Lyra Therapeutics Announces Phase 3 ENLIGHTEN 1 Results for LYR-210 in Chronic Rhinosinusitis

Lyra Therapeutics, Inc. recently disclosed the topline results from its Phase 3 ENLIGHTEN 1 clinical trial, which assessed the efficacy of LYR-210 in treating chronic rhinosinusitis (CRS). Unfortunately, the trial did not meet its primary endpoint of showing statistically significant improvement in a composite score of the three cardinal symptoms of CRS—nasal obstruction, nasal discharge, and facial pain/pressure—when compared to a sham control at 24 weeks. This trial is one of two pivotal studies evaluating LYR-210, a bioabsorbable sinonasal implant that delivers 7500µg mometasone furoate as a six-month treatment for CRS.

Maria Palasis, Ph.D., President and CEO of Lyra Therapeutics, expressed the company's disappointment and emphasized that they are working swiftly to analyze the full dataset to understand the trial's outcomes better and explore future directions.

The 24-week data showed the following mean improvements in the 3CS score: 2.13 (SD 2.17) points for the LYR-210 group versus 2.06 (SD 2.14) points for the sham control group, failing to reach statistical significance. In the intent-to-treat (ITT) population, LYR-210 showed a mean improvement of 2.35 (SD 2.28) points compared to 1.89 (SD 2.07) points in the sham control. Additionally, LYR-210 resulted in a mean improvement of 20.2 (SD 21.38) points in the Sino-Nasal Outcome Test (SNOT-22) score versus 15.70 (SD 18.55) points for the sham. CT scans evaluating ethmoid sinus opacification also did not show statistically significant improvement with LYR-210 treatment compared to sham control.

The treatment was generally well-tolerated, with no serious adverse events attributed to the product. Common adverse events included epistaxis, nasal odor, upper respiratory tract infections, and sinusitis.

The ENLIGHTEN 1 trial continues, with data from its 52-week extension phase expected by the fourth quarter of 2024. Additionally, ENLIGHTEN 2, another Phase 3 trial of LYR-210 for CRS, is also ongoing.

In light of these results, Lyra Therapeutics plans to make near-term operational adjustments and workforce reductions to conserve cash.

The ENLIGHTEN 1 trial involved 190 patients from the U.S. and Europe who had failed medical management for CRS and had not undergone ethmoid sinus surgery. Participants were randomized 2:1 to receive either LYR-210 or sham treatment for 24 weeks. After this period, the control group crossed over to LYR-210 treatment, while the initial LYR-210 group was re-randomized to either a sham procedure or repeat LYR-210 treatment. The baseline 3CS scores were 6.9 points for the treatment group and 6.7 points for the control, with SNOT-22 scores averaging 61 points for both groups. Baseline CT opacification scores were 44.9% for the treatment group and 47.3% for the control.

LYR-210 is designed as a bioabsorbable sinonasal implant offering six months of continuous mometasone furoate delivery to CRS-affected sinonasal passages. CRS is a prevalent inflammatory condition of the paranasal sinuses, significantly impacting patients' quality of life. Lyra Therapeutics' product candidates, LYR-210 and LYR-220, aim to provide a long-acting solution for CRS treatment. LYR-210 is intended for patients with standard nasal anatomy who have not had prior ethmoid sinus surgery. LYR-220 is tailored for patients with an enlarged nasal cavity due to previous surgery.

Lyra Therapeutics, Inc. is a clinical-stage biotechnology company focusing on developing sinonasal implants for CRS, aiming to address the needs of the approximately four million CRS patients in the U.S. who do not respond to current medical treatments.