Optinose Announces Additional Positive Results from ReOpen2 and Initial Results from Pooled Analyses of Both Trials in the ReOpen Program
Company previously announced positive top-line results from both ReOpen1 and ReOpen2, the landmark trials evaluating XHANCE as a treatment for chronic sinusitis
Multiple secondary endpoints from ReOpen2 indicate patients treated with XHANCE experienced improvement in symptoms and quality of life when compared to patients treated with placebo
In pooled data from ReOpen1 and ReOpen2, XHANCE demonstrated a benefit relative to placebo on CT scans in patients with chronic sinusitis without nasal polyps
As previously disclosed, both co-primary endpoints in ReOpen2 showed significant improvement among patients treated with XHANCE versus placebo comparator, including combined symptom score at 4 weeks and average of percentages of opacified volume (APOV) at 24 weeks. In pre-planned, exploratory, secondary analyses of ReOpen2, patients treated with XHANCE were also found to have larger improvements than patients receiving placebo comparator at the 4-week time point on each of the four individual defining symptoms of chronic rhinosinusitis, including congestion/obstruction, rhinorrhea (thick drainage), facial pain or pressure, and loss of sense of smell. Pre-planned secondary analyses also revealed greater improvement on the sinonasal outcomes test (22 item), a commonly used measure of symptoms, quality of life, and functioning in chronic rhinosinusitis, at week 24 for patients receiving XHANCE then placebo comparator. Nominal p-values for the differences between the group of patients receiving XHANCE and the group of patients receiving placebo were less than 0.05 on each of these measures.
Many people with chronic rhinosinusitis have tried and are frustrated with standard nasal steroid sprays. To inform possible differences in response of patients previously using a standard nasal steroid spray, a pre-planned analysis of pooled data from ReOpen1 and ReOpen2 assessed symptom improvement for patients entering the trials with at least moderate symptoms despite reporting use of a standard nasal steroid spray. For this subgroup, patients receiving XHANCE improved more from baseline than patients receiving placebo comparator. Additionally, a pooled analysis was performed to assess change in CT scans, measured by APOV at week 24, for the subgroup of patients receiving XHANCE who had chronic sinusitis without nasal polyps. Compared to patients treated with placebo comparator, XHANCE treatment produced greater reduction in sinus opacification in this subgroup (-6.31% vs -1.55%, nominal p-value of 0.004). Differences between active and placebo in the groups receiving one or two sprays per nostril twice daily were similar and nominally statistically significant.
“We are pleased to see new evidence from ReOpen2 suggesting XHANCE treatment produces benefits on each of the cardinal symptoms of chronic rhinosinusitis and on a measure of quality of life. Symptom relief and quality of life represent the main treatment goals for patients with chronic rhinosinusitis and their doctors,” said
The safety profile and tolerability of XHANCE in these trials were consistent with its currently labelled safety profile. In pooled data from both trials inclusive of both dose groups, adverse events occurring at a rate of more than 3% in patients receiving XHANCE that were also more common than in the group receiving the EDS-placebo were epistaxis, COVID-19, nasopharyngitis, and headache.
