XHANCE significantly reduced both symptoms and sinus opacification in participants with chronic sinusitis (chronic rhinosinusitis) in two randomized controlled Phase 3 Clinical Trials (ReOpen1 and ReOpen2)
FDA Supplemental New Drug Application Filed with Prescription Drug User Fee Act Target Goal Date of March 16, 2024
YARDLEY, Pa., Jan. 18, 2024 (GLOBE NEWSWIRE) -- Optinose (NASDAQ:OPTN), a pharmaceutical company focused on patients treated by ear, nose and throat (ENT) and allergy specialists, today announced peer-reviewed publication of results from both ReOpen1 and ReOpen2 in the Journal of Allergy and Clinical Immunology: In Practice1.
The ReOpen program evaluated XHANCE for treatment of adults with chronic sinusitis (chronic rhinosinusitis). A drug-device combination product, XHANCE® (fluticasone propionate) nasal spray uniquely combines a widely used nasal anti-inflammatory drug with the Exhalation Delivery System, an innovative delivery system designed to deliver the medication high and deep into difficult-to-access sinuses and sinonasal drainage tracts.
"Patients with chronic sinusitis often suffer for years and may use multiple over-the-counter treatments in a search for ways to alleviate their symptoms. The burden of chronic sinusitis has been measured and is serious, with a degree of impaired quality of life and functioning comparable to other serious chronic conditions such as chronic heart failure, sciatica, or migraine. Chronic sinusitis is also common: data suggests it is one of the top diagnoses in adult outpatient physician visits. Although surgery is available, there has never been a medication approved by the FDA as safe and effective for this disease," said Ramy Mahmoud, MD, MPH, CEO of Optinose. "Having a proven effective medication would finally allow doctors to have confidence that they can offer some relief to tens of millions of people suffering from this burdensome inflammatory condition."
As detailed in the new scientific publication Efficacy of EDS-FLU for Chronic Rhinosinusitis: Two Randomized Controlled Trials (ReOpen1 and ReOpen2), both trials showed statistically significant improvement in symptoms, and in inflammation inside the sinuses, in patients with chronic sinusitis (chronic rhinosinusitis) treated with XHANCE compared to patients receiving a vehicle combined with the Exhalation Delivery System (EDS-placebo). The primary endpoints include a composite symptom score (congestion, facial pain or pressure, and nasal discharge) and CT scans of the sinuses to objectively measure change in inflammation inside the sinus cavities. In additional statistically well-controlled measures, these trials also showed that XHANCE reduced the incidence of acute disease exacerbations by more than half and that treatment significantly reduced symptoms even for patients who entered the trials with symptoms despite using a standard-delivery nasal spray steroid, which are now generally available at prescription strength as over-the-counter treatments.
The safety profile and tolerability of XHANCE for patients in the ReOpen trials was generally consistent with its currently labeled safety profile. The most common adverse reactions (incidence = 3%) in the ReOpen program were epistaxis, headache, and nasopharyngitis.
"With the help of patients and doctors in many countries, after years of effort, we are thrilled to see that results from these two pivotal trials are now available in a peer reviewed publication. Not only do these data support the sNDA we filed with FDA in 2023," stated John Messina, PharmD, Senior Vice President of Clinical Research and Medical Affairs, "but they represent the first body of large, controlled trial evidence we are aware of showing that any nasal medication can produce improvement in symptoms and can reduce inflammation inside the sinus cavities of patients suffering from chronic sinusitis either with or without concurrent nasal polyps. Our team is proud of this breakthrough in the treatment of chronic sinusitis, and we sincerely thank the healthcare professionals who advised us along the way as well as those at our research sites and all the patients whose participation made this program possible."
About the ReOpen Program
The ReOpen program comprised two global, randomized, double-blind, placebo-controlled Phase 3 trials that evaluated the efficacy and safety of one or two sprays of XHANCE in each nostril twice daily, over 24 weeks, in patients suffering from chronic sinusitis. In ReOpen1, the first of the two trials, 332 chronic sinusitis patients either with or without concurrent nasal polyps were treated. In ReOpen2, 222 chronic sinusitis patients who did not have polyps in the nasal cavity were treated. The co-primary endpoints were change from baseline in symptoms, as measured by composite symptom score (nasal congestion, facial pain or pressure, and nasal discharge) at the end of week 4, and change in inflammation inside the sinus cavities, as measured by CT scans (change in the average of the percentages of volume occupied by disease in the ethmoid and maxillary sinuses) at week 24. The ReOpen trial program is a landmark research program that included the first ever large, controlled trials we are aware of to demonstrate that any nasal medication produces significant improvement in both symptoms and inflammation inside the sinuses for patients with chronic sinusitis, regardless of whether or not nasal polyps are present, and to demonstrate significant reduction in the number of acute exacerbations.
