The US Food and Drug Administration (FDA) has approved Dupixent (dupilumab) for the treatment of adult and pediatric patients aged 6 years and older with allergic fungal rhinosinusitis (AFRS) who have a history of sino-nasal surgery. The FDA evaluated Dupixent under priority review for the treatment of AFRS, which is reserved for medicines that have the potential to provide significant improvements in the treatment, diagnosis, or prevention of serious conditions. This approval expands the company's approved indications in sino-nasal diseases to now include AFRS, alongside chronic rhinosinusitis with nasal polyps.
AFRS is a chronic type 2 inflammatory disease. It is a specific subtype of chronic rhinosinusitis distinctly caused by an intense allergic hypersensitivity to fungi. 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, and patients can also experience bone loss around the sinus cavities and facial deformities. AFRS can be a severe and hard-to-treat form of chronic rhinosinusitis because it may not respond well to available options. Current standard-of-care treatment is surgery and prolonged courses of systemic steroids; however, disease recurrence is not uncommon.
The FDA approval is supported by the LIBERTY-AFRS-AIMS phase 3 study (clinical study identifier: NCT04684524), in which 62 adults and children aged 6 years and older with AFRS were randomized to receive an age- and weight-based dose of Dupixent (200 mg or 300 mg) every two (Q2W) or four weeks (Q4W) (n=33) or placebo (n=29). The differences for Dupixent compared to placebo were as follows: Primary endpoint: Sinus opacification scores (a measure of extent of sinus involvement by the disease as assessed by computed tomography [CT] scans) improved by 50% versus 10% at Week 52 (7.36-point placebo-corrected reduction; p<0.0001); a significant reduction in sinus opacification scores was also observed at Week 24 (p<0.0001). Secondary endpoints: Select nasal signs and symptoms: Patient-reported nasal congestion/obstruction improved by 67% versus 25% at Week 24 (0.87-point placebo-corrected reduction; p<0.0001), with continued improvement at Week 52 to 81% compared to 11% (1.40-point placebo-corrected reduction; p<0.0001).
Nasal polyp size (as assessed by endoscopy) reduced by 61% versus 15% at Week 24 (2.36-point placebo-corrected reduction; p<0.0001), with continued reduction of 63% compared to 4% up to Week 52 (2.77-point placebo-corrected reduction; p<0.0001). Sense of smell: Patient-reported loss of smell reduced by 67% versus 19% at Week 24 (0.89-point placebo-corrected reduction; p<0.0001). Treatment burden: 92% reduction in the risk of systemic corticosteroid use and/or need of surgery (29% fewer proportion of patients; p=0.0010) over 52 weeks.
3% or 0% of patients on Dupixent received systemic corticosteroids or had surgery, respectively, compared to 31% or 7% of patients on placebo. The safety results in the LIBERTY-AFRS-AIMS study were similar to the known safety profile of Dupixent in CRSwNP. In pooled data from two pivotal CRSwNP studies in adults, the most common adverse reactions (=1%) in the US Prescribing Information more frequently observed in patients on Dupixent compared to placebo were injection site reactions, conjunctivitis, arthralgia, gastritis, insomnia, eosinophilia, and toothache.
Additional submissions are planned to other regulatory authorities around the world.
