FDA Accepts Dupilumab sBLA for Chronic Rhinosinusitis with Nasal Polyps

The US Food and Drug Administration (FDA) has accepted the supplemental Biologics License Application (sBLA) for dupilumab (Dupixent) as a therapy for adults with inadequately controlled severe chronic rhinosinusitis with nasal polyps (CRSwNP).

The sBLA—which was also granted Priority Review designation by the FDA—will decided on by June 26. The Sanofi-Regeneron biologic has been previously approved by the FDA to treat adults with moderate-to-severe atopic dermatitis not well controlled with topical prescription therapy, as well as for maintenance treatment of moderate-to-severe asthma in patients aged 12 years or older.

This indication would mark the interleukin (IL) 4 and 13-pathway inhibitor as the first biologic approved by the FDA to treat CRSwNP. Like current and potential therapies investigated for treatment with dupilumab, CRSwNP is a chronic condition driven by type 2 inflammation. Patients experience severe nasal obstruction that causes breathing difficulties, nasal discharge, reduction or loss of smell and taste, among other symptoms.

Dupilimab’s sBLA is supported by data from a pair of phase 3 pivotal trials evidencing its efficacy and safety as a combination therapy in patients with recurring severe CRSwNP after failed invasive/corticosteroid treatment. The studies, presented at the American Academy of Allergy, Asthma & Immunology (AAAAI) 2019 Annual Meeting in San Francisco, CA, last month, included a patient population that mostly (about 60%) suffered from co-morbid asthma.

In an interview with MD Magazine® while at the AAAAI 2019 meeting, SINUS-24 study author Joseph Han, MD, Medical Director of the Division of Allergy, Eastern Virginia Medical School, explained how the 276-patient, randomized trial comparing 300 mg subcutaneous dupilumab to placebo over 24 weeks showed treated patients had significantly improved scores for nasal polyp and congestion.

“A lot of these patients came in and they had moderate to severe nasal congestion,” Han explained. “By the end of the study, the patients had zero to mild nasal congestion—so they were able to meet the co-primary endpoints for the clinical study.”

In assessment for treatment of symptoms including change or loss of smell—a symptom which Han emphasized as being among the most crucial to CRSwNP patients—investigators showed dupilumab was even capable of returning patients’ sense of smell by study’s end.

Han called this finding remarkable, “because that increases our (patients’) quality of life tremendously.”

Sanfoi-Regeneron are also currently investigating dupilumab as a therapy for adolescent and pediatric AD, pediatric asthma, eosinophilic esophagitis, and food and environmental allergies, and is also planning a future assessment of the drug for chronic obstructive pulmonary disease (COPD).

Neil Graham, MD, MPH, vice president of Strategic Program Direction, Immunology & Inflammation for Regeneron, told MD Mag at AAAAI 2019 that the science of applying biologic mechanism of action has progressed greatly in the past decade. Now, he believes dupilumab is position well to reach most of the indications the companies are pursuing for it.

“Now, this is I think no longer just a hypothesis—because we have an indication for atopic dermatitis driven by IL-4 and 13, for type 2 asthma driven by IL-4 13 and now CRS (chronic rhinosinusitis) with it nasal polyps,” Graham said. “We always felt that would be the real proof of the pudding, because you have essentially 3 different conditions in the same patient, all of which we think are type 2—and we now know are type 2 because dupilumab works for all of them.”