The Efficacy of XHANCE

Reduced symptoms were observed during a randomized, double-blind, placebo-controlled, parallel-group, multicenter study¹

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

*P≤0.05 vs EDS-placebo.²

^†P≤0.001 vs EDS-placebo.²

BID=twice daily.

CSS: Summed congestion, facial pain/pressure, and nasal discharge scores, each 0=no symptoms to 3=severe in the morning (AM); averaged over previous 7 days.
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 least squares (LS) mean difference in CSS at Week 4 was –0.7 (95% confidence interval [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.^1-3

Results shown are from ReOpen2 and are consistent with the results of non-polyp patients seen in ReOpen1 (n=122).^1,3

Coprimary endpoint: Sinus opacification in ReOpen2 (without nasal polyps) at Week 24^1,2

• 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 placebo) for XHANCE 186 mcg BID, and –5.5 (–5.9 [95% CI: –10.6, –1.3] vs placebo) for XHANCE 372 mcg BID
• 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)

Improvement in symptoms in patients who entered the trial symptomatic despite recent use of standard-delivery nasal steroids

Pooled Data From ReOpen1 and ReOpen2 (Patients Without Nasal Polyps): CSS^‡ Change From Baseline to Week 4²

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

^‡CSS: Summed congestion, facial pain/pressure, and nasal discharge scores, each 0=no symptoms to 3=severe in the morning (AM); averaged over previous 7 days.³

^§Recent use is defined as within 30 days of trial entry or less.²

Improvements in symptoms in patients who entered the trial symptomatic despite prior sinus surgery^1,2

Reduction in CSS of congestion/obstruction, facial pain/pressure, and nasal discharge²

Data From ReOpen2 (Patients Without Nasal Polyps)²

LIMITATION: This pre-planned subgroup analysis was not multiplicity adjusted; results are descriptive and should be interpreted with caution.

Data from ReOpen2 (patients without nasal polyps)

LS Mean Change From Baseline at Week 24¹

BID=twice daily; LS=least squares.

LIMITATION: This pre-planned analysis was not multiplicity adjusted; results are descriptive and should be interpreted with caution.

• Improvements in SNOT-22 scores were assessed as early as 4 weeks and continued to 24 weeks¹
• Minimal clinically important difference of –9 is considered a clinically relevant improvement^2,3

Coprimary Endpoint:

XHANCE Significantly Reduced Congestion/Obstruction in 4 Weeks^1,2

P≤0.001 vs EDS-placebo.²

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

BID=twice daily.

Coprimary Endpoint:

XHANCE Significantly Reduced Polyps in 16 Weeks^1,2

P≤0.001 vs EDS-placebo.²

^†Polyp grade was determined by the clinician using nasal endoscopy. Polyps on each side of the nose were graded on a categorical scale (0=No polyps; 1=Mild: polyps not reaching below the inferior border of the middle turbinate; 2=Moderate: polyps reaching below the inferior border of the middle concha, but not the inferior border of the inferior turbinate; 3=Severe: large polyps reaching below the lower inferior border of the inferior turbinate).¹

Baseline grade: EDS-placebo, 3.8; XHANCE 186 mcg BID, 3.9; XHANCE 372 mcg BID, 3.9.²

Secondary Endpoint:

XHANCE 372 mcg BID treatment group at Week 16²

Continued reduction in bilateral nasal polyp grade during 8-week open label extension following 16-week placebo-controlled trial. All patients received 372 mcg BID during open label extension.²

NOTE: Multiplicity adjustments were not applied for secondary endpoints; therefore, results could potentially represent chance findings.

More information on XHANCE pivotal trials

Review details of ReOpen1 and ReOpen2 in the Journal of Allergy and Clinical Immunology: In Practice

Download

Review details of NAVIGATE I and NAVIGATE II in the Journal of Allergy and Clinical Immunology

Download

NOTE: These scientific publications contain additional outcome measures and other information, including exploratory endpoints, not contained in the full Prescribing Information, which are subject to important limitations.

Two similar randomized, placebo-controlled, multicenter studies to assess XHANCE safety and efficacy in adults with nasal polyps (n=646).^1-3

NAVIGATE I: EDS-placebo, n=82; XHANCE 186 mcg BID, n=80; XHANCE 372 mcg BID, n=80. NAVIGATE II: EDS-placebo, n=79; XHANCE 186 mcg BID, n=80; XHANCE 372 mcg BID, n=82.¹

Coprimary endpoints¹:

• Improvement in nasal congestion/obstruction at Week 4
• Reduction in bilateral polyp grade at Week 16

Secondary endpoints include^2,3:

• Change from baseline in sense of smell, rhinorrhea, and facial pain or pressure through Week 12
• Subject assessment of Patient Global Impression of Change (PGIC) at Week 16
• Change in Sino-Nasal Outcome Test-22 (SNOT-22) scores at Week 16

NOTE: Multiplicity adjustments were not applied for secondary endpoints; therefore, results could potentially represent chance findings. Furthermore, open-label results may be confounded by evaluator bias.

Key inclusion criteria¹:

• Bilateral nasal polyps (grade 1 to 3)
• Moderate-to-severe symptoms of nasal congestion/obstruction

Details^2,3:

• The comparator used in the pivotal clinical studies was a liquid placebo delivered with an Exhalation Delivery System^TM (EDS^®)
• Patients and physicians remained blinded to initial treatment throughout the 8-week open-label extension
• Patients with history of allergic rhinitis could participate in the study provided their “season” did not coincide with the first 4 weeks of the study
• Subjects were allowed to use nonsedating antihistamines as “rescue” after Week 4 in an effort to reduce placebo dropout

Results shown are from NAVIGATE II and are consistent with the results seen in NAVIGATE I^2,3

• Statistically significant onset of action was generally observed within 2 weeks¹
• Continued improvement of congestion scores through Week 16 of placebo-controlled trial—NAVIGATE II²

In NAVIGATE I and NAVIGATE II, XHANCE was studied in a patient population in which¹:

• 91% had reported previous use of a nasal steroid for the treatment of nasal polyps
• 54% reported previous sinus surgery or polypectomy