The Efficacy of XHANCE

Icon representing symptoms of nasal congestion and obstruction from CRS with nasal polyps

Coprimary endpoint:

XHANCE significantly reduced congestion/obstruction in 4 weeks1,2

Graphic of reduced congestion/obstruction in 4 weeks using a 0-3 point scale: 0.24 EDS-placebo (n=79); 0.68 XHANCE 186 mcg BID (n=80); 0.62 XHANCE 372 mcg BID (n=82); P<0.001 vs EDS-placeboGraphic of reduced congestion/obstruction in 4 weeks using a 0-3 point scale: 0.24 EDS-placebo (n=79); 0.68 XHANCE 186 mcg BID (n=80); 0.62 XHANCE 372 mcg BID (n=82); P<0.001 vs EDS-placebo

*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 BID=twice daily.

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

NAVIGATE I and NAVIGATE II were double-blind, placebo-controlled trials lasting 16 weeks with an 8-week open-label extension in patients with bilateral nasal polyps and moderate to severe congestion. All patients received XHANCE 372 mcg BID during the open-label extension.1-3

 

XHANCE trial design & details

XHANCE is a corticosteroid indicated for the treatment of nasal polyps in patients 18 years of age or older.

XHANCE has been extensively studied in over 1500 patients.1-5

646 patients with bilateral nasal polyps evaluated for efficacy and safety for up to 24 weeks2,3

  • NAVIGATE I and NAVIGATE II were double-blind, placebo-controlled trials lasting 16 weeks with an 8-week open-label extension in patients with bilateral nasal polyps and moderate to severe congestion. All patients received XHANCE 372 mcg BID during the open-label extension1-3

928 patients with chronic sinusitis with and without nasal polyps in 2 open-label trials evaluated for safety for up to 12 months1,4

  • EXHANCE-3 and EXHANCE-12 were open-label studies lasting 3 months (n=705) and 12 months (n=223)1,4
 
   
 

NAVIGATE I and NAVIGATE II: Phase 3 trials evaluating efficacy and safety

Two similar randomized, placebo-controlled, multicenter studies to assess XHANCE safety and efficacy (n=646)1

Flow chart showing the study design and clinical trial format for NAVIGATE I and NAVIGATE II Flow chart showing the study design and clinical trial format for NAVIGATE I and NAVIGATE II

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 include2,3:

  • Change from baseline in sense of smell, rhinorrhea, and facial pain or pressure
  • 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

Details2,3,5:

  • The comparator used in the pivotal clinical studies was a liquid placebo delivered with an Optinose Exhalation Delivery System (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

EXHANCE-3 and EXHANCE-12: Phase 3 open-label studies

Data demonstrating safety for up to 1 year were also evaluated in 2 open-label studies in 928 patients with chronic sinusitis (CS) with or without nasal polyps.1,4*

Graphic showing EXHANCE-3 and EXHANCE-12 study design Graphic showing EXHANCE-3 and EXHANCE-12 study design

Key inclusion criteria4:

  • CS with or without nasal polyps*
  • Experiencing ≥2 defining symptoms of CS

*XHANCE is not indicated to treat CS.

References:
  1. Full Prescribing Information for XHANCE (fluticasone propionate). OptiNose US, Inc.; 2023.
  2. Leopold DA, Elkayam D, Messina JC, et al. NAVIGATE II: randomized, double-blind trial of the exhalation delivery system with fluticasone (EDS-FLU) for nasal polyposis. J Allergy Clin Immunol. 2019;143(1):126-134.
  3. Sindwani R, Han JK, Soteres DF, et al. NAVIGATE I: randomized, placebo-controlled, double-blind trial of the Exhalation Delivery System with fluticasone for chronic rhinosinusitis with nasal polyps. Am J Rhinol Allergy. 2019;33(1):69-82.
  4. Palmer JN, Jacobson KW, Messina JC, et al. EXHANCE-12: 1-year study of the exhalation delivery system with fluticasone (EDS-FLU) in chronic rhinosinusitis. Int Forum Allergy Rhinol. 2018;8(8):869-876.
  5. Data on file. OptiNose US, Inc.

