Philippe Gevaert1, Rebecca Saenz2, Jonathan Corren3, Joseph K Han4, Joaquim Mullol5, Stella E Lee6, Randall A Ow7, Rui Zhao8, Monet Howard9, Kit Wong8, Lutaf Islam10, Monica Ligueros-Saylan11, Theodore A Omachi8, Claus Bachert12. 1. Upper Airway Research Laboratory, Department of Otorhinolaryngology, Ghent University Hospital, Ghent, Belgium. 2. Genentech, Inc, South San Francisco, Calif. Electronic address: saenz.rebecca@gene.com. 3. Departments of Medicine and Pediatrics, David Geffen School of Medicine at UCLA, Los Angeles, Calif. 4. Eastern Virginia Medical School, Norfolk, Va. 5. Rhinology Unit & Smell Clinic, ENT Department, Hospital Clinic, IDIBAPS, Universitat de Barcelona, CIBERES, Barcelona, Catalonia, Spain. 6. Department of Otolaryngology-Head and Neck Surgery, University of Pittsburgh Medical Center, Pittsburgh, Pa. 7. Sacramento Ear, Nose and Throat Surgical and Medical Group, Inc, Sacramento, Calif. 8. Genentech, Inc, South San Francisco, Calif. 9. Roche, Mississauga, Ontario, Canada. 10. Roche, Welwyn Garden City, United Kingdom. 11. Novartis Pharmaceuticals Corporation, East Hanover, NJ. 12. Upper Airway Research Laboratory, Department of Otorhinolaryngology, Ghent University Hospital, Ghent, Belgium; Division of ENT Diseases, CLINTEC, Karolinska Institute, Stockholm, Sweden; First Affiliated Hospital, Sun Yat-sen University, International Airway Research Center, Guangzhou, China.
Abstract
BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) frequently remains uncontrolled despite maximal medical therapy and sinonasal surgery, presenting several unmet needs and challenges. Omalizumab previously demonstrated efficacy in CRSwNP in duplicate phase 3, randomized, placebo-controlled trials (POLYP 1, POLYP 2). OBJECTIVE: This open-label extension evaluated the continued efficacy, safety, and durability of response of omalizumab in adults with CRSwNP who completed POLYP 1 or 2. METHODS: After 24 weeks of omalizumab or placebo in POLYP 1 and 2, patients (n = 249) received open-label omalizumab plus background nasal mometasone therapy for 28 weeks and were subsequently followed for 24 weeks after omalizumab discontinuation. Efficacy end points assessed change from baseline for the coprimary end points, Nasal Polyp Score and Nasal Congestion Score, and the secondary end points of Sino-Nasal Outcome Test 22, Total Nasal Symptom Score and its components, and University of Pennsylvania Smell Identification Test scores. Safety objectives included incidence of adverse events and adverse events leading to omalizumab discontinuation. RESULTS: Patients who continued omalizumab experienced further improvements across coprimary end points and secondary end points through 52 weeks. Patients who switched from placebo to omalizumab experienced favorable responses across end points through week 52 that were similar to POLYP 1 and 2 at week 24. After omalizumab discontinuation, scores gradually worsened over the 24-week follow-up, but remained improved from pretreatment levels for both groups. The safety profile was similar to previous reports. CONCLUSIONS: The efficacy and safety profile from this study supports extended omalizumab treatment up to 1 year for CRSwNP with inadequate response to nasal corticosteroids.
BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) frequently remains uncontrolled despite maximal medical therapy and sinonasal surgery, presenting several unmet needs and challenges. Omalizumab previously demonstrated efficacy in CRSwNP in duplicate phase 3, randomized, placebo-controlled trials (POLYP 1, POLYP 2). OBJECTIVE: This open-label extension evaluated the continued efficacy, safety, and durability of response of omalizumab in adults with CRSwNP who completed POLYP 1 or 2. METHODS: After 24 weeks of omalizumab or placebo in POLYP 1 and 2, patients (n = 249) received open-label omalizumab plus background nasal mometasone therapy for 28 weeks and were subsequently followed for 24 weeks after omalizumab discontinuation. Efficacy end points assessed change from baseline for the coprimary end points, Nasal Polyp Score and Nasal Congestion Score, and the secondary end points of Sino-Nasal Outcome Test 22, Total Nasal Symptom Score and its components, and University of Pennsylvania Smell Identification Test scores. Safety objectives included incidence of adverse events and adverse events leading to omalizumab discontinuation. RESULTS: Patients who continued omalizumab experienced further improvements across coprimary end points and secondary end points through 52 weeks. Patients who switched from placebo to omalizumab experienced favorable responses across end points through week 52 that were similar to POLYP 1 and 2 at week 24. After omalizumab discontinuation, scores gradually worsened over the 24-week follow-up, but remained improved from pretreatment levels for both groups. The safety profile was similar to previous reports. CONCLUSIONS: The efficacy and safety profile from this study supports extended omalizumab treatment up to 1 year for CRSwNP with inadequate response to nasal corticosteroids.