Search

BACKGROUND: Matching-adjusted indirect comparison (MAIC) is a methodology for cross-study comparisons after adjusting for baseline characteristic imbalances. It is a comparative analytical approach used across therapeutic areas absent head-to-head trial outcomes. OBJECTIVE: To compare the efficacy of OC-01 (varenicline solution) 0.03 mg nasal spray (OC-01 VNS) to lifitegrast 5% ophthalmic solution on tear production and patient-reported eye dryness in patients with dry eye disease (DED) using data from phase 3 clinical trials via MAIC analysis. METHODS: Individual patient data (IPD) from the phase 3 registrational trial of OC-01 VNS and aggregate data from 2 phase 3 trials of lifitegrast in the publicly available XIIDRA New Drug Application were used. Using unanchored MAIC methods, IPD were weighted on clinically relevant baseline variables (age, race, sex, baseline Schirmer's test score [STS], and Eye Dryness Score [EDS]) to produce weighted OC-01 VNS datasets matched to the same lifitegrast datasets' variables. Least-squares (LS) mean change from baseline (CFB) in STS for OC-01 VNS was calculated using the identical analysis of covariance model and covariates used to calculate the same values for lifitegrast in the XIIDRA New Drug Application and was then compared. LS mean EDS (based on a 100- point Visual Analogue Scale) was compared via analysis of covariance in the weighted OC-01 VNS and lifitegrast datasets. OC-01 VNS at 2 and 4 weeks compared to lifitegrast data at 2 and 6 weeks. RESULTS: Data from 511 subjects (n = 260 treated; 251 vehicle control [VC]) in the OC-01 VNS phase 3 trial, 588 (n = 293 treated, 295 VC) in the lifitegrast phase 3 OPUS-1 trial, and 718 (n = 358 treated, 360 VC) in the lifitegrast phase 3 OPUS-2 trial were analyzed. The LS mean STS CFB for OC-01 VNS at 2 and 4 weeks was significantly greater than that for lifitegrast at 2 and 6 weeks in OPUS-1 and OPUS-2 ( P < 0.0001 for all comparisons). The LS mean EDS CFB for OC-01 VNS at 2 and 4 weeks was significantly greater than that for lifitegrast at 2 and 6 weeks in OPUS-1 ( P < 0.0001 for both comparisons) and at 4 weeks vs lifitegrast at 6 weeks in OPUS-2 ( P < 0.0001). CONCLUSIONS: This MAIC analysis demonstrates OC-01 VNS produced significantly greater improvement in mean STS and comparable or greater improvement in EDS compared with lifitegrast in phase 3 trials. These findings suggest a potentially greater magnitude of improvement achieved with OC-01 VNS compared with lifitegrast for the treatment of DED within the conditions of the analysis methodology. DISCLOSURES D White is a consultant for Oyster Point Pharma, Inc. L Hendrix, M Macsai, and A Gibson are employees and shareholders for Oyster Point Pharma, Inc. L Sun was an employee of COEUS, Clinical Research at the time of study conduct and received funding from Oyster Point Pharma, Inc. I Tam is an employee of COEUS, Clinical Research and received funding from Oyster Point Pharma, Inc. Oyster Point Pharma, Inc was involved in the study design, data collection, data analysis, and preparation of the manuscript and is the manufacturer/licensee of OC-01 (varenicline solution) nasal spray. Oyster Point Pharma, Inc., sponsored the phase 3 OC-01 (varenicline solution) clinical study from which analysis data were obtained.

BACKGROUND: Matching-adjusted indirect comparison (MAIC) is a validated and widely accepted statistical method that derives indirect comparisons between treatments when head-to-head studies have not been performed. OBJECTIVE: To compare the efficacy of OC-01 varenicline nasal spray (OC-01 VNS) 0.03 mg to cyclosporine A (CsA) 0.05% ophthalmic emulsion on tear production in patients with dry eye disease based on data from the respective phase 3 clinical trials using the MAIC technique. METHODS: Individual patient data were drawn from the phase 3 registry trial of OC-01 VNS; aggregate data were drawn from 2 phase 3 trials of CsA in the publicly available New Drug Application for CsA 0.05% ophthalmic emulsion (RESTASIS). Using unanchored MAIC methods, the individual patient data were weighted based on 4 clinically relevant baseline variables (age, race, sex, and baseline Schirmer test score [STS]) to produce a weighted OC-01 VNS dataset matched to the key demographics of the CsA dataset. Least-squares mean change from baseline in STS for OC-01 VNS was calculated using the identical analysis of variance model used to calculate the same value for CsA in the RESTASIS New Drug Application, which were then compared. Proportions of subjects with improvement of 10 mm or more from baseline in STS were compared in the weighted OC-01 VNS and CsA dataset. Time points available for comparisons were CsA trials at 3 and 6 months and OC-01 data at 2 and 4 weeks. RESULTS: Data from 511 subjects in the OC-01 VNS phase 3 trial and 585 in the CsA phase 3 trials were analyzed. The least-squares mean STS change from baseline for OC-01 VNS at 2 and 4 weeks was significantly higher than that for CsA at 3 and 6 months ( P < 0.0001 for all comparisons). Mean STS improvements were approximately 6-7 mm for OC-01 VNS and approximately 1 mm for CsA. The proportion of subjects with improvement of 10 mm or more from baseline in STS was significantly higher for OC-01 VNS (50.2%) than CsA (11.7 and 17.1% in the 2 CsA studies; P < 0.0001 for both comparisons). CONCLUSIONS: This MAIC analysis demonstrates OC-01 VNS produces significantly greater improvement in mean STS and results in significantly greater numbers of patients with substantial improvement in STS (percentage ≥ 10 mm) compared with CsA. Together, absent more robust data from head-to-head trials, findings may suggest a potentially greater magnitude of improvement achieved with OC-01 VNS compared with CsA for the treatment of dry eye disease within conditions of the analysis methodology. DISCLOSURES: Dr Visco was a consultant for Novartis, Allergan, and Oyster Point, Inc. Ms Hendrix and Drs Macsai and Gibson are employees and shareholders for Oyster Point Pharma, Inc. Drs Sun and Tam participated in clinical research and received funding from Oyster Point Pharma, Inc. Oyster Point Pharma, Inc sponsored the Phase 3 OC-01 (varenicine solution) clinical study from which analysis data are obtained.