Post hoc subgroup analysis

CONGESTION/OBSTRUCTION REDUCTION IN PATIENTS PREVIOUSLY USING STANDARD NASAL STEROIDS1,2

Reductions in congestion/obstruction at Week 4 in the subgroup of patients reporting standard nasal steroid use prior to study entry1,2

In a subgroup of patients reporting use of a standard nasal steroid within 30 days of the screening visit1:

  • Patients reported a mean treatment duration of 3 years with a standard nasal steroid
  • The improvements in this subgroup were similar in magnitude to improvements in overall study population
  These post hoc results are descriptive and should be interpreted with caution.

Post hoc analysis of NAVIGATE I and II
Pooled subgroup data (n=218)

Bar chart showing change in congestion score Bar chart showing change in congestion score

*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 BID=twice daily.

IMPORTANT SAFETY INFORMATION
WARNINGS AND PRECAUTIONS:
  • Local Nasal Effects: epistaxis, erosion, ulceration, septal perforation, Candida albicans infection, and impaired wound healing. Monitor patients periodically for signs of possible changes on the nasal mucosa. Avoid use in patients with recent nasal ulcerations, nasal surgery, or nasal trauma until healing has occurred.
Please see additional Important Safety Information and full Prescribing Information, including Instructions for Use.
References:
  1. Senior BA, Schlosser RJ, Bosso J, Soler ZM. Efficacy of the exhalation delivery system with fluticasone in patients who remain symptomatic on standard nasal steroid sprays. Int Forum Allergy Rhinol. 2021;11(5):837-845.
  2. Full Prescribing Information for XHANCE (fluticasone propionate). OptiNose US, Inc.; 2023.
 

 

 

Icon representing symptoms of facial pain/pressure from CRS with nasal polyps

Coprimary endpoint:

XHANCE significantly reduced polyps in 16 weeks1,2

Graphic of reduced polyps in 16 weeks: 0.61 EDS-placebo (n=79); 1.22 XHANCE 186 mcg BID (n=80); 1.41 XHANCE 372 mcg BID (n=82); P<0.001 vs EDS-placeboGraphic of reduced polyps in 16 weeks: 0.61 EDS-placebo (n=79); 1.22 XHANCE 186 mcg BID (n=80); 1.41 XHANCE 372 mcg BID (n=82); P<0.001 vs EDS-placebo

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

*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</sup

Secondary endpoint:

XHANCE 372 mcg BID treatment group at Week 162

Secondary endpoint:

Graphic of about 7 out of 10 patients experienced a ≥1-point reduction in bilateral polyp grade vs 40% with EDS-placeboGraphic of about 7 out of 10 patients experienced a ≥1-point reduction in bilateral polyp grade vs 40% with EDS-placebo

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

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

Post hoc subgroup analysis

POLYP REDUCTION IN PATIENTS WITH AND WITHOUT PRIOR SINUS SURGERY1

Reduction in bilateral nasal polyp score at Week 16 in the subgroups of patients with or without prior sinus surgery1

  • A post hoc analysis of a pooled population from NAVIGATE I and NAVIGATE II analyzed reduction in bilateral polyp grade in the subgroup of patients who had sinus surgery and those who did not have sinus surgery prior to study entry1
  • Patients were excluded from the studies if they had a history of sinus or nasal surgery within 6 months before screening2,3

  The results shown below are descriptive and should be interpreted with caution.

Post hoc analysis of NAVIGATE I and II
Pooled data (n=481)

Polyp grade criteria Polyp grade criteria

Baseline grade: EDS-placebo, 3.9; XHANCE 186 mcg BID, 4.0; XHANCE 372 mcg BID, 3.9.1-3

Polyp grade criteria Polyp grade criteria

Baseline grade: EDS-placebo, 3.7; XHANCE 186 mcg BID, 3.8; XHANCE 372 mcg BID, 3.7.1

 
IMPORTANT SAFETY INFORMATION
WARNINGS AND PRECAUTIONS:
  • Local Nasal Effects: epistaxis, erosion, ulceration, septal perforation, Candida albicans infection, and impaired wound healing. Monitor patients periodically for signs of possible changes on the nasal mucosa. Avoid use in patients with recent nasal ulcerations, nasal surgery, or nasal trauma until healing has occurred.

Please see additional Important Safety Information and full Prescribing Information, including Instructions for Use.

