of Chronic Rhinosinusitis

The FDA approved dupilumab (Dupixent; Sanofi, Regeneron) for the treatment of adult and pediatric patients 6 years and older with allergic fungal rhinosinusitis (AFRS) who have a history of sinonasal surgery.¹

“Before [dupilumab], people living with AFRS had to rely on treatments that left them potentially vulnerable to regrowth of nasal polyps and thick mucus that could rob them of their sense of smell,” Alyssa Johnsen, MD, PhD, global therapeutic area head for Immunology and Oncology Development at Sanofi, said in a news release.¹

Dupilumab is a fully human monoclonal antibody that inhibits the signaling of the IL-4 and IL-13 pathways. Unlike other treatments, it is not an immunosuppressant. Dupilumab has demonstrated significant clinical benefit in decreasing type 2 inflammation in phase 3 studies, establishing that IL-4 and IL-13 are 2 of the key and central drivers, which play a role in multiple related and comorbid diseases.

Dupilumab received approvals in 1 or more indications, including certain patients with atopic dermatitis, asthma, chronic rhinosinusitis with nasal polyps, chronic obstructive pulmonary disease, and chronic spontaneous urticaria, among others.²

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 warmer, humid climates, where fungal spores are common. This 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. Currently, the standard of care treatment involves surgery and prolonged courses of systemic steroids; however, disease recurrence can still occur.²

Clinical Data Supporting the Use of Dupilumab in AFRS

Dupilumab’s efficacy was supported by LIBERTY-AFRS-AI (NCT04684524), a randomized, double-blind, placebo-controlled, parallel-group phase 3 trial that assessed the efficacy and safety of dupilumab in patients with AFRS. The trial included a 2- to 4-week screening period, 52 weeks of randomized investigational intervention period, and 12 weeks of follow-up.³

A total of 62 patients 6 years and older were randomly assigned to receive treatment with dupilumab (n = 33) or matched placebo (n = 29) for a 52-week duration. Dupilumab doses were age- and weight-based (300 mg every 2 weeks for adults and children ≥60 kg, 200 mg every 2 weeks for children ≥30 to <60 kg, and 300 mg every 4 weeks for children weighing ≥15 kg to <30 kg).^3,4

The trial’s primary end point was Lund-Mackay computed tomography score (range 0-24), and secondary end points were nasal polyp score (range 0-8), nasal congestion score (NC, range 0-3), need for systemic corticosteroids and/or surgery, and safety. Results were published in November 2025 in Annals of Allergy, Asthma & Immunology.^3,4

The findings indicated that sinus opacification scores—a measure of nasal congestion as assessed by CT scans—improved by approximately 50.0% in patients receiving dupilumab compared with only 9.8% in the placebo group (7.36-point placebo-corrected reduction; P < .0001). Significant reductions in sinus opacification scores were also observed at 24 weeks (P < .0001), the investigators wrote.^1,2,4

Patient-reported NC improved by approximately 66.7% in the dupilumab group compared with 25.3% in the placebo group at 24 weeks (0.87-point placebo-corrected reduction; P < .0001), with improvements continuing at the 52-week point to 80.6% and 11.1%, respectively (1.40-point placebo-corrected reduction; P < .0001).^1,2,4

Nasal polyp size was also reduced by 60.8% and 15.2% in these respective groups at 24 weeks (2.36-point placebo-corrected reduction; P < .0001), and 62.5% and 3.6% at 52 weeks (2.77-point placebo-corrected reduction; P < .0001). There was a 92% lower risk of systemic corticosteroid use and/or needing surgery in the dupilumab group vs placebo (29.1% fewer proportion of patients; P = .0010) over 52 weeks.^1,2,4

The safety in the study was generally consistent with the known safety profile of dupilumab in its approved respiratory indications. Of note, the number of patients experiencing treatment-emergent adverse events (TEAEs) was similar between the dupilumab (69.7%) and placebo (78.6%) groups.^2,4 Specifically, the most common TEAEs (>10%) occurring more frequently in dupilumab compared with placebo included COVID-19 (15% dupilumab, 14% placebo) and nosebleed (12% dupilumab, 4% placebo).^1,2,4

Serious TEAEs were reported in 0% and 7% of patients treated with dupilumab and placebo, respectively. Additionally, AEs that directly led to study treatment discontinuation were reported in approximately 3% and 4% of patients treated with dupilumab and placebo, respectively.^1,2

“With this approval, [dupilumab] once again demonstrates its value in advancing the treatment landscape for a chronic type 2 inflammatory disease with high unmet need. Beyond reducing nasal signs and symptoms, [dupilumab] reduced the need for surgery or systemic corticosteroids, with fewer patients having bone erosion in the sinuses,” George D. Yancopoulos, MD, PhD, board cochair, president, and chief scientific officer at Regeneron, said in the news release.

“These results underscore its potential to establish a new standard of care for people living with AFRS. This ninth FDA approval for [dupilumab], the most widely used innovative branded antibody medicine, strengthens the established efficacy and body of evidence that IL-4 and IL-13 are major drivers of type 2 inflammation across many chronic diseases.”¹

REFERENCES

1. Dupixent (dupilumab) approved in the U.S. as the first and only medicine for allergic fungal rhinosinusitis (AFRS). News release. Regeneron. February 24, 2026. Accessed February 24, 2026. https://investor.regeneron.com/news-releases/news-release-details/dupixentr-dupilumab-approved-us-first-and-only-medicine-allergic

2. 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 February 23, 2026. https://www.sanofi.com/en/media-room/press-releases/2025/2025-11-07-13-00-00-3183599

3. Dupilumab in allergic fungal rhinosinusitis (AFRS) (LIBERTY-AFRS-AI). ClinicalTrials.gov. Updated December 22, 2025. Accessed February 23, 2026. https://clinicaltrials.gov/study/NCT04684524

4. Luong A, Levy J, Wise S, et al. Dupilumab efficacy in adults and children aged 6 and over with allergic fungal rhinosinusitis (LIBERTY-AIMS). Ann Allergy Asthma Immunol. 2025;135(5 suppl 1):S100-S101. doi:10.1016/j.anai.2025.08.297