HOUSTON — Treatment with omalizumab (Xolair) was associated with improved endoscopic, clinical, and patient-reported outcomes in two parallel phase III studies in patients with steroid-refractory nasal polyposis.
In the POLYP 1 and POLYP 2 trials, co-primary study endpoints were met, with omalizumab-treated patients showing significant improvements at week 24, compared with placebo-treated patients, in sense of smell, congestion endoscopic nasal polyp size, post-nasal drip, runny nose, and quality of life (QoL), according to Philippe Gevaert, MD, PhD, of Ghent University in Belgium.
Treatment effects in patients treated with the biologic were observed as early as week 4 of the study, he stated in a presentation at the American College of Allergy, Asthma & Immunology annual meeting.
Gevaert also presented findings from two other companion trials showing that the biologic dupilumab (Dupixent) demonstrated clinically meaningful efficacy in the treatment of patients with chronic nasal polyps and severe asthma.
In the SINUS 24 and SINUS 52 trials, patients with asthma had worse baseline rhinosinusitis, as measured by the sinusitis symptom SNOT-22 score, and worse sense of smell than patients without asthma.
Dupilumab was approved by the FDA for the treatment of nasal polyps in June 2019. It is currently the only biologic therapy approved for this indication. Several ongoing clinical trials are examining omalizumab, and other biologics, marketed in the U.S. for the treatment of nasal polyps.
Gevaert told MedPage Today that biologic therapy has already proven to be a game changer in the treatment of patients with chronic nasal polyps and severe asthma.
“I’m a surgeon, and years ago, surgery was one of the only options in these patients. I like to do surgery, but I was doing it over and over in the same patients,” he said. “[Biologic therapy] changed that. It’s not that we don’t do surgery anymore, but we do it much less often in this specific group of severe asthma patients.”
He added that head-to-head studies of the available biologics are needed to determine if there are clinically meaningful differences in patient outcomes between the drugs.
“It is impossible to compare the studies that have been done because inclusion criteria are so different,” he said. “The world needs head-to-head comparison studies.”
Chronic rhinosinusitis with nasal polyps is an inflammatory disease characterized by loss of sense of smell, nasal obstruction, and significant QoL impairment.
Immunoglobulin E (IgE) is elevated in the tissue of patients with chronic rhinosinusitis with nasal polyps.
Patients recruited for the POLYP 1 and POLYP 2 studies had nasal polyp scores (NPS) of ≥2 in each nostril at both the initial screening and the end of the run-in period with steroid treatment and SNOT-22 scores of ≥20 at baseline.
Run-in involved treatment with nasal mometasone 200 μg BID, and patients with ≥70% adherence were considered for the study.
Co-primary endpoints included change from baseline to week 24 in NPS and changed from baseline to week 24 in average nasal congestion score (NCS). Secondary endpoints included change from baseline to week 24 in sense of smell, post-nasal drip, runny nose, and QoL, measured using validated assessment tools.
The average age of the participants for whom data were available in the two studies was around 50.
The researchers reported that the safety profile was consistent with that reported in more than 1.1 million patient-years of post-market use.
Pooled analysis of the data showed a 62.5% relative reduction in systemic steroid usage in the omalizumab group, but Gevaert noted that the number of patients needing systemic steroids was small. The difference was not statistically significant.
In the SINUS 24 and SINUS 52 trials, dupilumab treatment was associated with significant benefits over placebo in primary and secondary study endpoints.
Pooled analysis from the two trials included all patients randomized to 300 mg, given every 2 weeks, for week 24. Patients in the two studies were stratified in subgroups based on patient reported medical history of asthma. All patients also had a previous year history of systemic steroid use or polyp surgery.
Nasal congestion scores and sense of smell were significantly improved among the dupilumab-treated patients.
“You might underestimate the importance of loss of smell, but this is something that is very important for the patient,” Gevaert said. Rhinosinusitis severity scores and SNOT-22 scores were also improved in asthma and non-asthma patients on dupilumab.
“Patients in the study with asthma had a little more severe symptom profile, but we also saw that dupilumab improved those all these outcomes in these patients and it was well tolerated, ” Gevaert said.
POLYP 1 and POLYP 2 were supported by Genentech. Some co-authors are company employees.
SINUS 24 and SINUS 52 were supported by Sanofi and Regeneron.
Gevaert disclosed multiple relevant relationships with industry including Genentech, Novartis, Regeneron, Roche, Sanofi, and Stallegenes.