References:
  1. Data on file. OptiNose US, Inc.
  2. Leopold DA, Elkayam D, Messina JC, et al. NAVIGATE II: randomized double-blind trial of the exhalation delivery system with fluticasone (EDS-FLU) for nasal polyposis. J Allergy Clin Immunol. 2019;143(1):126-134.
  3. Sindwani R, Han JK, Soteres DF, et al. NAVIGATE I: randomized, placebo-controlled, double-blind trial of the Exhalation Delivery System with fluticasone for chronic rhinosinusitis with nasal polyps. Am J Rhinol Allergy. 2019;33(1):69-82.
 

Post hoc subgroup analysis

POLYP REDUCTION IN PATIENTS PREVIOUSLY USING STANDARD NASAL STEROIDS1

Reductions in nasal polyp grade at Week 16 in the subgroup of patients reporting standard nasal steroid use prior to study entry1

In a subgroup of patients reporting use of a standard nasal steroid within 30 days of the screening visit1:

  • Patients reported a mean treatment duration of 3 years with a standard nasal steroid
  • The improvements in this subgroup were similar in magnitude to improvements in overall study population

  These post hoc results are descriptive and should be interpreted with caution.

Post hoc analysis of NAVIGATE I and II
Pooled subgroup data (n=218)

Bar chart showing change in bilateral polyp grade Bar chart showing change in bilateral polyp grade

*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 reached 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 turbinate1

IMPORTANT SAFETY INFORMATION
WARNINGS AND PRECAUTIONS:
  • Local Nasal Effects: epistaxis, erosion, ulceration, septal perforation, Candida albicans infection, and impaired wound healing. Monitor patients periodically for signs of possible changes on the nasal mucosa. Avoid use in patients with recent nasal ulcerations, nasal surgery, or nasal trauma until healing has occurred.

Please see additional Important Safety Information and full Prescribing Information, including Instructions for Use.

Reference:
  1. Senior BA, Schlosser RJ, Bosso, J, Soler ZM. Efficacy of the exhalation delivery system with fluticasone in patients who remain symptomatic on standard nasal steroid sprays. Int Forum Allergy Rhinol. 2020.
 

POLYP GRADE CRITERIA

How polyps were graded in NAVIGATE I and NAVIGATE II

The bilateral polyp grade scale ranges from 0 (no polyp) to 6 (severe bilateral nasal polyposis). Baseline grade in NAVIGATE II: EDS-placebo, 3.8; XHANCE 186 mcg BID, 3.9; XHANCE 372 mcg BID, 3.9.1  
Animated illustration showing polyps classified as grade 1, 2, and 3
  Polyp grade was determined by using nasoendoscopy and was based on extent of polyp tissue mass at the moment of observation relative to unequally spaced anatomic landmarks in 1 dimension1-3:
  • 0=no polyps
  • 1=not below the inferior border of the middle turbinate
  • 2=below the inferior border of the middle turbinate but not the inferior border of the inferior turbinate
  • 3=below the lower inferior border of the inferior turbinate
 
References:
  1. Leopold DA, Elkayam D, Messina JC, et al. NAVIGATE II: randomized, double-blind trial of the exhalation delivery system with fluticasone (EDS-FLU) for nasal polyposis. J Allergy Clin Immunol. 2019;143(1):126-134.
  2. Sindwani R, Han JK, Soteres DF, et al. NAVIGATE I: randomized, placebo-controlled, double-blind trial of the Exhalation Delivery System with fluticasone for chronic rhinosinusitis with nasal polyps. Am J Rhinol Allergy. 2019;33(1):69-82.
  3. Data on file. OptiNose US, Inc.
 

Icon representing symptoms of nasal congestion and obstruction from CRS with nasal polyps

Improvement in all 4 defining symptoms of nasal polyps1,4,5

Symptom improvement was observed irrespective of prior corticosteroid and/or surgical treatment.1,4

Coprimary endpoint:

Graphic of improved congestion 2.5X Improvement vs EDS-placebo after 4 weeks LS mean change from baseline: EDS-placebo=–0.24, XHANCE 372 mcg BID=–0.62Graphic of improved congestion 2.5X Improvement vs EDS-placebo after 4 weeks LS mean change from baseline: EDS-placebo=–0.24, XHANCE 372 mcg BID=–0.62

Secondary endpoints:

