Adult Patients 18 Years of Age and Older

The safety and efficacy of XOLAIR was evaluated in two, randomized, multicenter, double-blind, placebo-controlled clinical trials (CRSwNP Trial 1 [NCT03280550] and CRSwNP Trial 2 [NCT03280537]) that enrolled patients with chronic rhinosinusitis with nasal polyps (CRSwNP) with inadequate response to nasal corticosteroids (CRSwNP Trial 1, n=138; CRSwNP Trial 2, n=127). Patients received XOLAIR or placebo SC every 2 or 4 weeks, with XOLAIR dosage and frequency according to Table 3, for 24 weeks followed by a 4-week follow-up period. All patients received background nasal mometasone therapy during both the treatment period and during a 5-week run-in period. Prior to randomization, patients were required to have evidence of bilateral polyps as determined by a nasal polyp score (NPS) ≥ 5 with NPS ≥ 2 in each nostril, despite use of nasal mometasone during the run-in period. NPS was measured via endoscopy and scored (range 0-4 per nostril: 0= no polyps; 1=small polyps in the middle meatus not reaching below the inferior border of the middle turbinate; 2=polyps reaching below the lower border of the middle turbinate; 3=large polyps reaching the lower border of the inferior turbinate or polyps medial to the middle turbinate; 4=large polyps causing complete obstruction of the inferior nasal cavity) for a total NPS (range 0-8). Patients were furthermore required to have a weekly average of nasal congestion score (NCS) > 1 prior to randomization, despite use of nasal mometasone. Nasal congestion was measured by a daily assessment on a 0 to 3 point severity scale (0=none, 1=mild, 2=moderate, 3=severe). Prior sino-nasal surgery or prior systemic corticosteroid usage were not required for inclusion in the trials and sinus CT scans were not performed to evaluate for sinus opacification. Demographics and baseline characteristics, including allergic comorbidities, are described in Table 14.

The co-primary endpoints in CRSwNP Trials 1 and 2 were NPS and average daily NCS at Week 24. In both trials, patients who received XOLAIR had a statistically significant greater improvement from baseline at Week 24 in NPS and weekly average NCS, than patients who received placebo. Results from CRSwNP Trials 1 and 2 are shown in Table 15.

The greater improvements in NPS and NCS in the XOLAIR group compared to the placebo group were observed as early as the first assessment at Week 4 in both studies, as seen in Figure 1.

The mean NPS and NCS at each study week by treatment group is shown in Figure 1.

XOLAIR had statistically significant improvements on sense of smell score compared to placebo. Sense of smell was measured by a daily assessment on a 0 to 3 point severity scale (0=no symptoms, 1=mild symptoms, 2=moderate symptoms, 3=severe symptoms). The LS mean difference for change from baseline at Week 24 in sense of smell score in XOLAIR compared to placebo was -0.3 (95% CI: -0.6, -0.1) in CRSwNP Trial 1 and -0.5 (95% CI: -0.7, -0.2) in CRSwNP Trial 2.

XOLAIR had statistically significant improvements on post-nasal drip compared to placebo. The LS mean difference for change from baseline at Week 24 in post-nasal drip score in XOLAIR compared to placebo was -0.6 (95% CI: -0.8, -0.3) in CRSwNP Trial 1 and -0.5 (95% CI: -0.8, -0.3) in CRSwNP Trial 2.

XOLAIR had statistically significant improvements on runny nose compared to placebo. The LS mean difference for change from baseline at Week 24 in runny nose score in XOLAIR compared to placebo was -0.4 (95% CI: -0.7, -0.2) in CRSwNP Trial 1 and -0.6 (95% CI: -0.9, -0.4) in CRsWNP Trial 2.

In a pre-specified pooled analysis of systemic corticosteroid use during the 24-week treatment period, there was no significant reduction in systemic corticosteroid use between the treatment arms. The proportion of patients taking systemic corticosteroid in XOLAIR was 2.3% compared to 6.2% in placebo. The odds-ratio of systemic corticosteroid use with XOLAIR compared to placebo was 0.4 (95% CI: 0.1, 1.5).

There were no sino-nasal surgeries reported, in either placebo or XOLAIR arms, in either Trial.