Novel Resorbable Sinonasal Implant Significantly Reduces Symptoms in Treatment-Resistant CRS

An investigational bioresorbable sinonasal implant from Lyra Therapeutics achieved statistically significant improvement in chronic rhinosinusitis (CRS) symptoms in adults, meeting its primary endpoint in the ENLIGHTEN 2 phase 3 clinical trial, according to a company announcement.¹ Specifically, when compared to sham control in study participants without nasal polyps, LYR-210 demonstrated significant improvement in a composite of 3 cardinal symptoms (3CS) of CRS, nasal obstruction, nasal discharge, facial pain/pressure, at 24 weeks (-1.13; P =.008).

Nasal polyps cross section view

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The company also reported significant improvements in the key secondary endpoints of 3CS after 24 weeks of treatment in the full ENLIGTHEN 2 population (ie, participants with and with out nasal polyps) (-0.90; P = .021) and in scores on the sinonasal outcome test (SNOT-22) (-8.7; P =.010). Lyra reported symptom improvement as early as week 4 and that the safety profile of LYR-210 was similar to sham control, consistent with outcomes of previous studies.¹

LYR-210 represents a novel therapeutic approach for adults with CRS who have failed medical management and require further intervention. The bioabsorbable nasal implant delivers 7500 µg of mometasone furoate continuously over 6 months and is inserted during a simple, in-office procedure, according to the company statement.¹ The approach may help address the persistent symptoms experienced by the estimated 4 million individuals in the US with CRS who experience no relief annually, Lyra Pharmaceuticals said.¹ Overall, CRS affects approximately 14.6% of the US population.² Importantly, it is the fifth most common condition treated with antibiotics, according to the National Institutes of Health.²

“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 said.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,” added Soler who is also the coordinating lead investigator for the ENLIGHTEN 2 trial.¹

Final results from ENLIGHTEN 2 will be presented at the 71^st Annual Meeting of the American Rhinologic Society, October 2025, Lyra Pharmaceuticals stated.

The ENLIGHTEN 2 trial enrolled approximately 180 adults with CRS who were nonresponders to medical management and had not undergone prior ethmoid sinus surgery. Participants were randomly assigned 2:1 to receive either LYR-210 or sham control.

Beyond the primary endpoint success, investigators observed clinically meaningful improvements in quality of life measures, according to the statement. The improvements seen in SNOT-22 scores after just 4 weeks were sustained throughout the 24-week study. The treatment group achieved more than twice the minimal clinically important difference at week 24 compared to baseline (-22.4 points).¹

Objective radiologic evidence supported the clinical findings. Computed tomography scans showed numerical improvement in ethmoid sinus opacification in the LYR-210 group compared to the sham control group at week 20 (-2.15; P = .181). Participants in the LYR-210 group also required fewer endoscopic sinus surgeries compared to the control group, though both groups showed similar rates of corticosteroid rescue medication use.¹

Safety data demonstrated no product-related serious adverse events (AEs) in the ENLIGHTEN 2 trial. The most commonly reported AEs included epistaxis, upper respiratory tract infection, chronic sinusitis, acute sinusitis, nasopharyngitis, COVID-19, and headache.

The company also conducted a pooled analysis of 64 participants with CRS with grade 1 nasal polyps from both phase 3 ENLIGHTEN trials. This subset showed consistent positive trends across multiple endpoints, including 3CS improvement (-1.13; P = .084) and enhanced scores on SNOT-22 (-8.7; P =.133) at 24 weeks. According to the Lyra statement, benefits were observed as early as week 4.¹

The ENLIGHTEN program's mixed results suggest a complicated regulatory landscape. While ENLIGHTEN 2 achieved its primary and key secondary endpoints, the previously reported ENLIGHTEN 1 trial failed to meet its primary endpoint or secondary endpoints in May 2024.³ Despite this divergence, Lyra plans to pursue FDA alignment for an NDA submission in patients without nasal polyps based on the ENLIGHTEN 2 success.

For patients with nasal polyps, the company plans to continue development based on December 2024 FDA alignment regarding endpoints, inclusion criteria, patient population, background therapy, and assessments. The pooled polyp data suggests potential efficacy in this population, though the company will need to conduct additional studies to establish definitive therapeutic benefit.

References

1. Lyra Therapeutics reports positive results from the ENLIGHTEN 2 phase 3 tiral of LYR-210 achieving statistically significant results for primary and secondary endpoints in the treatment of chronic rhinosinusitis (CRS). News release. Lyra Therapeutics. June 2, 2025. Accessed June 3, 2025. https://www.globenewswire.com/news-release/2025/06/02/3091704/0/en/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-.html
2. Albu S. Chronic rhinosinusitis: an update on epidemiology, pathogenesis, and management. J Clin Med. 2020 Jul 18;9(7):2285. doi: 10.3390/jcm9072285
3. Lyra Therapeutics reports topline results from phase 3 ENLIGHTEN 1 trial for LYR-210 in chronic rhinosinusitis. News release. Lyra Therapeutics. May 6, 2024. Accessed June 3, 2025. https://investors.lyratherapeutics.com/news-releases/news-release-details/lyra-therapeutics-reports-topline-results-phase-3-enlighten-1