Graphic of improved sense of smell 27% improvement after 16 weeks (vs 9.7% with EDS-placebo) LS mean change from baseline: EDS-placebo=–0.24, XHANCE 372 mcg BID=–0.63; reduced facial pain/pressure 56% reduction after 16 weeks (vs 33% with EDS-placebo) LS mean change from baseline: EDS-placebo=–0.48, XHANCE 372 mcg BID=–0.75; reduced nasal discharge (rhinorrhea) 47% reduction after 16 weeks (vs 23% with EDS-placebo) LS mean change from baseline: EDS-placebo=–0.42, XHANCE 372 mcg BID=–0.84Graphic of improved sense of smell 27% improvement after 16 weeks (vs 9.7% with EDS-placebo) LS mean change from baseline: EDS-placebo=–0.24, XHANCE 372 mcg BID=–0.63; reduced facial pain/pressure 56% reduction after 16 weeks (vs 33% with EDS-placebo) LS mean change from baseline: EDS-placebo=–0.48, XHANCE 372 mcg BID=–0.75; reduced nasal discharge (rhinorrhea) 47% reduction after 16 weeks (vs 23% with EDS-placebo) LS mean change from baseline: EDS-placebo=–0.42, XHANCE 372 mcg BID=–0.84

Treatment with XHANCE helped improve all 4 defining symptoms of nasal polyps.

90.6% of patients reported previous use of a topical steroid nasal spray for the treatment of nasal polyps, and 53.6% reported previous sinus surgery or polypectomy.1

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

XHANCE trial design & details

XHANCE is a corticosteroid indicated for the treatment of nasal polyps in patients 18 years of age or older.

XHANCE has been extensively studied in over 1500 patients.1-5

646 patients with bilateral nasal polyps evaluated for efficacy and safety for up to 24 weeks2,3

  • NAVIGATE I and NAVIGATE II were double-blind, placebo-controlled trials lasting 16 weeks with an 8-week open-label extension in patients with bilateral nasal polyps and moderate to severe congestion. All patients received XHANCE 372 mcg BID during the open-label extension1-3

928 patients with chronic sinusitis with and without nasal polyps in 2 open-label trials evaluated for safety for up to 12 months1,4

  • EXHANCE-3 and EXHANCE-12 were open-label studies lasting 3 months (n=705) and 12 months (n=223)1,4
 
   
 

NAVIGATE I and NAVIGATE II: Phase 3 trials evaluating efficacy and safety

Two similar randomized, placebo-controlled, multicenter studies to assess XHANCE safety and efficacy (n=646)1

Flow chart showing the study design and clinical trial format for NAVIGATE I and NAVIGATE II Flow chart showing the study design and clinical trial format for NAVIGATE I and NAVIGATE II

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 include2,3:

  • Change from baseline in sense of smell, rhinorrhea, and facial pain or pressure
  • 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

Details2,3,5:

  • The comparator used in the pivotal clinical studies was a liquid placebo delivered with an Optinose Exhalation Delivery System (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

EXHANCE-3 and EXHANCE-12: Phase 3 open-label studies

Data demonstrating safety for up to 1 year were also evaluated in 2 open-label studies in 928 patients with chronic sinusitis (CS) with or without nasal polyps.1,4*

Graphic showing EXHANCE-3 and EXHANCE-12 study design Graphic showing EXHANCE-3 and EXHANCE-12 study design

Key inclusion criteria4:

  • CS with or without nasal polyps*
  • Experiencing ≥2 defining symptoms of CS

*XHANCE is not indicated to treat CS.

References:
  1. Full Prescribing Information for XHANCE (fluticasone propionate). OptiNose US, Inc.; 2023.
  2. Leopold DA, Elkayam D, Messina JC, et al. NAVIGATE II: randomized, double-blind trial of the exhalation delivery system with fluticasone (EDS-FLU) for nasal polyposis. J Allergy Clin Immunol. 2019;143(1):126-134.
  3. Sindwani R, Han JK, Soteres DF, et al. NAVIGATE I: randomized, placebo-controlled, double-blind trial of the Exhalation Delivery System with fluticasone for chronic rhinosinusitis with nasal polyps. Am J Rhinol Allergy. 2019;33(1):69-82.
  4. Palmer JN, Jacobson KW, Messina JC, et al. EXHANCE-12: 1-year study of the exhalation delivery system with fluticasone (EDS-FLU) in chronic rhinosinusitis. Int Forum Allergy Rhinol. 2018;8(8):869-876.
  5. Data on file. OptiNose US, Inc.

