Lyra Therapeutics says ENLIGHTEN 2 trial of LYR-210 met primary endpoint

Lyra Therapeutics (LYRA) announced results from the ENLIGHTEN 2 Phase 3 clinical trial of LYR-210 in adult patients with CRS. The ENLIGHTEN 2 trial met its primary endpoint, with LYR-210 demonstrating statistically significant improvement compared to sham control in a composite of the three cardinal symptoms of CRS at week 24 in patients without nasal polyps. The ENLIGHTEN 2 trial also met the key secondary endpoints of 3CS at 24 weeks in the full population and in the clinically-validated SNOT-22 score at 24 weeks, with symptom improvement observed as early as week 4. Consistent with previous studies, LYR-210 was well-tolerated, with a safety profile similar to sham control. The ENLIGHTEN program consists of two Phase 3 clinical trials, ENLIGHTEN 1 and ENLIGHTEN 2, to evaluate the efficacy and safety of LYR-210 for the treatment of CRS. While the ENLIGHTEN 2 trial met its primary endpoint and key secondary endpoints, the ENLIGHTEN 1 trial did not meet the primary endpoint or secondary endpoints, as previously reported in May 2024. Each ENLIGHTEN trial has enrolled approximately 180 CRS patients who have failed medical management and have not had prior ethmoid sinus surgery, randomized 2:1 to either LYR-210 or sham control. The 24-week endpoints in the ENLIGHTEN trials assess LYR-210’s long-acting therapeutic effect as a bioresorbable nasal implant designed to deliver six months of continuous anti-inflammatory medication to the sinonasal passages. Results for Primary and Key Secondary Endpoints from ENLIGHTEN 2 Phase 3 Trial: Patients reported LYR-210 significantly improved important outcome measures on primary and key secondary endpoints: Statistically significant improvement compared to sham control in a composite of the 3CS of CRS at week 24in patients without nasal polyps. Statistically significant improvement in 3CS with LYR-210 compared to sham control at week 24 in the full population . Statistically significant improvements in Sino-Nasal Outcome Test score with LYR-210 compared to sham control at week 24.Improvements in SNOT-22 were observed as early as week 4 with LYR-210 compared to sham control. Improvements in SNOT-22 were sustained throughout the trial and were clinically meaningful, with more than twice the minimal clinically important difference observed at week 24 compared to baseline in the LYR-210 group. Data evaluating computed tomography scans demonstrated numerical improvement in ethmoid sinus opacification in patients who received LYR-210, compared to sham control at week 20. These data provide objective radiological evidence of improvement with LYR-210 treatment. LYR-210 patients showed no difference from sham patients in use of corticosteroid rescue medication; however, the LYR-210 patients had fewer endoscopic sinus surgeries compared to sham control. LYR-210 was well tolerated, with no product-related serious adverse events in the ENLIGHTEN 2 trial. The most commonly reported adverse events included epistaxis, upper respiratory tract infection, chronic sinusitis, acute sinusitis, nasopharyngitis, COVID-19, and headache. Results for CRS Patents with Nasal Polyps in Pooled Analysis from ENLIGHTEN 1 and ENLIGHTEN 2: Additionally, Lyra conducted a pooled data analysis of a total of 64 CRS patients with small nasal polyps from the ENLIGHTEN 1 and ENLIGHTEN 2 trials. The data demonstrated a consistent positive trend compared to sham control over 24 weeks in multiple endpoints: Improvement in 3CS with LYR-210 compared to sham control at week 24, starting as early as week 4. Improvement in SNOT-22 score with LYR-210 compared to sham control at week 24, starting as early as week 4. Improvements in percent ethmoid opacification with LYR-210 compared to sham control at week 20. Improvements in nasal congestion score with LYR-210 compared to sham control at week 24 for patients with moderate to severe NCS at baseline starting as early as week 4. Improvements in nasal polyp score with LYR-210 compared to sham control at week 24.