TG Therapeutics announced positive topline results from two global, active-controlled, Phase 3 studies, called ULTIMATE I & II, evaluating ublituximab compared to Aubagio (teriflunomide) in patients with relapsing forms of multiple sclerosis (RMS). Both studies met their primary endpoint with ublituximab treatment demonstrating a statistically significant reduction in annualized relapse rate (ARR) over a 96-week period. Ublituximab treatment resulted in an ARR of <0.10 in each of ULTIMATE I & II, with a relative reduction in ARR of approximately 60% and 50%, respectively, over teriflunomide.
ULTIMATE I and ULTIMATE II are independent Phase 3, randomized, double-blinded, active-controlled, global, multi-center studies evaluating the efficacy and safety/tolerability of ublituximab (450mg dose administered by one-hour intravenous infusion every 6 months, following a Day 1 infusion of 150mg over four hours and a Day 15 infusion of 450mg over one hour) versus teriflunomide (14mg oral tablets taken once daily) in subjects with relapsing forms of Multiple Sclerosis (RMS). The primary endpoint for each study was Annualized Relapse Rate (ARR) following 96 weeks of treatment. Secondary endpoints include total number of T1 gadolinium-enhancing lesions, total number of new and/or enlarging T2 hyperintense lesions, and time to confirmed disability progression (CDP). The ULTIMATE I & II trials enrolled a total of 1,094 patients with RMS across 10 countries. Both studies were conducted under Special Protocol Assessment (SPA) agreement with the U.S. FDA.
Further analyses of the ULTIMATE I & II studies including safety and secondary endpoints will be conducted and detailed data will be presented at an upcoming medical congress, targeted in first half of 2021.
TG Therapeutics plans to use the data from these studies to support a Biologics License Application (BLA) submission for ublituximab in RMS targeted in mid-year 2021.
Ublituximab is a glycoengineered monoclonal antibody that targets a unique epitope on CD20-expressing B cells. When ublituximab binds to the B cell it triggers a series of immunological reactions (including antibody-dependent cellular cytotoxicity [ADCC] and complement dependent cytotoxicity [CDC]), leading to destruction of the cell. Additionally, ublituximab is uniquely designed, to lack certain sugar molecules normally expressed on the antibody. Removal of these sugar molecules, a process called glycoengineering, has been shown to enhance the potency of ublituximab, especially the ADCC activity.
Targeting CD20 using monoclonal antibodies has proven to be an important therapeutic approach for the management of B-cell malignancies and autoimmune disorders, both diseases driven by the abnormal growth or function of B cells.