Polyp Elimination (Grade=0) in at Least One Nostril2 — Secondary Endpoint

Graphic of polyp elimination percentage of patients in NAVIGATE II Week 16 double-blind period: EDS-placebo Group=4, XHANCE 186 mcg BID=9, XHANCE 372 mcg BID=14; in NAVIGATE II Week 24 open-label extension all patients receive XHANCE 372 mcg BID: XHANCE 372 mcg BID=28; XHANCE 372 mcg BID treatment group(2): 28% of patients achieved polyp elimination (grade=0) in at least one nostril at Week 24Graphic of polyp elimination percentage of patients in NAVIGATE II Week 16 double-blind period: EDS-placebo Group=4, XHANCE 186 mcg BID=9, XHANCE 372 mcg BID=14; in NAVIGATE II Week 24 open-label extension all patients receive XHANCE 372 mcg BID
XHANCE 372 mcg BID=28; XHANCE 372 mcg BID treatment group(2): 28% of patients achieved polyp elimination (grade=0) in at least one nostril at Week 24

 

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.

 

XHANCE trial design & details

XHANCE is a corticosteroid indicated for the treatment of nasal polyps in patients 18 years of age or older.

XHANCE has been extensively studied in over 1500 patients.1-5

646 patients with bilateral nasal polyps evaluated for efficacy and safety for up to 24 weeks2,3

  • NAVIGATE I and NAVIGATE II were double-blind, placebo-controlled trials lasting 16 weeks with an 8-week open-label extension in patients with bilateral nasal polyps and moderate to severe congestion. All patients received XHANCE 372 mcg BID during the open-label extension1-3

928 patients with chronic sinusitis with and without nasal polyps in 2 open-label trials evaluated for safety for up to 12 months1,4

  • EXHANCE-3 and EXHANCE-12 were open-label studies lasting 3 months (n=705) and 12 months (n=223)1,4
 
   
 

NAVIGATE I and NAVIGATE II: Phase 3 trials evaluating efficacy and safety

Two similar randomized, placebo-controlled, multicenter studies to assess XHANCE safety and efficacy (n=646)1

Flow chart showing the study design and clinical trial format for NAVIGATE I and NAVIGATE II Flow chart showing the study design and clinical trial format for NAVIGATE I and NAVIGATE II

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 include2,3:

  • Change from baseline in sense of smell, rhinorrhea, and facial pain or pressure
  • 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

Details2,3,5:

  • The comparator used in the pivotal clinical studies was a liquid placebo delivered with an Optinose Exhalation Delivery System (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

EXHANCE-3 and EXHANCE-12: Phase 3 open-label studies

Data demonstrating safety for up to 1 year were also evaluated in 2 open-label studies in 928 patients with chronic sinusitis (CS) with or without nasal polyps.1,4*

Graphic showing EXHANCE-3 and EXHANCE-12 study design Graphic showing EXHANCE-3 and EXHANCE-12 study design

Key inclusion criteria4:

  • CS with or without nasal polyps*
  • Experiencing ≥2 defining symptoms of CS

*XHANCE is not indicated to treat CS.

References:
  1. Full Prescribing Information for XHANCE (fluticasone propionate). OptiNose US, Inc.; 2023.
  2. Leopold DA, Elkayam D, Messina JC, et al. NAVIGATE II: randomized, double-blind trial of the exhalation delivery system with fluticasone (EDS-FLU) for nasal polyposis. J Allergy Clin Immunol. 2019;143(1):126-134.
  3. Sindwani R, Han JK, Soteres DF, et al. NAVIGATE I: randomized, placebo-controlled, double-blind trial of the Exhalation Delivery System with fluticasone for chronic rhinosinusitis with nasal polyps. Am J Rhinol Allergy. 2019;33(1):69-82.
  4. Palmer JN, Jacobson KW, Messina JC, et al. EXHANCE-12: 1-year study of the exhalation delivery system with fluticasone (EDS-FLU) in chronic rhinosinusitis. Int Forum Allergy Rhinol. 2018;8(8):869-876.
  5. Data on file. OptiNose US, Inc.

icon representing Iquality of life as measured by SNOT-22

Secondary endpoint:

Improvement in quality of life as measured by SNOT-222

Improvement in SNOT-22 scores2

Graphic of post hoc analysis of NAVIGATE I and II (n=218) SNOT-22 improvements EDS-placebo 12 points; XHANCE 21 pointsGraphic of post hoc analysis of NAVIGATE I and II (n=218) SNOT-22 improvements EDS-placebo 12 points; XHANCE 21 points

EDS-placebo (n=79), XHANCE 186 mcg (n=80), XHANCE 372 mcg BID (n=82).

