FDA Approves Dupilumab for Chronic Rhinosinusitis With Nasal Polyps

Dupilumab (Dupixent) has gained FDA approval for the treatment of chronic rhinosinusitis with nasal polyps, marking the first biologic approved for adults with inadequately controlled disease.

Chronic rhinosinusitis with nasal polyps is a chronic disease of the upper airway that obstructs the sinuses and nasal passages and can lead to breathing difficulties, nasal congestion and discharge, reduced or loss of smell and taste, and facial pressure.

“Nasal polyps can lead to loss of smell and often patients require surgery to remove the polyps,” said Sally Seymour, MD, director of the Division of Pulmonary, Allergy, and Rheumatology Products in the FDA’s Center for Drug Evaluation and Research, in a statement. “Dupixent provides an important treatment option for patients whose nasal polyps are not adequately controlled with intranasal steroids.”

The monoclonal antibody inhibits the signaling of interleukin-4 and interleukin-13, 2 proteins that play a central role in type 2 inflammation. It is the first treatment to shrink nasal polyp size and improve the signs and symptoms of associated chronic rhinosinusitis with nasal polyps compared with placebo.

These results were demonstrated throughout the 24-week SINUS-24 and 52-week SINUS-52 trials consisting of 724 patients aged 18 years and older with nasal polyps who were symptomatic despite taking intranasal corticosteroids.

In both trials, which are part of the phase 3 LIBERTY clinical trial program, patients received either dupilumab 300 mg every 2 weeks with standard of care mometasone furoate nasal spray or placebo plus mometasone furoate nasal spray.

At 24 weeks, patients receiving dupilumab experienced a 57% and 51% improvement in nasal congestion/obstruction severity compared with a 19% and 15% improvement with placebo in SINUS-24 and SINUS-52, respectively. Patients on the biologic experienced a 33% and 27% reduction in their nasal polyps score while patients on placebo had a 7% and 4% increase.

Secondary endpoints—improvement in sinus opacification and loss of smell—also favored dupilumab. At 24 weeks, patients on the biologic experienced a 42% and 27% improvement in sinus opacification compared with 4% and 0% with placebo in SINUS-24 and SINUS-52, respectively. There was a 52% and 45% improvement in loss of smell associated with dupilumab compared with a 12% and 10% improvement with placebo.

At 52 weeks, a pre-specified pooled analysis of the 2 trials revealed that dupilumab resulted in a significant reduction of systemic corticosteroid use and the need for sino-nasal surgery compared with placebo.

Many patients with nasal polyps also have other type 2 inflammatory diseases, such as asthma, and are more difficult to treat. Among the 59% of patients who also had asthma in the 2 clinical trials, the improvements in lung function were similar to that seen in patients in the dupilumab asthma program.

Throughout the trials, adverse events that occurred in at least 2% of patients and occurred more frequently with dupilumab than with placebo included injection site reactions (6% vs 4%), conjunctivitis (2% vs 1%), arthralgia (3% vs 2%), and gastritis (2% vs 1%).