Positive Phase 2 Data for Ublituximab as Treatment for Relapsing Multiple Sclerosis

Ublituximab may provide a clinical benefit for patients with multiple sclerosis via lower doses and faster infusion times than current therapies.

New data from a phase 2 clinical trial evaluating ublituximab (TG-1101) for relapsing multiple sclerosis (RMS) showed positive results, according to a poster presentation at the Annual Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) forum.1

Ublituximab, a novel glycoengineered anti-CD20 monoclonal antibody being developed by TG Therapeutics, targets a specific and unique epitope on the CD20 antigen found on mature B-lymphocytes. Previous oncology studies have showed robust activity in patients with various B-cell mediated diseases.1

The phase 2 program aimed to evaluate whether the enhanced antibody-dependent cellular cytotoxicity potency of ublituximab can translate into the additional clinical benefits for patients with MS in the form of lower doses and faster infusion times than current therapies, according to the researchers.1

In this study, 48 patients were enrolled through 48 weeks of treatment and received either ublituximab or placebo administered via intravenous infusion on days 1, 15, and week 24. To qualify for the study, participants needed to have a diagnosis of relapsing MS and have either 1 confirmed MS relapse in the past year, 2 relapses in the past 2 years, or at least 1 active Gd-enhancing T1 lesion at the screening MRI.1

The data showed that by the end of the study, an annualized relapse rate of 0.07 was observed, with 93% of patients relapse-free at week 48. Additionally, a median B cell depletion of >99% was demonstrated at the primary analysis point of week 4, and maintained at weeks 34 and 48.1

At baseline, 39% of patients had ≥1 T1 Gd lesions and 26% had ≥4 Gd lesions. Treatment with ublituximab eliminated 100% of T1 Gd-enhancing lesions in all patients at week 24 and maintained complete elimination at week 48. A 10.6% reduction in T2 lesion volume was also observed over the treatment period, according to the results.1

Overall, ublituximab demonstrated tolerability, with the most common adverse events (AEs) being infusion-related reactions. No drug-related discontinuations occurred in the trial. A rapid infusion time as low as 1 hour of 450 mg was also well-tolerated and produced high levels of B cell depletion, the researchers concluded. The dose is now being studied in the ongoing phase 3 ULTIMATE trials in MS.2

“We believe our phase 2 data present a compelling profile of best-in-class activity coupled with a convenient 1-hour infusion,” Michael S. Weiss, executive chairman and chief executive officer of TG Therapeutics, said in a statement.2 “With our phase 3 ULTIMATE program fully enrolled, we are looking forward to the results next year.”

References

  • Fox E, Lovett-Racke A, Liu Y, et al. Final results of a placebo-controlled, phase 2 multicenter study of ublituximab (UTX), a novel glycoengineered anti-CD20 monoclonal antibody (mAb), in patients with relapsing forms of multiple sclerosis (RMS). Poster presented at: Americas Committee for Treatment and Research in Multiple Sclerosis; October 2018; Dallas, TX.

  • TG Therapeutics, Inc. Announces Final Phase 2 Multiple Sclerosis Data Presentation at the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) Annual Meeting [news release]. http://ir.tgtherapeutics.com/news-releases/news-release-details/tg-therapeutics-inc-announces-final-phase-2-multiple-sclerosis-1. Published March 1, 2019. Accessed March 5, 2019.