Lyra Therapeutics Gambles on Higher Dose in New Phase 3 Trial Following Previous Setback for Chronic Rhinosinusitis Treatment

Lyra Therapeutics is embarking on a critical new chapter in its quest to provide effective treatment for chronic rhinosinusitis (CRS), announcing the commencement of a second pivotal Phase 3 clinical trial for its drug candidate, LYR-220. This strategic move comes hot on the heels of a significant setback, where its closely related predecessor, LYR-210, failed to achieve its primary endpoint in the initial ENCORE-1 study, leading to a precipitous 70% drop in the company's stock value.

The new trial, dubbed ENCORE-2, will evaluate LYR-220, a higher-dose version of the corticosteroid-releasing implant designed for six-month efficacy.

LYR-210 and LYR-220 are both unique bioresorbable implants, placed during a routine in-office visit, engineered to continuously deliver mometasone furoate directly to the affected sinus tissues over an extended period. This targeted approach aims to reduce inflammation and symptoms associated with CRS, a debilitating condition affecting millions globally.

The previous ENCORE-1 trial, which tested LYR-210, revealed that while patients experienced clinical improvement, the study did not meet its primary endpoint of a statistically significant change from baseline in the composite SNOT-22 score compared to a sham control.

However, a glimmer of hope emerged from the secondary endpoints: LYR-210 demonstrated statistically significant improvement in specific symptoms, particularly for patients suffering from CRS with nasal polyps. This subgroup analysis offered valuable insights, suggesting a potential efficacy signal that warranted further investigation with a more potent formulation.

Indeed, earlier Phase 2 data had already hinted at LYR-220's superior efficacy compared to LYR-210.

Armed with this knowledge and the lessons learned from ENCORE-1, Lyra Therapeutics is now betting on the increased dose to deliver the robust, statistically significant results needed to secure regulatory approval and validate its innovative platform. The ENCORE-2 trial is designed to enroll 360 adult CRS patients, dividing them equally into two groups: 180 patients with nasal polyps and 180 patients without polyps, allowing for a comprehensive evaluation of LYR-220's effectiveness across the diverse CRS patient population.

Beyond LYR-220, Lyra Therapeutics is also pushing forward with LYR-210 for CRS patients without polyps.

The company highlights that in the ENCORE-1 trial, LYR-210 showed a statistically significant improvement in the total SNOT-22 score at week 24 for this specific subgroup as a secondary endpoint. This suggests a nuanced approach to treatment, potentially offering different formulations for different patient profiles.

This new trial represents a pivotal moment for Lyra Therapeutics.

The success of ENCORE-2 is not just about bringing a new treatment to market; it's also crucial for rebuilding investor confidence and demonstrating the viability of their drug delivery technology. The outcome will significantly influence the company's trajectory and its ability to address the persistent challenges faced by chronic rhinosinusitis sufferers worldwide.