  • Mean SNOT-22 scores improved by 21 points at Week 16 in patients taking XHANCE (both the 186 mcg BID dose and the 372 mcg BID dose)2
  • Minimal clinically important difference (MCID) of –9 is considered a clinically relevant improvement6,7
  • In the clinical trials for XHANCE, the mean baseline SNOT-22 score for all arms was ~502,3

 

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

 

Post hoc subgroup analysis

Improvement in SNOT-22 in patients with or without prior sinus surgery

Reduction in SNOT-22 score at Week 16 in the subgroups of patients with or without prior sinus surgery1

  • A post hoc analysis of a pooled population from NAVIGATE I and NAVIGATE II analyzed improvement in SNOT-22 score in the subgroup of patients who had sinus surgery and those without sinus surgery prior to study entry1
  • Patients were excluded from the studies if they had a history of sinus or nasal surgery within 6 months before screening2,3

  The following results are descriptive and should be interpreted with caution.

Post hoc analysis of NAVIGATE I and II
Pooled subgroup data (n=481)

with prior sinus surgery without prior sinus surgery with and without prior sinus surgery

 

Baseline grade: EDS-placebo, 3.7; XHANCE 186 mcg BID, 3.8; XHANCE 372 mcg BID, 3.7.1-3

IMPORTANT SAFETY INFORMATION
WARNINGS AND PRECAUTIONS:
  • Local Nasal Effects: epistaxis, erosion, ulceration, septal perforation, Candida albicans infection, and impaired wound healing. Monitor patients periodically for signs of possible changes on the nasal mucosa. Avoid use in patients with recent nasal ulcerations, nasal surgery, or nasal trauma until healing has occurred.

Please see additional Important Safety Information and full Prescribing Information, including Instructions for Use.

References:
  1. Data on file. OptiNose US, Inc.
  2. Leopold DA, Elkayam D, Messina JC, et al. NAVIGATE II: randomized double-blind trial of the exhalation delivery system with fluticasone (EDS-FLU) for nasal polyposis. J Allergy Clin Immunol. 2019;143(1):126-134.
  3. Sindwani R, Han JK, Soteres DF, et al. NAVIGATE I: randomized, placebo-controlled, double-blind trial of the Exhalation Delivery System with fluticasone for chronic rhinosinusitis with nasal polyps. Am J Rhinol Allergy. 2019;33(1):69-82.
 

Post hoc subgroup analysis

Improvement in SNOT-22 in patients previously
using standard nasal steroids1

Improvements in SNOT-22 scores in the subgroup of patients reporting use of standard nasal steroids prior to study entry1

  • Mean SNOT-22 scores improved by 21 points at Week 16 in patients taking XHANCE (both the 186 mcg BID dose and the 372 mcg BID dose)1
  • Minimal clinically important difference (MCID) of –9 is considered a clinically relevant improvement2,3
  • In the clinical trials for XHANCE, the mean baseline SNOT-22 score for all arms was ~501,4,5
  • In a subgroup of patients reporting use of a standard nasal steroid within 30 days of the screening visit1:

    – Patients reported a mean treatment duration of 3 years with a standard nasal steroid

    •   The results shown below are descriptive and should be interpreted with caution.

    Post hoc analysis of NAVIGATE I and II
    Pooled subgroup data (n=218)

    LS Mean Change LS Mean Change

    SNOT-22 is a questionnaire for assessing symptoms, quality of life, and functioning. Patients report answers to 22 questions using a scale from 0 (“no problem”) to 5 (“problem as bad as can be”). Responses are summed, and total score ranges from 0 to 110, with a mean score of 9.3 for healthy patients.

    IMPORTANT SAFETY INFORMATION
    WARNINGS AND PRECAUTIONS:
    • Local Nasal Effects: epistaxis, erosion, ulceration, septal perforation, Candida albicans infection, and impaired wound healing. Monitor patients periodically for signs of possible changes on the nasal mucosa. Avoid use in patients with recent nasal ulcerations, nasal surgery, or nasal trauma until healing has occurred.

    Please see additional Important Safety Information and full Prescribing Information, including Instructions for Use.

