Dupilumab Improved Outcomes in Patients With Chronic Rhinosinusitis, Nasal Polyps
The drug showed significant improvement on every primary and secondary endpoint in those who had failed treatment with surgery and/or systemic corticosteroids.
A pair of phase 3 trials have demonstrated that dupilumab (Dupixent, Regeneron and Sanofi), when added to the standard-of-care corticosteroid nasal spray, improved chronic sinus disease, comorbid asthma outcome, nasal congestion severity and polyp size, and sense of smell, for adults with recurring severe chronic rhinosinusitis with nasal polyps (CRSwNP), despite previous treatment with surgery and/or systemic corticosteroids.
Regeneron Pharmaceuticals and Sanofi announced the results of the trials, SINUS-24 and SINUS-52, at the 2019 Annual Meeting of the American Academy of Allergy, Asthma & Immunology (AAAAI) in San Francisco.
The trials also found that dupilumab reduced the need for nasal/sinus surgery and systemic corticosteroid use in these patients, according to the 2 companies.
The drug is the first biologic therapy to demonstrate the potential to produce disease-modifying effects in severe CRSwNP, Claus Bachert, MD, professor and head of clinics of the Department of Otorhinolaryngology at Ghent University in Belgium, and principal investigator of the trials, said in a statement.
Dupilumab significantly improved all disease measures in the study, including sense of smell, one of the most challenging-to-treat symptoms for patients, he said.
Dupilumab is a human monoclonal antibody specifically designed to inhibit signaling of interleukin-4 and interleukin-13 (IL-4 and IL-13). The findings from the 2 trials, as well as from prior trials in asthma and atopic dermatitis, demonstrate that these are 2 key proteins that play a central role in type 2 inflammation, which seems to underlie CRSwNP, as well as several other allergic diseases.
The 24-week SINUS-24 and 52-week SINUS-52 trials evaluated the drug every 2 weeks with standard-of-care mometasone furoate nasal spray (MFNS) compared with a placebo injection plus MFNS. SINUS-52 also included a third patient group, which switched from dupilumab every 2 weeks to dupilumab every 4 weeks, after the primary endpoint was assessed at week 24.
Topline results for both trials were announced in October 2018. These trials met their coprimary endpoints of change from baseline in nasal congestion/obstruction severity and change from baseline in nasal polyps score, measured at 24 weeks.
Data presented at AAAAI showed that dupilumab significantly reduced chronic sinus disease in both trials. Treatment effects from the drug began as early as 4 weeks with progressive improvement up to 24 weeks in SINUS-24, a 24-week trial, and up to 52 weeks in SINUS-52. Both trials evaluated dupilumab treatment every 2 weeks for up to 24 weeks, and after week 24 through 52 weeks, SINUS-52 included a group of patients treated every 4 weeks, in addition to a group treated every 2 weeks.
Overall, rates of adverse events were generally similar between the dupilumab-treated group and the placebo.
Dupilumab is FDA-approved for treatment of adult patients with moderate-to-severe atopic dermatitis that is not well controlled by topical prescription therapies or who cannot use topical therapies. The drug is also approved in the United States for use with other asthma medicines for maintenance treatment of moderate-to-severe asthma in people 12 years and older with an eosinophilic phenotype or with oral corticosteroid dependent asthma.
Positive results presented from two phase 3 trials of Dupixent ® (dupilumab) in severe chronic rhinosinusitis with nasal polyps (CRSWNP) [news release]. Tarrytown, New York, and Paris, France; February 25, 2019: Regeneron. newsroom.regeneron.com/news-releases/news-release-details/dupixentr-dupilumab-showed-positive-topline-results-two-phase-3. Accessed February 25, 2019.