Impact of long‐acting implantable LYR‐210 corticosteroid matrices on quality of life of patients with chronic rhinosinusitis in the LANTERN study

Chronic rhinosinusitis (CRS) is a highly prevalent disorder with a decreased quality of life (QoL).1 Persistent sinonasal symptoms, fatigue, sleep disruption, and depression negatively affect the well-being and productivity of CRS patients.1 Intranasal corticosteroid sprays fail to adequately control symptoms in all CRS patients due to inconsistent delivery of effective corticosteroid doses deep into the sinuses, rapid mucosal clearance, and poor compliance.1-3 Limitations of current CRS therapies demonstrate the need for long-acting, local anti-inflammatory treatments that provide targeted therapy to the sinonasal mucosa and improve symptoms and QoL. LYR-210, a bioresorbable matrix designed by Lyra Therapeutics (Watertown, MA, USA) to continuously deliver mometasone furoate (MF) to the sinonasal mucosa for 24 weeks, is in clinical development for surgically naïve CRS patients who failed previous medical management. In the phase 2 LANTERN study, LYR-210 (7500 μg) demonstrated significant global CRS symptom improvements based on 22-item Sino-Nasal Outcome Test (SNOT-22) total scores compared to the control.4 All LYR-210 (7500 μg)-treated subjects achieved the minimal clinically important difference (MCID) of 8.9 points5 for the SNOT-22 total score at week 24.4 Treatment-related adverse events reported in this study are consistent with MF's safety profile.4, 6 This article describes the impact of LYR-210 on the QoL of CRS patients from the LANTERN study via the change from baseline in SNOT-22 subdomains and 36-Item Short Form Health Survey version 2 (SF-36v2) at week 24. The multicenter, patient-blinded, randomized, controlled LANTERN study evaluated LYR-210 in CRS patients who failed previous medical management and had no prior endoscopic sinus surgery (NCT04041609). The study was conducted in accordance with the Declaration of Helsinki and Good Clinical Practice guidelines. The study protocol and patient-informed consent were approved by each site's Institutional Review Board. Subjects were randomized to receive bilateral administration of LYR-210 (2500 μg) (N = 23) or LYR-210 (7500 μg) (N = 21) into the middle meatus, or sham-procedure (control) (N = 23). LYR-210 was removed or sham-procedure in the control group was performed at week 24. Study design, inclusion/exclusion criteria, and methodologies were previously reported.4 The SNOT-22 is a validated CRS-specific QoL questionnaire comprised of five subdomains: rhinologic (0–30 score), extra-nasal rhinologic (0–15 score), ear/facial (0–25 score), psychological dysfunction (0–35 score), and sleep dysfunction (0–25 score).7 SNOT-22 was completed at baseline (pre-procedure) and weeks 2, 4, 8, 12, 16, 20, and 24 (pre-removal). The SF-36v2 is a validated non-disease-specific patient-reported outcome instrument that provides scores for eight health domains (vitality, social functioning, role-emotional, mental health, physical functioning, role-physical, bodily pain, and general health), psychometrically-based physical component summary (PCS) and mental component summary (MCS).8 Higher scores represent better QoL. SF-36v2 was completed at baseline (pre-procedure) and week 24 (pre-removal). Subjects with baseline and subsequent assessments were analyzed. Missing data and data post-rescue medication use were imputed using last obervation carried forward (LOCF) for SNOT-22 subdomain scores. Change from baseline in SNOT-22 subdomain and SF-36v2 scores at week 24 were pre-specified in the study protocol and analyzed using analysis of covariance (ANCOVA). Comparisons between groups were conducted at a one-sided significance level of 0.05. No adjustments were made for multiple comparisons. A clinically meaningful response in a SNOT-22 subdomain is an improvement from baseline equal to or greater than the MCID for that subdomain.9 Mean differences between groups in SF-36v2 were clinically relevant if they met minimal important difference thresholds.8 Baseline scores for SNOT-22 subdomains and SF-36v2 were comparable between groups. At week 24, LYR-210 (7500 μg) demonstrated significant improvements in each SNOT-22 subdomain versus control, with mean decreases of 10.0, 8.0, 5.2, 15.2, and 10.3 points from baseline in the rhinologic, ear/facial, extranasal rhinologic, psychological dysfunction, and sleep dysfunction scores, respectively (Figure 1). LYR-210 (2500 μg) significantly improved sleep dysfunction versus control at week 24. The observed response appeared to be dose-dependent. Higher proportions of LYR-210 (7500 μg)-treated subjects achieved the MCIDs for the SNOT-22 subdomains9 versus control at week 24. At week 24 in the SF-36v2, LYR-210 (7500 μg)-treated subjects reported mean increases of 10.2, 11.4, 11.7, 8.7, and 9.8 points from baseline in the MCS, vitality, social functioning, role-emotional, and mental health scores, respectively, that were significantly better than control (Figure 2A). LYR-210 (2500 μg)-treated subjects reported significant improvements in the MCS and three mental health domains versus control at week 24. LYR-210 (7500 μg) also achieved significant improvements at week 24 versus control in physical functioning, role-physical, and bodily pain scores, with mean increases of 8.4, 8.4, and 10.6 points from baseline, respectively. LYR-210 (7500 μg) increased mean PCS and general health scores by 8.1 and 8.5 points from baseline, respectively, at week 24 (Figure 2B). LYR-210 (2500 μg) significantly improved bodily pain versus control and numerically improved the other physical health domains at week 24. The significant improvements LYR-210 (7500 μg) achieved in the MCS, four mental health domains, and three physical health domains of the SF-36v2 at week 24 were clinically meaningful.8 LYR-210 (7500 μg) provided clinically meaningful improvements in the QoL of CRS patients at week 24 in the LANTERN study. The SNOT-22 subdomain results are consistent with the ∼40-point improvement from baseline in the SNOT-22 total score for LYR-210 (7500 μg).4 LYR-210 (7500 μg)-treated subjects on average reported >2× the MCIDs for the SNOT-22 subdomains9 at week 24. LYR-210 demonstrated a dose response in the SNOT-22 total4 and subdomain scores at week 24. LYR-210-treated subjects also reported higher SF-36v2 scores than the control. The PCS and general health domain scores were not statistically significant between groups, possibly due to the small sample size. There was no apparent dose response observed for SF-36v2 at week 24, which may be because SF-36v2 is a generic QoL assessment that measures general mental and physical health, and unlike the SNOT-22, the questions are not specific to CRS symptoms. SF-36v2 improvement with LYR-210 (7500 μg) in this study is consistent with other products that have been evaluated in CRS.10 Because CRS has a high disease burden,1 treatments that improve QoL may fill an unmet need for the management of CRS. If the LANTERN results are confirmed in the ongoing pivotal studies (NCT05219968, NCT05295459), LYR-210 (7500 μg) may be a promising treatment that could improve the QoL of CRS patients. We thank the patients, clinical site investigators, and study coordinators for their participation in this study. Lyra Therapeutics, Inc. was the sponsor of this clinical study. J. Rimmer, A. Cervin, and A. Wrobel were investigators in the LANTERN study; J. Shao is a former employee and A. Gartung, L. Brayton, and V. Belanger are employees of and have stock options at Lyra Therapeutics, Inc.