Summary of Efficacy Results
|Difference from Placebo EDS|
|Treatment||n||Baseline Score||LS Mean Change
|Change in SNOT-22 from Baseline to Week 24 (ReOpen2)|
|XHANCE 186 or 372 mcg||145||48.57||-17.49||-8.77||0.001|
|Change in Symptoms in Prior Nasal Steroid Users from Baseline to Week 4 (Pooled)|
|XHANCE 186 or 372 mcg||172||5.63||-1.46||-0.70||<0.001|
|Change in APOV in CS Patients without Nasal Polyps from Baseline to Week 24 (Pooled)|
|XHANCE 186 or 372 mcg||225||61.33||-6.31||-4.76||0.004|
|XHANCE 372 mcg||112||61.26||-6.50||-4.95||0.010|
|XHANCE 186 mcg||113||61.40||-6.12||-4.57||0.019|
Summary of Safety Results
|Summary of Adverse Events with XHANCE Reported in ≥ 3%
and More Common Than Placebo EDS in Pooled data
|Adverse Event (AE)||Placebo EDS BID
|XHANCE 186 mcg BID
|XHANCE 372 mcg BID
|Epistaxis||1 (0.5)||9 (4.9)||20 (10.9)|
|COVID-19||8 (4.3)||5 (2.7)||12 (6.7)|
|Nasopharyngitis||8 (4.3)||9 (4.9)||7 (3.8)|
|Headache||7 (3.7)||4 (2.2)||10 (5.5)|
The global, randomized, double-blind, placebo-controlled Phase 3 ReOpen1 trial evaluated the efficacy and safety of intranasal administration of 186 and 372 mcg twice daily of OPN-375, marketed as XHANCE, in patients with chronic sinusitis (CS) with or without nasal polyps over 24 weeks. The co-primary efficacy endpoints were the change from baseline in symptoms as measured by a composite score of nasal congestion, facial pain or pressure sensation, and nasal discharge at the end of week 4, and the change from baseline to week 24 in the average of the percentages of ethmoid and maxillary sinus volume occupied by disease as measured by CT scan.
The global, randomized, double-blind, placebo-controlled Phase 3 ReOpen2 trial evaluated the efficacy and safety of one and two sprays of XHANCE (OPN-375) in each nostril twice daily, over 24 weeks in patients with chronic sinusitis (CS) who did not have nasal polyps. The co-primary endpoints were change from baseline in symptoms, as measured by a composite score of patient-reported symptoms (including nasal congestion, facial pain or pressure sensation, and nasal discharge) at the end of week 4, and objective change in inflammation inside the sinus cavities, as measured by the change in average of percentages of volume occupied by disease across the ethmoid and maxillary sinuses as measured by CT scan. The ReOpen trial program is a landmark research program because these are the first ever large, controlled trials we are aware of that show significant improvement of both symptoms and inflammation inside the sinuses with a nasal therapy.
About Chronic Sinusitis
Chronic sinusitis (CS), cited as the second most common chronic disease of adults in the US, is a serious chronic inflammatory disease that may affect as many as 30 million adults in
XHANCE is a drug-device combination product that uses the Exhalation Delivery System (also referred to as the EDS) designed to deliver a topical anti-inflammatory to the high and deep regions of the nasal cavity where sinuses ventilate and drain. XHANCE is approved by
Important Safety Information
CONTRAINDICATIONS: Hypersensitivity to any ingredient in XHANCE.
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.
- Close monitoring for glaucoma and cataracts is warranted.
- Hypersensitivity reactions (e.g., anaphylaxis, angioedema, urticaria, contact dermatitis, rash, hypotension, and bronchospasm) have been reported after administration of fluticasone propionate. Discontinue XHANCE if such reactions occur.
- Immunosuppression: potential increased susceptibility to or worsening of infections (e.g., existing tuberculosis; fungal, bacterial, viral, or parasitic infection; ocular herpes simplex). Use with caution in patients with these infections. More serious or even fatal course of chickenpox or measles can occur in susceptible patients.
- Hypercorticism and adrenal suppression may occur with very high dosages or at the regular dosage in susceptible individuals. If such changes occur, discontinue XHANCE slowly.
- Patients with major risk factors for decreased bone mineral content should be monitored and treated with established standards of care.
ADVERSE REACTIONS: The most common adverse reactions (incidence ≥ 3%) are epistaxis, nasal septal ulceration, nasopharyngitis, nasal mucosal erythema, nasal mucosal ulcerations, nasal congestion, acute sinusitis, nasal septal erythema, headache, and pharyngitis.
DRUG INTERACTIONS: Strong cytochrome P450 3A4 inhibitors (e.g., ritonavir, ketoconazole): Use not recommended. May increase risk of systemic corticosteroid effects.
USE IN SPECIFIC POPULATIONS: Hepatic impairment. Monitor patients for signs of increased drug exposure.
Please see full Prescribing Information.
Cautionary Note on Forward-Looking Statements
This press release contains forward-looking statements within the meaning of the
Optinose Investor/Media Contact
Source: Optinose, Inc.