ULTIMATE I & II Study Design and Objectives - The ULTIMATE I & II studies are identical phase 3, randomized, multi-center, double-blinded, active-controlled studies evaluating ublituximab versus teriflunomide in relapsing multiple sclerosis (RMS) patients[24] - The primary endpoint of the studies is the annualized relapse rate (ARR) at 96 weeks[31] - Key secondary endpoints include the total number of Gd-enhancing T1 lesions and new or enlarging T2 hyperintense lesions by Week 96, and the proportion of subjects with NEDA from Week 24 to Week 96[30] Efficacy Results - ULTIMATE I showed a 60% relative reduction in ARR with ublituximab (ARR 0.076) compared to teriflunomide (ARR 0.188), p < 0.0001[43] - ULTIMATE II showed a 49% relative reduction in ARR with ublituximab (ARR 0.091) compared to teriflunomide (ARR 0.178), p = 0.0022[43] - Ublituximab demonstrated a 97% relative reduction in the number of Gd+ T1 lesions in ULTIMATE I (0.016 vs 0.491) and a 96% relative reduction in ULTIMATE II (0.009 vs 0.250), both with p < 0.0001[46] - Ublituximab showed a 92% relative reduction in new or enlarging T2 lesions in ULTIMATE I (0.213 vs 2.789) and a 90% relative reduction in ULTIMATE II (0.282 vs 2.831), both with p < 0.0001[49] - A pre-specified pooled tertiary analysis showed a 100% improvement in 12-week Confirmed Disability Improvement (CDI) with ublituximab (12%) vs teriflunomide (6%), p = 0.0003[58] - A significantly higher percentage of patients treated with ublituximab achieved No Evidence of Disease Activity (NEDA) in ULTIMATE I (43.0% vs 11.4%) and ULTIMATE II (44.6% vs 15.0%), both with p < 0.0001[63] Safety and Tolerability - The most common adverse events (AEs) occurring in ≥5% of any treatment group were similar between ublituximab (N=545) and teriflunomide (N=548), with the exception of infusion-related reactions (IRR) and lymphopenia[65] - Infusion-related reactions (IRR) were more frequent with ublituximab (47.7%) compared to teriflunomide (12.2%)[65]
TG Therapeutics (TGTX) Presents ULTIMATE I & II Phase 3 Data Preview Call - Slideshow