Treatment with dupilumab significantly improved outcomes for adults with allergic fungal rhinosinusitis (AFRS), based on new data presented at the American College of Allergy, Asthma, and Immunology (ACAAI) 2025 Annual Meeting.

The new study focused specifically on AFRS, a type of chronic rhinosinusitis for which no previous treatment was approved, said lead investigator Amber U. Luong, MD, 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, Houston, in an interview. 

AFRS can cause signs and symptoms not seen in other types of chronic rhinosinusitis, such as thick mucus discharge, bone loss around the sinus cavities, and facial deformities, said Luong. “The data with dupilumab are the first-ever positive phase 3 results specifically in allergic fungal rhinosinusitis,” she said.

Dupilumab, a fully human monoclonal antibody, inhibits the signaling of the interleukin 4 (IL-4) and IL-13 pathways. Dupilumab has been approved for a range of other conditions including chronic obstructive pulmonary disease, chronic rhinosinusitis with nasal polyps, eosinophilic esophagitis, and bullous pemphigoid.

In the phase 3 LIBERTYAFRS-AIMS study, the researchers randomized 62 individuals aged 6 years and older with symptoms of AFRS to dupilumab or a placebo. All adults and adolescents weighing 60 kg or more received 300 mg every 2 weeks. Children and adolescents weighing between 30 kg and 60 kg received 200 mg every 2 weeks, while those weighing between 15 kg and 30 kg received 300 mg every 4 weeks. 

The mean age of the participants was 39.8 years, 27% were female. The primary endpoint was a significant change from baseline in Lund-Mackay CT, a radiological measure of blockage or inflammation in the paranasal sinuses.

After 52 weeks, significantly more patients in the dupilumab group met the primary endpoint, with a least squares mean (LSM) change from baseline of -9.17, compared to -1.81 in the placebo group (P < .0001). 

Patients treated with dupilumab also showed significant improvement compared with placebo patients across secondary endpoints including reductions in nasal polyps and nasal congestion, with LSM differences of -2.77 and -1.40, respectively, between the treatment and placebo groups from baseline to 52 weeks (P < .0001 for both). 

In addition, significantly fewer patients in the dupilumab group were treated with systemic corticosteroids or underwent surgery compared to the placebo group (3% vs 31%).

Overall safety profiles were similar between the dupilumab and placebo groups. The proportion of patients with any treatment-emergent adverse events 69.7% and 78.6%, respectively. However, no treatment-emergent serious adverse events were reported in the dupilumab group, and only two were reported in the placebo group.

The FDA has accepted the supplemental biologics license application for dupilumab in adults and children aged 6 years and older with AFRS for priority review. 

Data Support Extending Indication 

The findings were in line with the researchers’ expectations, given dupilumab’s approval for chronic rhinosinusitis with nasal polyps, and the shared underlying disease mechanism of both conditions, Luong said. Therefore, “it wasn’t surprising to see that inhibiting IL-4 and IL-13 with dupilumab resulted in significant improvements in signs and symptoms of disease, across all primary and secondary endpoint measures, compared to placebo,” she said. 

In the absence of approved treatments for AFRS specifically, patients are often managed with surgery followed by oral and/or topical corticosteroids, Luong said. However, disease recurrence can occur, meaning patients might need repeat surgeries or prolonged courses of corticosteroids, she said. “If approved, dupilumab would be the first medicine specifically indicated for AFRS, and it has already shown its potential to reduce key nasal signs and symptoms of disease and lower the risk of systemic corticosteroid use and/or need for surgery in this pivotal trial,” she added. 

The study met all primary and secondary endpoints at trial sites in multiple countries around the world where AFRS is predominant, Luong told Medscape Medical News. Given the relatively small trial size, the real-world impact of dupilumab on the disease will be interesting to understand if the indication is approved, she noted.

The study was supported by Sanofi and Regeneron Pharmaceuticals. 

Luong disclosed serving on advisory boards for companies including GlaxoSmithKline, AstraZeneca, Amgen, Regeneron and Sanofi. Her institution also receives received research funding associated with participation in clinical trials sponsored by Sanofi, GSK, Eli Lily, and Insmed.