Dupilumab Shows Promise for Allergic Fungal Rhinosinusitis in Phase 3 Trial, With Amber Luong, MD, PhD

At the 2025 American College of Allergy, Asthma & Immunology (ACAAI) Annual Scientific Meeting in Orlando, Florida, Amber Luong, MD, PhD, a board-certified and fellowship-trained ear, nose, and throat (ENT) specialist at UT Health Houston, presented promising phase 3 data from the LIBERTY AIMS study evaluating dupilumab (Dupixent) for allergic fungal rhinosinusitis (AFRS)—a difficult-to-treat subtype of chronic rhinosinusitis with nasal polyps (CRSwNP).

“What was unique about this study is that all current biologics that are approved for CRS with nasal polyps, all those clinical trials specifically excluded allergic fungal rhinosinusitis because it's such a unique subtype,” Luong told HCPLive during the meeting. “This is the first that specifically looked at [fungal rhinosinusitis]. It's good to see that this trial was positive, and it just introduces another treatment option in a group of patients that are very difficult to treat.”

The year-long, randomized, placebo-controlled trial specifically enrolled 62 patients meeting stringent AFRS diagnostic criteria, including characteristic computed tomography (CT) findings, presence of nasal polyps, and evidence of allergic mucin-containing fungus. Participants, some as young as 6 years old, were randomized to receive either dupilumab (200 mg or 300 mg; n = 33) every 2 or 4 weeks or placebo (n = 29) following a nasal steroid run-in period. The study’s primary endpoint was the change in nasal polyp score, with key secondary measures assessing Lund-Mackay CT sinus scores and nasal congestion severity on a 0–3 scale.

During an interview with HCPLive, Luong said these results hold promise for patients with AFS, with many experiencing significant improvement in AFRS symptoms from baseline. The trial met its primary endpoint, with sinus opacification scores improving by 50% in the dupilumab arm versus 9.8% in the placebo arm at week 52 (P <.0001). The study also observed a significant reduction in sinus opacification scores at week 24 (P <.0001).

Patients also exhibited improvement in nasal congestion or obstruction (66.7% in dupilumab arm vs 25.3% in placebo arm at week 24, P <.0001; 80.6% vs 11.6 at week 52 (P <.0001), nasal polyp size (60.8% vs 15.2%, P <.0001 at week 24; 62.5% vs 3.6% at week 52; P <.0001). She also noted a large difference from baseline in patients who needed a rescue oral corticosteroid or surgery (3% for the dupilumab arm vs 31% for the placebo arm). Patients on dupilumab had a 92% risk of systemic corticosteroid use or surgery.

“That's hugely meaningful,” Luong said. “Allergic fungal rhinosinusitis is a really unique CRS with [the] nasal polyp group. That group in general already has a subgroup of patients that are recalcitrant in terms of response to treatment, and the current treatments, excluding biologics, are surgery…oral corticosteroids or topical steroids.”

She said that meta-analyses have previously shown that the risk of recurrent surgery was roughly 28% in patients who had AFRS. Surgery can put a burden on patients, with the general anesthesia, its time, and the recovery.

“[Avoiding] any amount of surgery is very clinically meaningful,” Luong said.

Preventing a course of oral corticosteroids can be meaningful, too, she added. Oral corticosteroids may lead to long-term negative effects.

Safety outcomes mirrored dupilumab’s established profile in other type 2 inflammatory diseases, with comparable rates of mild adverse events—mainly conjunctivitis and upper respiratory infections—between treatment and placebo groups. Other adverse events in the dupilumab arm included COVID-19 (15%) and nosebleeds (12%).

If approved for this indication, Luong said dupilumab could meaningfully reshape the AFRS treatment landscape, giving clinicians a targeted, steroid-sparing option for patients living with this challenging chronic condition.

“The thought of having someone that young having to undergo repeat sinus surgery through their lifetime is a little bit disheartening, especially for those of us who have to treat it,” Luong said. “Having another treatment option available for those who get recurrent polyps really opens up the landscape in terms of treatment.”

The US Food & Drug Administration (FDA) accepted a supplemental Biologics License Application (sBLA) for the priority review of dupilumab for AFRS, with a target action date of February 28, 2026.

Reported disclosures for Luong include Stryker Corporation, GENZYME Corporation, GlaxoSmithKline, Medtronic, Regeneron Pharmaceuticals, and AstraZeneca Pharmaceuticals

References

Dupixent® (dupilumab) Pivotal Trial Met All Primary and Secondary Endpoints, Reducing Signs and Symptoms of Allergic Fungal Rhinosinusitis (AFRS); sBLA Accepted for FDA Priority Review | Regeneron Pharmaceuticals Inc. Regeneron Pharmaceuticals Inc. Published 2025. Accessed November 8, 2025. https://investor.regeneron.com/news-releases/news-release-details/dupixentr-dupilumab-pivotal-trial-met-all-primary-and-secondary