The Journal of the American Medical Association has published positive results from a phase 2a study of dupilumab (Sanofi/Regeneron Pharmaceuticals) in adults with moderate-to-severe chronic sinusitis with nasal polyposis who did not respond to intranasal corticosteroids.
Dupilumab is an investigational therapy that inhibits signaling of interleukin (IL)-4 and IL-13, two key cytokines required for the T helper 2 (Th2) immune response, which is believed to be a critical pathway in inflammation associated with chronic sinusitis with nasal polyps, asthma, and atopic dermatitis. The treatment is currently under clinical development, and its safety and efficacy have not been fully evaluated by any regulatory authorities.
The new study––a randomized, double-blind, placebo-controlled trial––enrolled 60 adults with chronic sinusitis with nasal polyposis that was refractory to intranasal corticosteroids. After four weeks of mometasone furoate nasal spray (MFNS) run-in, patients received subcutaneous dupilumab (300 mg) or placebo once weekly for 16 weeks, after an initial loading dose of 600 mg. All of the patients in the study continued to receive daily MFNS. Eligible patients had bilateral nasal polyposis and showed chronic symptoms of sinusitis despite treatment with an intranasal corticosteroid for at least two months. Fifty-eight percent of the patients had received prior nasal surgery for their condition. A total of 51 patients completed the study.
The least squares (LS) mean changes in the nasal polyp score were −1.9 with dupilumab and −0.3 with placebo (P <0 .001). Significant improvements with dupilumab were also observed on the 22-item SinoNasal Outcome Test (LS mean difference between groups, −18.1; P < 0.001) and on the University of Pennsylvania Smell Identification Test (UPSIT) (LS mean difference, 14.8; P < 0 .001). The most common adverse events associated with dupilumab and placebo included nasopharyngitis (47% vs. 33%, respectively), injection-site reactions (40% vs. 7%), and headache (20% vs. 17%).
Sources: Regeneron; February 2, 2016; and JAMA; February 2, 2016.