EFFICACY AND SAFETY OF TOLEBRUTINIB VS. TERIFLUNOMIDE IN RELAPSING MULTIPLE SCLEROSIS: RESULTS OF THE PHASE 3 GEMINI 1 AND 2 STUDIES

OBJECTIVES: To describe the results of the phase 3 studies evaluating the efficacy and safety of tolebrutinib vs. teriflunomide in relapsing multiple sclerosis (RMS). METHODS: GEMINI-1 (NCT04410978) and GEMINI-2 (NCT04410991) are phase 3, multicenter, randomized, double-blind, double-dummy, active-controlled, parallel-group, event-driven studies. They included participants (18-55 years) with RMS; EDSS ≤5.5; and ≥1 relapse in the previous year, ≥2 relapses in the previous two years, or ≥1 gadolinium-enhancing (Gd+) T1 lesion on MRI in the previous year. Participants were randomized 1:1 (tolebrutinib 60 mg/day: teriflunomide 14 mg/day; each group with its placebo). Stratification was by EDSS at screening (<4 vs. ≥4) and region (US vs. rest). The primary endpoint was the annualized relapse rate. Secondary endpoints included disability measures, MRI outcomes, and safety. RESULTS: 1,873 participants were enrolled (GEMINI-1: n=974 and GEMINI-2: n=899) across 42 countries between June 2020 and August 2022. Mean baseline age was 36.5 years and mean time since diagnosis was 4.3 years. 67% were women, 63% were treatment-naïve, and the mean number of relapses in the previous year was 1.2. Mean EDSS was 2.38 (median 2.0; IQR: 1.5-3.0) and 34.4% had T1 Gd+ lesions at baseline. The last visit is expected in July 2024. CONCLUSION: The results of the GEMINI-1 and -2 phase 3 studies will be presented at ECTRIMS and will provide a comprehensive assessment of the efficacy and safety of tolebrutinib in participants with RMS.