About Chronic Sinusitis
Chronic sinusitis (CS), also called "chronic rhinosinusitis", has been cited as the second most common chronic disease of adults in the U.S.2 It is a serious chronic inflammatory disease affecting as many as 30 million adults in the U.S. and burdens the U.S. economy with over $30 billion in direct and indirect costs every year.3 CS is characterized by chronic inflammation affecting the paranasal sinuses and the nasal cavity, where the openings from the sinuses normally ventilate and drain. Chronic sinusitis is associated with symptoms that persist for at least 12 weeks, with many patients suffering for years. In addition, the condition is often associated with multiple acute exacerbations that require medical care and result in substantial use of antibiotics. In some patients, chronic sino-nasal inflammation is accompanied by development of polyps in the nasal cavities, referred to as nasal polyposis. Today, there are no FDA-approved drug treatments for the majority of chronic sinusitis patients, those who do not have polyps in the nasal cavity, although there are medications, including XHANCE, that have been approved by FDA for treatment of the smaller population of chronic rhinosinusitis patients who also have nasal polyps. The term "chronic rhinosinusitis" is sometimes used instead of "chronic sinusitis" to acknowledge that inflammation inside the sinuses is typically accompanied by inflammation in the nasal cavity.
About Optinose
Optinose is a global specialty pharmaceutical company focused on serving the needs of patients cared for by ear, nose and throat (ENT) and allergy specialists. To learn more, please visit www.optinose.com or follow us on X and LinkedIn.
About XHANCE
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 the U.S. Food and Drug Administration for the treatment of chronic rhinosinusitis with nasal polyps in patients 18 years of age or older and has been studied for treatment of chronic sinusitis (notably including patients without polyps in the nasal cavity) in two phase 3 trials, ReOpen1 and ReOpen2. These trials are the first ever that we are aware of that show improvement in both symptoms and inflammation inside the sinuses, and reduction in acute exacerbations of disease, with a nasal therapy for chronic sinusitis patients, including patients with or without nasal polyps. If approved, XHANCE may be the first drug ever FDA-approved for treatment of chronic rhinosinusitis either with or without nasal polyps.
Important Safety Information
CONTRAINDICATIONS: Hypersensitivity to any ingredient in XHANCE.
WARNINGS AND PRECAUTIONS:
- Local Nasal Adverse Reactions: 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.
- 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 and Risk of Infection: 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, including Instructions for Use
References
- James N. Palmer, Nithin D. Adappa, Rakesh K. Chandra, Greg E. Davis, Mahboobeh Mahdavinia, John Messina, Randall A. Ow, Zara M. Patel, Anju T. Peters, Harry Sacks, Rodney J. Schlosser, Raj Sindwani, Zachary M. Soler, Andrew A. White, Sarah K. Wise, Ramy A. Mahmoud, Efficacy of EDS-FLU for Chronic Rhinosinusitis: Two Randomized Controlled Trials (ReOpen1 and ReOpen2), The Journal of Allergy and Clinical Immunology: In Practice, 2024" ISSN 2213-2198, https://doi.org/10.1016/j.jaip.2023.12.016. (https://www.sciencedirect.com/science/article/pii/S221321982301365X)
- Hamilos DL. Chronic rhinosinusitis: epidemiology and medical management. J Allergy Clin Immunol. 2011 Oct;128(4):693-707; quiz 708-9. doi: 10.1016/j.jaci.2011.08.004. Epub 2011 Sep 3. PMID: 21890184.
- Palmer JN, Messina JC, Biletch R, Grosel K, Mahmoud RA. A cross-sectional, population-based survey of U.S. adults with symptoms of chronic rhinosinusitis. Allergy Asthma Proc. 2019 Jan 14;40(1):48-56. doi: 10.2500/aap.2019.40.4182. PMID: 30582496.
Cautionary Note on Forward-Looking Statements
This press release contains forward-looking statements within the meaning of the U.S. Private Securities Litigation Reform Act of 1995. All statements that are not historical facts are hereby identified as forward-looking statements for this purpose and include, among others, statements relating to the potential for XHANCE to be the first FDA approved drug product for chronic rhinosinusitis and the potential benefits of such label expansion; and other statements regarding the Company's future operations, prospects, objectives, and other future events. Forward-looking statements are based upon management's current expectations and assumptions and are subject to a number of risks, uncertainties and other factors that could cause actual results and events to differ materially and adversely from those indicated by such forward-looking statements including, among others: physician and patient acceptance of XHANCE for its current and any potential future indication; potential for varying interpretation of clinical trial results of XHANCE for the treatment of chronic rhinosinusitis; potential that the FDA does not meet the PDUFA target goal date; risks and uncertainties relating to FDA approval of XHANCE for the treatment of chronic rhinosinusitis; the prevalence of chronic sinusitis and market opportunities for XHANCE may be smaller than the Company expects; and the risks, uncertainties and other factors discussed under the caption "Item 1A. Risk Factors" and elsewhere in our most recent Form 10-K and Form 10-Q filings with the Securities and Exchange Commission - which are available at www.sec.gov. As a result, you are cautioned not to place undue reliance on any forward-looking statements. Any forward-looking statements made in this press release speak only as of the date of this press release, and we undertake no obligation to update such forward-looking statements, whether as a result of new information, future developments or otherwise.
Optinose Investor Contact
Jonathan Neely
jonathan.neely@optinose.com
267.521.0531
