Lyra Therapeutics announced disappointing topline results from its Phase 3 ENLIGHTEN 1 trial, which failed to demonstrate statistically significant improvement for LYR-210 in treating chronic rhinosinusitis (CRS) compared to sham control. The bioabsorbable sinonasal implant did not meet its primary endpoint of improving the composite score of three cardinal CRS symptoms at 24 weeks.
"We are surprised and disappointed by the ENLIGHTEN 1 topline results," said Maria Palasis, Ph.D., President and Chief Executive Officer of Lyra Therapeutics. "We are moving as quickly as possible to evaluate the full dataset to better understand these findings in order to determine our path forward."
Trial Design and Patient Population
ENLIGHTEN 1 was a randomized, blinded, sham-controlled trial that enrolled 190 patients with chronic rhinosinusitis who had failed medical management and had not undergone prior ethmoid sinus surgery. Patients were randomized 2:1 to receive either LYR-210 or sham control for 24 weeks, with approximately two-thirds of participants recruited from U.S. sites and one-third from European sites.
The trial population had mean baseline composite symptom scores (3CS) of 6.9 points in the treatment arm and 6.7 points in the sham control arm. Both groups showed similar baseline SNOT-22 scores of 61 points, while CT opacification scores were 44.9% and 47.3% for treatment and sham control arms, respectively.
Primary Endpoint Results
At 24 weeks, LYR-210 failed to achieve statistical significance in the primary efficacy analysis. Treatment with LYR-210 resulted in a mean improvement in the 3CS score of 2.13 points (standard deviation 2.17), compared to 2.06 points (standard deviation 2.14) in the sham control group.
In the intent-to-treat population, LYR-210 showed a mean improvement of 2.35 points (standard deviation 2.28) in the 3CS score, compared to 1.89 points (standard deviation 2.07) for sham control. The SNOT-22 scores improved by 20.2 points (standard deviation 21.38) with LYR-210 versus 15.70 points (standard deviation 18.55) with sham control in the intent-to-treat population.
Ethmoid sinus opacification, evaluated by computed tomography scans, also failed to show statistically significant improvement after LYR-210 treatment compared to sham control.
Safety Profile
LYR-210 demonstrated a generally favorable safety profile with no product-related serious adverse events reported. The most commonly observed adverse events in the study population included epistaxis, nasal odor, upper respiratory tract infection, and sinusitis.
About LYR-210 and Market Opportunity
LYR-210 is designed as a bioabsorbable sinonasal implant that delivers 7500 μg of mometasone furoate over six months of continuous anti-inflammatory treatment to the sinonasal passages. The investigational treatment targets up to four million CRS patients in the United States who fail current therapies annually and require further intervention.
Chronic rhinosinusitis represents a highly prevalent inflammatory disease of the paranasal sinuses that causes debilitating symptoms and significant morbidities, ranking as the fifth most common condition in people under age 65.
Company Response and Future Plans
Following the trial results, Lyra Therapeutics expects to implement near-term changes to its business operations and reduce its workforce to preserve cash resources. The company continues to operate ENLIGHTEN 2, its second pivotal Phase 3 trial evaluating LYR-210 in CRS patients.
The ENLIGHTEN 1 trial remains ongoing, with 52-week extension phase data expected in the fourth quarter of 2024. The company plans to evaluate the complete dataset to inform its path forward, including decisions regarding the ongoing ENLIGHTEN 2 study.
Lyra Therapeutics also develops LYR-220, a larger implant designed for CRS patients whose nasal cavity has been enlarged due to previous ethmoid sinus surgery. Both LYR-210 and LYR-220 are intended for administration through simple, in-office procedures and deliver six months of continuous anti-inflammatory drug therapy with a single administration.
