SAN FRANCISCO — The biologic therapy dupilumab (Dupixent) showed significant efficacy with a good safety profile in a phase III study involving patients with chronic rhinosinusitis with multiple nasal polyps, researchers reported here.
Compared to dupilumab-treated patients, patients in the placebo group of the randomized trial were three times more likely to require nasal polyp surgery or treatment with systemic steroids after week 24, said Joseph K. Han, MD, of Eastern Virginia Medical School in Norfolk.
Han presented new data from the SINUS-24 trial, sponsored by dupilumab’s manufacturers, in a late-breaking abstract session of the American Academy of Allergy, Asthma and Immunology annual meeting.
“The severity of symptoms that these patients experience is often underappreciated by physicians,” he said. “If you look at Quality of Life questionnaires in patients with chronic sinusitis with nasal polyps it is very similar to that of patients with COPD and congestive heart failure.”
He noted that many patients lose their sense of smell and report near constant nasal blockage.
Dupilumab is a monoclonal antibody that targets the IL-4 alpha receptor protein, which means it blocks both IL-4 and IL-13 pathways that drive type 2 inflammation.
Last fall, the FDA approved the drug for use in asthma patients 12 and older with eosinophilic asthma and patients with oral corticosteroid-dependent asthma. The drug was previously approved for use in adults with moderate-to-severe atopic dermatitis not controlled with topical medications.
Chronic rhinosinusitis with nasal polyps is a predominantly type 2 inflammatory disease, with IL-4, IL-5, and IL-13 as prominent cytokines and tissue infiltration by eosinophils, lymphocytes, basophils, and mast cells.
Han noted that in phase II trials, dupilumab showed significant efficacy in reducing polyp burden when given as an add-on therapy with the nasal anti-inflammatory spray mometasone furoate, which is used to reduce nasal polyp growth.
The phase III trial included patients with severe chronic rhinosinusitis with nasal polyps with and without comorbid asthma who were using intranasal mometasone daily and who had also received previous treatment with systemic corticosteroids and/or surgery.
All patients had at least five nasal polyps and a minimum of two polyps in each nostril.
A total of 5,276 patients were randomized 1:1 to treatment with subcutaneous dupilumab 300 mg or placebo every two weeks for 24 weeks in addition to mometasone.
Key outcomes included change from baseline to week 24 in nasal polyp score (NPS), patient-reported nasal congestion, CT Lund-Mackay (LMK), UPSIT smell test, SNOT-22 sinus Quality of Life questionnaire, FEV1, and ACQ-6 scores.
Least square mean differences favored dupilumab over placebo for NPS (by 22.06 points), nasal congestion (20.89), LMK (27.44), UPSIT (10.56), and SNOT-22 (221.12), at P<0.0001 for all.
Dupilumab treatment also significantly reduced systemic corticosteroid use/nasal polyp surgery. In comorbid asthma patients (58.3% of the sample), it improved lung function as measured with FEV1 and also improved ACQ-6 scores for asthma control.
At week 24, 65% of patients on dupilumab had improved by 1 or more point in NPS and 46.2% had improved by 2 or more points, compared to 17.3% and 4.5%, respectively, in the placebo group (P<0.0001).
Treatment with dupilumab reduced the proportion of patients requiring systemic corticosteroids and/or sinus surgery by 73% and it was also associated with meaningful improvements in lung function and asthma control in patients with comorbid asthma.
The most common adverse event occurring at higher frequency with dupilumab was epistaxis (7.7% vs 3.0% placebo).
The trial was sponsored by Sanofi and Regeneron Pharmaceuticals.
Han disclosed a financial relationship with Sanofi Genzyme.