Lyra Therapeutics, Inc. announced the enrollment of the first patient in the Phase 3 ENLIGHTEN II clinical trial of LYR-210 in adult patients with chronic rhinosinusitis (CRS). LYR-210 is designed as an alternative to sinus surgery for the millions of CRS patients that remain symptomatic despite treatment. ENLIGHTEN II is the second Phase 3 trial in the pivotal clinical program for LYR-210, along with the ENLIGHTEN I trial that was initiated earlier this year.

The two ENLIGHTEN trials will enroll surgically-naïve CRS patients in the U.S. and Europe to support a New Drug Application to the U.S. Food and Drug Administration for LYR-210. The ENLIGHTEN program consists of two Phase 3 studies expected to include a total of 360 adult, surgically-naïve CRS patients. ENLIGHTEN II is a multicenter, randomized, controlled trial to evaluate the efficacy and safety of LYR-210 (7500µg MF) compared to control.

The trial will enroll approximately 180 CRS patients who have failed medical management and have not had prior sinus surgery, randomized 2:1 to either LYR-210 (7500µg MF) or control. The primary endpoint of the trial is the change from baseline in a composite score of three cardinal symptoms (3CS) of CRS (i.e., nasal blockage, nasal discharge, and facial pain) at week 24. LYR-210 is an investigational product candidate that utilizes Lyra's proprietary XTreoTM platform to enable six months of local, intra-nasal, anti-inflammatory therapy from a single treatment for CRS.

LYR-210 is designed as a non-invasive alternative to sinus surgery for the millions of CRS patients who have failed medical management. LYR-210 is a bioresorbable polymeric matrix designed to be administered in a brief in-office procedure and is intended to deliver up to six months of continuous mometasone furoate (MF) drug therapy to the sinonasal passages. In the LANTERN Phase 2 study, LYR-210 (7500 µg) demonstrated rapid, clinically meaningful and durable symptom improvement in a composite score of CRS cardinal symptoms over six months.

These results were supported in the Phase 2 LANTERN 6-month post treatment evaluation which showed a durable response in about 50% of treated CRS patients six months post LYR-210 removal. A pharmacokinetic (PK) study showed that MF blood levels were constant over the 56-day treatment period, confirming that LYR-210 delivers a steady daily dose of MF with accompanying rapid symptom relief during this time period. There are approximately 14 million patients with CRS in the US, approximately four million of whom fail current standard of care medical management.

CRS is a highly prevalent inflammatory disease of the paranasal sinuses which leads to debilitating symptoms and significant morbidities and is the fifth most common condition in people under 65. Cardinal symptoms include nasal obstruction and congestion, facial pain and pressure, nasal discharge, and olfactory loss. The prevalence of CRS in the U.S. is estimated to be 14 million, with 8 million treated annually using medical management including topical steroid sprays and oral steroids.

Roughly half of those treated fail and seek alternative medical intervention. While ENT physicians perform approximately 400,000 surgeries annually for CRS, 65% of patients have recurrent symptoms and 100% require ongoing medical management. Additionally, many patients are surgery unwilling as the current procedures are invasive, not curative, and often require long recovery times.