Regeneron Pharmaceuticals, Inc. and Sanofi Announces Dupixent Approved in the U.S. as the First and Only Medicine for Allergic Fungal Rhinosinusitis

Regeneron Pharmaceuticals, Inc. and Sanofi announced that the U.S. 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 our approved indications in sino-nasal diseases to now include AFRS, alongside chronic rhinosinusitis with nasal polyps.

?Allergic fungal rhinosinusitis (AFRS) is a disease that can leave both children and adults with inflamed nasal passages, nasal polyps and thick mucus causing constant nasal congestion. Some patients can also experience more serious complications like deterioration of bone around the sinuses and facial deformities,? said Kenneth Mendez, President and CEO, Asthma and Allergy Foundation of America (AAFA).

?As the first treatment specifically approved for AFRS, Dupixent offers the potential for relief to adults and children six years and older struggling with potentially debilitating symptoms.? 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. ?With this approval, Dupixent once again demonstrates its value in advancing the treatment landscape for a chronic type 2 inflammatory disease with high unmet need,? said George D. Yancopoulos, M.D., Ph.D., Board co-Chair, President and Chief Scientific Officer at Regeneron, and a principal inventor of Dupixent.

?Beyond reducing nasal signs and symptoms, Dupixent reduced the need for surgery or systemic corticosteroids with fewer patients having bone erosion in the sinuses. These results underscore its potential to establish a new standard of care for people living with AFRS. This ninth FDA approval for Dupixent, 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.?

The FDA approval is supported by the LIBERTY-AFRS-AIMS Phase 3 trial, 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 or four weeks (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 trial were similar to the known safety profile of Dupixent in CRSwNP. In pooled data from two pivotal CRSwNP trials in adults, the most common adverse reactions (=1%) in the U.S. Prescribing Information more frequently observed in patients on Dupixent compared to placebo were injection site reactions, conjunctivitis, arthralgia, gastritis, insomnia, eosinophilia, and toothache.

?Before Dupixent, people living with allergic fungal rhinosinusitis 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,? said Alyssa Johnsen, M.D., Ph.D., Global Therapeutic Area Head, Immunology Development at Sanofi. ?As the first medicine approved specifically for AFRS, Dupixent has been proven to lessen multiple signs and symptoms of disease, help break the cycle of recurrence, and reduce the risk for subsequent surgeries and corticosteroids by 92%.

We look forward to working with regulators in other countries to bring this innovative option to more patients in need.? Additional submissions are planned to other regulatory authorities around the world. About LIBERTY-AFRS-AIMS The LIBERTY-AFRS-AIMS Phase 3 trial was a randomized, double-blind, placebo-controlled trial assessing the safety and efficacy of Dupixent in adults and children aged 6 years and older with AFRS.

The 52-week trial included an age- and weight-based dose of Dupixent (300 mg every two weeks for adults and children weighing =60 kg, 200 mg every two weeks for children weighing =30 kg to <60 kg or 300 mg every four weeks for children weighing =15 kg to <30 kg) or placebo. More than 80% of patients had a history of type 2 comorbidities. The primary endpoint assessed change from baseline in sinus opacification assessed by CT scans using the Lund-Mackay score (LMK; scale: 0-24) at Week 52.

Secondary endpoints assessed at Week 24 included: Change from baseline in patient-reported nasal congestion (NC; scale: 0-3). Change from baseline in nasal polyp score (NPS; scale: 0-8) as measured by endoscopy. LMK score.

Change from baseline in patient-reported loss of smell (LoS; scale: 0-3). Some secondary endpoints were also assessed at Week 52 in addition to proportion of patients requiring surgery or systemic corticosteroids during the treatment period.