FDA Approves Dupilumab for Severe CRSwNP

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

The biologic monoclonal antibody from Sanofi-Regeneron—which was previously granted Priority Review for its application—has been previously approved to provide maintenance therapy to patients aged 12 years or older with moderate to severe asthma, as well as for the treatment of moderate to severe atopic dermatitis in improperly-treated adult patients.

With the newest indication, dupilumab has become the first biologic approved by the FDA to treat patients with CRSwNP.

Similar to the other conditions currently and potentially treated with biologics such as dupilumab, CRSwNP is a chronic condition driven by type 2 inflammation. Symptoms including breathing difficulties, nasal discharge, and even loss of smell or taste are prevalent among patients who experience severe nasal obstruction.

In a recent interview with MD Magazine® while at the American Thoracic Society (ATS) 2019 Annual Meeting in Dallas, TX, pivotal phase 3 SINUS-24 and SINUS-52 trials study author Stella Lee, MD, explained that CRSwNP’s greatest symptom is an impaired quality of life.

“These patients suffer greatly from loss of smell, they can't breathe, they can't taste,” Lee, director of Sino-Nasal Disorders & Allergy at the University of Pittsburgh, said. “Their nose has taken over their lives—imagine if you had a cold that never went away, compounded by times 100.”

Prior to dupilumab, patients had no deterrent for their symptoms—let alone a therapy that could end them altogether. Lee noted she met patients with CRSwNP who had gone a decade without smelling, tasting, or properly breathing. After 1 week of dupilumab, their senses were returning.

“When you meet a patient who has not been able to smell or breathe for a decade, you wonder, ‘Is surgery even going to help them? I don't think even oral steroids are going to help them’,” Lee said. “It's been incredibly promising for me to see that, and exciting for our patients.”

Dupilumab is an interleukin 4 (IL4) and 13-pathway inhibitor which more directly targets and treats the process associated with type 2 inflammation. Its benefit for CRSwNP was evidenced in the pair of phase 3 SINUS trials, in which patients were randomized to either differing regimens of 300 mg dupilumab or placebo.

At 24 weeks, patients receiving therapy reported significant improvements in upper airway measures including nasal peak inspiratory flow and 22-item Sino-Nasal Outcome Test (SNOT) score, versus those administered placebo.

Patients receiving dupilumab also reported significant improvements in lower airway outcomes including forced expiratory volume at 1 second (FEV₁) and mean score on the six-item Asthma Control Questionnaire score, versus those administered placebo at the same observed time period.

Common adverse events (>5% of all patients) included nasal polyps, headache, nasopharyngitis, injection site erythema, asthma, and epistaxis.

Other ongoing investigations for dupilumab include its candidacy as a therapy for pediatric and adolescent atopic dermatitis, pediatric asthma, eosinophilic esophagitis, food and environmental allergies, and—potentially—chronic obstructive pulmonary disease (COPD).

Seeing as these conditions are believed to be driven by type 2 inflammation, and that dupilumab is now indicated for a trio of type 2 conditions, company leaders such as Neil Graham, MD, MPH, vice president of Regeneron’s Strategic Program Direction, Immunology & Inflammation, are anticipating continued success.

“The science has come a long way just in the last 9 years I've been working in the area,” Graham told MD Mag. “And this drug is positioned, we think very nicely, to meet most of those indications, potentially.”