    References:
    1. Senior BA, Schlosser RJ, Bosso J, Soler ZM. Efficacy of the exhalation delivery system with fluticasone in patients who remain symptomatic on standard nasal steroid sprays. Int Forum Allergy Rhinol. 2021;11(5):837-845.
    2. Hopkins C, Gillett S, Slack R, Lund VJ, Browne JP. Psychometric validity of the 22-item Sinonasal Outcome Test. Clin Otolaryngol. 2009;34(5):447-454.
    3. Le PT, Soler ZM, Jones R, Mattos JL, Nguyen SA, Schlosser RJ. Systematic review and meta-analysis of SNOT-22 outcomes after surgery for chronic rhinosinusitis with nasal polyposis. Otolaryngol Head Neck Surg. 2018;159(3):414-423.
    4. Leopold DA, Elkayam D, Messina JC, Kosik-Gonzalez C, Djupesland PG, Mahmoud RA. NAVIGATE II: randomized double-blind trial of the exhalation delivery system with fluticasone(EDS-FLU) for nasal polyposis. J Allergy Clin Immunol. 2019;143(1):126-134.
    5. Sindwani R, Han JK, Soteres DF, et al. NAVIGATE I: randomized, placebo-controlled, double-blind trial of the exhalation delivery system with fluticasone for chronic rhinosinusitis with nasal polyps. Am J Rhinol Allergy. 2019;33(1):69-82.
     

    XHANCE trial design & details

    XHANCE is a corticosteroid indicated for the treatment of nasal polyps in patients 18 years of age or older.

    XHANCE has been extensively studied in over 1500 patients.1-5

    646 patients with bilateral nasal polyps evaluated for efficacy and safety for up to 24 weeks2,3

    • NAVIGATE I and NAVIGATE II were double-blind, placebo-controlled trials lasting 16 weeks with an 8-week open-label extension in patients with bilateral nasal polyps and moderate to severe congestion. All patients received XHANCE 372 mcg BID during the open-label extension1-3

    928 patients with chronic sinusitis with and without nasal polyps in 2 open-label trials evaluated for safety for up to 12 months1,4

    • EXHANCE-3 and EXHANCE-12 were open-label studies lasting 3 months (n=705) and 12 months (n=223)1,4
     
       
     

    NAVIGATE I and NAVIGATE II: Phase 3 trials evaluating efficacy and safety

    Two similar randomized, placebo-controlled, multicenter studies to assess XHANCE safety and efficacy (n=646)1

    Flow chart showing the study design and clinical trial format for NAVIGATE I and NAVIGATE II Flow chart showing the study design and clinical trial format for NAVIGATE I and NAVIGATE II

    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 include2,3:

    • Change from baseline in sense of smell, rhinorrhea, and facial pain or pressure
    • 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

    Details2,3,5:

    • The comparator used in the pivotal clinical studies was a liquid placebo delivered with an Optinose Exhalation Delivery System (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

    EXHANCE-3 and EXHANCE-12: Phase 3 open-label studies

    Data demonstrating safety for up to 1 year were also evaluated in 2 open-label studies in 928 patients with chronic sinusitis (CS) with or without nasal polyps.1,4*

    Graphic showing EXHANCE-3 and EXHANCE-12 study design Graphic showing EXHANCE-3 and EXHANCE-12 study design

    Key inclusion criteria4:

    • CS with or without nasal polyps*
    • Experiencing ≥2 defining symptoms of CS

    *XHANCE is not indicated to treat CS.

    References:
    1. Full Prescribing Information for XHANCE (fluticasone propionate). OptiNose US, Inc.; 2023.
    2. Leopold DA, Elkayam D, Messina JC, et al. NAVIGATE II: randomized, double-blind trial of the exhalation delivery system with fluticasone (EDS-FLU) for nasal polyposis. J Allergy Clin Immunol. 2019;143(1):126-134.
    3. Sindwani R, Han JK, Soteres DF, et al. NAVIGATE I: randomized, placebo-controlled, double-blind trial of the Exhalation Delivery System with fluticasone for chronic rhinosinusitis with nasal polyps. Am J Rhinol Allergy. 2019;33(1):69-82.
    4. Palmer JN, Jacobson KW, Messina JC, et al. EXHANCE-12: 1-year study of the exhalation delivery system with fluticasone (EDS-FLU) in chronic rhinosinusitis. Int Forum Allergy Rhinol. 2018;8(8):869-876.
    5. Data on file. OptiNose US, Inc.

