Study: LYR-210 Shows Promise in Chronic Rhinosinusitis with Nasal Polyps

New study findings from Lyra Therapeutics, Inc. announced positive results from its ENLIGHTEN 2 phase 3 clinical trial, which evaluated LYR-210, an investigational product candidate for the treatment of chronic rhinosinusitis (CRS). The trial met its primary end point, demonstrating significant improvement in a composite of the 3 cardinal symptoms (3CS) of CRS—nasal obstruction, nasal discharge, and facial pain or pressure—at week 24, investigations provided in a news release.¹

Women feeling unwell and sinus on gray background - Image credit: eddows | stock.adobe.com

“The positive results seen in the ENLIGHTEN 2 study are impressive and represent what could be a promising new treatment approach for the many CRS patients that I see every day in my practice who are underserved by limited therapies,” Zachary Soler, MD, MSc, professor in the department of otolaryngology-head and neck surgery at the Medical University of South Carolina and coordinating lead investigator for the ENLIGHTEN 2 trial, said in a news release.¹

Causes, Signs, and Symptoms of CRS

CRS occurs when the lining of the sinuses swells due to inflammation, also known as chronic sinusitis. While the cause remains unknown, investigators believe CRS is triggered by the immune system overreacting to something in the sinuses, which persists for nearly 12 weeks. Symptoms include facial pain, post-nasal drip, and thick yellow or green mucus in the nose. In some cases, individuals could develop noncancerous growths in the nose and sinuses caused by the severe swelling. The condition can be treated by simply washing out the nose with saline daily or using a nasal steroid spray; however, further treatment options such as steroid pills can be used if symptoms reoccur.^2,3

LYR-210 could provide further treatment options for individuals with CRS who have failed other therapies. As an investigational product candidate and bioabsorbable nasal implant, LYR-210 is indicated to offer 6 months of continuous inflammatory therapy and mometasone furoate to the sinonasal passages following insertion in a simple, in-office procedure.¹

“We believe this has the potential to provide a path to advance LYR-210 to treat CRS, offering 6 months of therapy in a single administration for millions of patients who do not respond to standard CRS medical management,” Maria Palasis, PhD, president and CEO of Lyra Therapeutics, said in the news release.¹

Overview of the Enlighten Clinical Program

The ENLIGHTEN program consists of 2 phase 3 clinical trials, ENLIGHTEN 1 and ENLIGHTEN 2, both of which are designed to assess the effectiveness and safety of LYR-210 in treating CRS. While the ENLIGHTEN 2 trial successfully met its primary and key secondary end points, the ENLIGHTEN 1 trial did not achieve its primary or secondary end points, according to a May 2024 report.¹

A total of 180 individuals with CRS who had not responded to medical management and had not undergone previous ethmoid sinus surgery were enrolled in each ENLIGHTEN trial. Individuals were then randomly assigned to receive either LYR-210 (7500µg mometasone furoate) or a sham control. The study authors noted that the primary end points for both trials, assessed at 24 weeks, aimed to evaluate the long-acting therapeutic effect of LYR-210 in delivering continuous anti-inflammatory relief to the nasal passages for 6 months.¹

Positive Phase 3 Trial Results

The ENLIGHTEN 2 phase 3 clinical trial of LYR-210 for CRS met its primary end point with statistically significant improvement in the 3CS of CRS at week 24 among individuals without nasal polyps (P = 0.0078). Additionally, the results demonstrated statistically significant improvements in 3CS for the full patient population (P = 0.0209) and clinically meaningful, sustained improvements in SNOT-22 scores as early as week 4 (P = 0.0456), alongside numerical improvement in ethmoid sinus opacification on CT scans and fewer endoscopic sinus surgeries in the LYR-210 group compared to sham.¹

“The more than 20-point improvement from baseline in SNOT-22 score after LYR-210 treatment represents a clinically meaningful improvement in patient symptoms,” Soler said in the news release.¹

Additionally, a pooled analysis of 64 individuals with CRS that experienced grade 1 nasal polyps from the ENLIGHTEN 1 and ENLIGHTEN 2 trials indicated consistent positive trends for LYR-210 compared to sham over 24 weeks.¹

“Looking further ahead, we envision LYR-210 achieving its potential to benefit both non-polyp and polyp patients, positioning us to become a leader in CRS and validating our platform for future ENT indications,” Palasis concluded.¹

REFERENCES

1. Lyra Therapeutics Reports Positive Results from the ENLIGHTEN 2 Phase 3 Trial of LYR-210 Achieving Statistically Significant Results for Primary and Key Secondary Endpoints in the Treatment of Chronic Rhinosinusitis (CRS). Lyra Therapeutics. June 2, 2025. Accessed June 4, 2025. https://investors.lyratherapeutics.com/news-releases/news-release-details/lyra-therapeutics-reports-positive-results-enlighten-2-phase-3

2. Chronic Sinusitis. Cleveland Clinic. News release. Updated July 26, 2023. Accessed June 4, 2025. https://my.clevelandclinic.org/health/diseases/17700-chronic-sinusitis

3. Chronic Rhinosinusitis: What You Need to Know. American Family Physician. News release. 2017. Accessed June 4, 2025. https://www.aafp.org/pubs/afp/issues/2017/1015/p500-s1.html#:~:text=Chronic%20Rhinosinusitis:%20What%20You%20Need%20to%20Know,of%20the%20sinuses%20swells%20because%20of%20inflammation.&text=*%20Very%20rarely%2C%20it%20may%20be%20caused,vessels%2C%20cystic%20fibrosis%2C%20or%20primary%20ciliary%20dyskinesia.