The Efficacy of XHANCE

Pooled data endpoints from ReOpen1 and ReOpen2²:

• CSS change at Week 4 for patients who were symptomatic (met entry criteria) despite using a standard-delivery nasal steroid at trial entry
• Frequency of acute exacerbations^||

Reduced composite symptom score observed during a randomized, double-blind, placebo-controlled, parallel-group, multicenter study.¹

Coprimary Endpoint: Change From Baseline at Week 4 in Composite Symptom Score (CSS) in ReOpen2 (Without Nasal Polyps)^1,2

*P≤0.05 vs EDS-placebo. ^†P≤0.001 vs EDS-placebo.

Results after Week 4 not multiplicity adjusted; results were descriptive and should be interpreted with caution.

CSS: Sum of scores averaged as rated by the patient in the morning immediately prior to next dose over 7 days for the above symptoms (0=no symptoms to 3=severe; CSS range 0-9). Mean baseline CSS was 6.2, 5.9, and 6.0, respectively, for EDS-placebo, XHANCE 186 mcg, and XHANCE 372 mcg. At Week 4, CSS was -0.8, -1.5, and -1.7, respectively, for EDS-placebo, XHANCE 186 mcg, and XHANCE 372 mcg. The LS mean difference in CSS at Week 4 was -0.7 (95% CI: -1.3, -0.2) in the XHANCE 186 mcg group vs EDS-placebo, and -0.9 (95% CI: -1.5, -0.4) in the XHANCE 372 mcg group vs EDS-placebo.^1,2

Study design summary: Patients randomized 1:1:1 to receive XHANCE 186 mcg BID, XHANCE 372 mcg BID or placebo, nasally for 24 weeks. Patients had at least 2 active nasal symptoms with a minimum nasal congestion score ≥1.5 out of 3 and a baseline CT scan showing ≥25% opacification of both ethmoid and at least 1 maxillary sinus.¹

Coprimary endpoint: Sinus opacification in ReOpen2 (without nasal polyps) at Week 24

• LS mean change from baseline in percent opacified sinus volume was 0.4 for EDS-placebo, -7.0 (-7.5 [95% CI: -12.1, -2.8] vs EDS-placebo) for XHANCE 186 mcg BID, and -5.5 (-5.9 [95% CI: -10.6, -1.3] vs EDS-placebo) for XHANCE 372 mcg BID¹
• Baseline mean percent opacified sinus volume scores were 64.1% for EDS-placebo (n=75), 60.5% for XHANCE 186 mcg BID (n=72), and 61.5% for XHANCE 372 mcg BID (n=73)¹

BID=twice daily; CI=confidence interval; CSS=Composite Symptom Score; EDS=Exhalation Delivery System; LS=least squares.

Pooled data from ReOpen1 and ReOpen2 (Patients without nasal polyps):
CSS* change from baseline at Week 4⁵

With Recent Use of a Standard-Delivery Steroid^†

CSS LIMITATION: Use of a standard-delivery nasal steroid 30 days prior to study entry was patient-reported and compliance was not confirmed.

*Core symptoms of chronic sinusitis are defined as congestion/obstruction, facial pain/pressure, and nasal discharge.¹

^†Using at least one standard nasal spray at trial entry.^1,4

BID=twice daily; CSS=Composite Symptom Score; EDS=Exhalation Delivery System; LS=least squares.

This analysis was not adjusted for multiplicity; results are descriptive and should be interpreted with caution.

*Data were pooled to assess the incidence of acute exacerbations of CRS, defined as a worsening of symptoms that required escalation of treatment (eg, antibiotics, oral steroids, acute care visits).^1,2,5

^†IRR for XHANCE 186 mcg BID: 0.44; (95% CI 0.23); not controlled for multiplicity.²

^‡IRR for XHANCE 372 mcg BID: 0.34 (95% CI: 0.2, 0.7; P=0.002) vs EDS-placebo; type I error-controlled analysis.⁵

ReOpen1 included 332 patients with CRS with or without nasal polyps and ReOpen2 included 223 patients with CRS without nasal polyps.¹

XHANCE is the first and only medication shown to reduce the risk of occurrence of acute exacerbations of CRS without polyps^1,6,7

In the subgroup of patients without nasal polyps from ReOpen1 and ReOpen2, the rate of acute exacerbations of CRS was reduced by 53% among patients in both XHANCE treatment groups vs placebo. This was derived from an IRR of 0.47 (95% CI: 0.2, 1.1) and 0.47 (95% CI: 0.2, 1.1) among patients using XHANCE 186 mcg (n=113) and 372 mcg (n=112) twice daily vs placebo, respectively; the difference was not statistically significant.¹

IRR=incidence rate ratio.

Coprimary Endpoint: Change From Baseline at Week 4 in Nasal Congestion in NAVIGATE II (Patients With Nasal Polyps)

*Least-squares mean change from baseline in patient-reported AM instantaneous daily scores for nasal symptoms on a scale from 0-3 (0=none, 1=mild, 2=moderate, 3=severe).¹

The majority of patients in the NAVIGATE II trial had ≥1 polyp grade reduction at Week 16 with both XHANCE 186 mcg (n=80) and 372 mcg (n=82) BID doses. XHANCE 186 BID: 63.0% (OR 2.32); XHANCE 372 mcg BID: 69.1% (OR 3.09).⁸

P<0.001 vs EDS-placebo.

Trial results

• Onset of action was generally observed within 2 weeks^1,8
• Continued improvement of congestion scores through week 16 of placebo-controlled trial—NAVIGATE II⁸
• Statistically significant reduction in bilateral polyp grade at Week 16¹

Study design summary: 16-week, randomized, double-blind, parallel-group, multicenter, placebo-controlled trials in adults ≥18 years with CRS with nasal polyps and moderate-to-severe nasal congestion. Patients received 186 mcg or 372 mcg XHANCE BID or placebo BID. Coprimary efficacy endpoints: 1) Change from baseline to Week 4 in nasal congestion/obstruction averaged over preceding 7 days of treatment and 2) change from baseline to Week 16 in bilateral polyp grade. Congestion rated by patient on 4-point severity scale (0=none, 1=mild, 2=moderate, 3=severe) immediately prior to next dose. Polyps determined by nasal endoscopy: 0=No polyps; 1=Mild: polyps not reaching below inferior border of middle turbinate; 2=Moderate: polyps reaching below inferior border of middle concha, but not inferior border of inferior turbinate; 3=Severe: large polyps reaching below lower inferior border of inferior turbinate.¹

BID=twice daily; OR=odds ratio.