#AANAM – Ublituximab Safe, Well-tolerated in Extension Study of Phase 2 Trial in Relapsing MS
The research, “Open Label Extension (OLE) of Phase 2 Multicenter Study of Ublituximab (UTX), a Novel Glycoengineered Anti-CD20 Monoclonal Antibody (mAb) in Patients with Relapsing Forms of Multiple Sclerosis (RMS)” will be presented at the American Academy of Neurology (AAN) 71st Annual Meeting, taking place May 4–10 in Philadelphia.
Ublituximab (TG-1101) is an investigational monoclonal antibody being developed by TG Therapeutics to target the immune B-cell marker protein CD20. This leads to the depletion of B-cells from the blood and central nervous system — B-cells are activated during MS relapses.
According to the company, ublituximab may be superior to current anti-CD20 treatments in MS, enabling both lower doses and shorter infusion times.
Final results of the main TG-Therapeutics-sponsored Phase 2 trial (NCT02738775) were recently presented at the 4th Annual Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) Forum, held in Dallas, Texas.
Data showed that 93% of the 48 patients enrolled (mean age 40 years) were relapse-free after a 48-week treatment with ublituximab. The annualized relapse rate — the number of relapses per year — was 0.07. In addition, median B-cell depletion was more than 99% throughout 48 weeks. Moreover, 87% of participants showed no evidence of clinical disease.
Magnetic resonance imaging (MRI) showed a complete elimination of T1 lesions at 24 and 48 weeks 24 in all 46 patients analyzed. Mean T2 lesion volume decreased by 10.6% at 48 weeks, compared with the beginning of the study. T1 lesions refer to areas of active inflammation and disease activity, while T2 lesions are a measure of the total amount of lesions, both old and new.
Ublituximab was found to be well-tolerated, and did not induce an severe treatment-related adverse events. The most frequent adverse events were infusion-related reactions. No patient had to discontinue treatment due to an ublituximab-related side effect.
At the upcoming AAN meeting, Fox will present data on both this Phase 2 trial and its open-label extension, in which 37 patients from the primary study continued receiving one-hour infusions of 450 mg of ublituximab every 24 weeks for an additional 96 weeks. Safety was monitored throughout the study, and disability assessments using the Expanded Disability Status Scale were conducted every 48 weeks.
As of October 2018, nearly 30% of participants had completed 48 weeks of treatment in the extension study.
Results showed that ublituximab continues to be well-tolerated, with no discontinuations due to adverse events.
“The Phase 2 OLE supports that one-hour infusions of UTX [ublituximab] continue to be safe and well tolerated,” the researchers wrote. Of note, five of the eight study authors are affiliated with TG Therapeutics.
The team expects additional patient follow-up data from the study to be available by the time of the AAN presentation.
According to the scientists, the results support the ongoing Phase 3 ULTIMATE program, which includes the ULTIMATE 1 (NCT03277261) and ULTIMATE 2(NCT03277248) trials. These studies are comparing the efficacy and safety of 450 mg of ublituximab with Aubagio (teriflunomide, by Sanofi Genzyme) over 96 weeks of treatment in relapsing MS patients. Both trials are led by Lawrence Steinman, MD, at Stanford University.
TG Therapeutics expects to have results from these trials as early as mid-2020.