    Patient Global Impression of Change (PGIC) at Week 162

    Secondary endpoint:

    Graphic of percentage of patients reporting Patient Global Impression of Change (PGIC) of “much improved” or “very much improved” symptoms from baseline: EDS-placebo (n=79) 32, XHANCE 186 mcg BID (n=80) 68, XHANCE 372 mcg BID (n=82) 68Graphic of percentage of patients reporting Patient Global Impression of Change (PGIC) of “much improved” or “very much improved” symptoms from baseline: EDS-placebo (n=79) 32, XHANCE 186 mcg BID (n=80) 68, XHANCE 372 mcg BID (n=82) 68

    ~68% of patients reported a Patient Global Impression of Change (PGIC) of “much improved” or “very much improved”2

    PGIC is a commonly used method of assessing clinically important change. With PGIC, the qualitative assessment of meaningful change is determined by the patient using a 7-item scale ranging from “very much worse” to “very much improved.”

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

     

    XHANCE trial design & details

    XHANCE is a corticosteroid indicated for the treatment of nasal polyps in patients 18 years of age or older.

    XHANCE has been extensively studied in over 1500 patients.1-5

    646 patients with bilateral nasal polyps evaluated for efficacy and safety for up to 24 weeks2,3

    • NAVIGATE I and NAVIGATE II were double-blind, placebo-controlled trials lasting 16 weeks with an 8-week open-label extension in patients with bilateral nasal polyps and moderate to severe congestion. All patients received XHANCE 372 mcg BID during the open-label extension1-3

    928 patients with chronic sinusitis with and without nasal polyps in 2 open-label trials evaluated for safety for up to 12 months1,4

    • EXHANCE-3 and EXHANCE-12 were open-label studies lasting 3 months (n=705) and 12 months (n=223)1,4
     
       
     

    NAVIGATE I and NAVIGATE II: Phase 3 trials evaluating efficacy and safety

    Two similar randomized, placebo-controlled, multicenter studies to assess XHANCE safety and efficacy (n=646)1

    Flow chart showing the study design and clinical trial format for NAVIGATE I and NAVIGATE II Flow chart showing the study design and clinical trial format for NAVIGATE I and NAVIGATE II

    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 include2,3:

    • Change from baseline in sense of smell, rhinorrhea, and facial pain or pressure
    • 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

    Details2,3,5:

    • The comparator used in the pivotal clinical studies was a liquid placebo delivered with an Optinose Exhalation Delivery System (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

    EXHANCE-3 and EXHANCE-12: Phase 3 open-label studies

    Data demonstrating safety for up to 1 year were also evaluated in 2 open-label studies in 928 patients with chronic sinusitis (CS) with or without nasal polyps.1,4*

    Graphic showing EXHANCE-3 and EXHANCE-12 study design Graphic showing EXHANCE-3 and EXHANCE-12 study design

    Key inclusion criteria4:

    • CS with or without nasal polyps*
    • Experiencing ≥2 defining symptoms of CS

    *XHANCE is not indicated to treat CS.

    References:
    1. Full Prescribing Information for XHANCE (fluticasone propionate). OptiNose US, Inc.; 2023.
    2. Leopold DA, Elkayam D, Messina JC, et al. NAVIGATE II: randomized, double-blind trial of the exhalation delivery system with fluticasone (EDS-FLU) for nasal polyposis. J Allergy Clin Immunol. 2019;143(1):126-134.
    3. Sindwani R, Han JK, Soteres DF, et al. NAVIGATE I: randomized, placebo-controlled, double-blind trial of the Exhalation Delivery System with fluticasone for chronic rhinosinusitis with nasal polyps. Am J Rhinol Allergy. 2019;33(1):69-82.
    4. Palmer JN, Jacobson KW, Messina JC, et al. EXHANCE-12: 1-year study of the exhalation delivery system with fluticasone (EDS-FLU) in chronic rhinosinusitis. Int Forum Allergy Rhinol. 2018;8(8):869-876.
    5. Data on file. OptiNose US, Inc.

    Image of NAVIGATE I in the American Journal of Rhinology and Allergy

    Review details of NAVIGATE I in the American Journal of Rhinology and Allergy.

    Image of NAVIGATE II in the American Journal of Rhinology and Allergy

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

     

    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.

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