Ublituximab trials in Multiple Sclerosis

 TG Therapeutics, Inc. announced data from the ULTIMATE I & II Phase 3 trials evaluating ublituximab in patients with relapsing forms of multiple sclerosis (RMS) at the American Academy of Neurology (#AAN2022) annual meeting, 2-7 April 2022 in Washington, USA. Highlights of the presentations are outlined below.

We are pleased to present additional analyses from the ULTIMATE I & II trials, which continue to highlight encouraging data for ublituximab as a potential treatment for patients with relapsing forms of multiple sclerosis. Of note, post hoc/pooled analyses demonstrate approximately 95% of ublituximab treated patients who demonstrated 12-week CDI sustained the improvement through the end of the study at week 96, a consistent NEDA benefit for ublituximab-treated patients was demonstrated across treatment epochs and key patient subpopulations, and 96% of patients completed their ublituximab infusions without interruptions. We believe these data reinforce the potential of ublituximab, if approved, to offer RMS patients a treatment option that can be administered in a one-hour infusion every six months after the first dose.

Michael S. Weiss, Chairman and Chief Executive Officer of TG Therapeutics

Poster Presentation Title: Disability Improvements With Ublituximab in Relapsing Multiple Sclerosis (RMS): Expanded Disability Status Scale (EDSS), 9-Hole Peg Test (9-HPT), and Timed 25-Foot Walk   (T25FW) Evaluations From the Phase 3 ULTIMATE I and II Studies

  • In pooled post hoc analyses of ULTIMATE I and II:
    • Among ublituximab patients who demonstrated 12-week Confirmed Disability Improvement (CDI), 95.4% (62/65) sustained the improvement through the end of the study at week 96.
    • In patients with a baseline Expanded Disability Status Score (EDSS) score ≥2.0, more patients in the ublituximab group than teriflunomide group had EDSS improvements of 1.0 and 1.5 points at Weeks 60, 72, 84, and 96 (P<0.05 for all)
    • At 96 weeks, a ≥20% improvement in 9-HPT was observed in 11.4% and 5.5% (dominant hand; P=0.0009) and 11.4% and 5.7% (nondominant hand; P=0.0016) of ublituximab (n=543) and teriflunomide (n=546) treated patients, respectively

Poster Presentation Title: Ublituximab Treatment Is Associated With a Significant Proportion of Patients Achieving No Evidence of Disease Activity (NEDA): Results From the Ultimate I and Ultimate II Phase 3 Studies of Ublituximab vs Teriflunomide in Relapsing Multiple Sclerosis (RMS)

  • ULTIMATE I and II post hoc pooled analyses demonstrated a consistent NEDA benefit for ublituximab treated patients across treatment epochs and key patient subpopulations
  • In pooled post hoc analyses evaluating NEDA-3 by treatment epoch and patient subtype:
    • NEDA-3 rates for ublituximab vs teriflunomide cohorts by treatment epoch at 0-96 weeks were 44.6% (232/520) vs 12.4% (65/524), respectively, and at 24-96 weeks (re-baselined) were 82.1% (418/509) vs 22.5% (115/511) (P<0.0001 for both)
    • NEDA-3 at 24-96 weeks (re-baselined) was achieved in 82.7% (268/324) vs 23.1% (81/350) of treatment-naive, 81.1% (34/161) vs 21.1% (150/185) of previously treated (prior disease-modifying therapy [DMT]), 82.4% (206/250) vs 18.6% (48/258) of early-disease, and 81.9% (212/259) vs 26.5% (67/253) of late-disease patients in ublituximab- vs teriflunomide-treated cohorts, respectively (P<0.0001 for all)
    • The leading cause of disease activity during Weeks 24-96 (re-baselined) was new/enlarging T2 lesions for teriflunomide (occurring in 71.6% of patients) and relapse for ublituximab (occurring in 11.4% of patients)

Poster Presentation Title: Infusion-Related Reactions (IRRs) With Ublituximab in Patients With Relapsing Multiple Sclerosis (RMS): Post Hoc Analyses From the Phase 3 ULTIMATE I and II Studies

  • In pooled analyses of the ULTIMATE studies, 96.6% of patients (n=545) completed ublituximab infusions without interruption, and 94.6% completed Dose 2-5 maintenance infusions within 1 hour±5 minutes
  • 43% of patients had an IRR at Dose 1, the proportion of patients experiencing an IRR markedly decreased to <10.0% for all subsequent infusions, and 69.5% did not have an IRR recurrence
  • 78.8% of Dose 1 and 69.2% of Dose 2 IRRs with ublituximab occurred during the infusion period or within 1 hour post infusion
  • The administration route of premedications (oral, intravenous [IV], intramuscular [IM], or mixed) did not impact the frequency of IRRs
  • IRRs were the prevailing adverse event (AE) with ublituximab in ULTIMATE I and II; the vast majority were mild to moderate in severity

The above presentations are available on the Publications page, located within the Pipeline section, of the Company’s website at http://www.tgtherapeutics.com/publications.cfm.

ULTIMATE I and ULTIMATE II are two independent Phase 3, randomised, 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 ULTIMATE I & II trials enrolled a total of 1,094 patients with RMS across 10 countries. These trials were led by Lawrence Steinman, MD, Zimmermann Professor of Neurology & Neurological Sciences, and Pediatrics at Stanford University and were conducted under a Special Protocol Assessment (SPA) agreement with the U.S. Food and Drug Administration (FDA). As previously announced, both studies met their primary endpoint with ublituximab treatment demonstrating a statistically significant reduction in annualized relapse rate (ARR) compared to terifunomide over a 96-week period (p<0.005 in each trial). Additional information on these clinical trials can be found at http://www.clinicaltrials.gov (NCT03277261; NCT03277248).

Ublituximab is an investigational 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.

TG Therapeutics is a fully-integrated, commercial stage biopharmaceutical company focused on the acquisition, development and commercialisation of novel treatments for B-cell malignancies and autoimmune diseases. In addition to an active research pipeline including five investigational medicines across these therapeutic areas, TG has received accelerated approval from the U.S. FDA for UKONIQ® (umbralisib), for the treatment of adult patients with relapsed/refractory marginal zone lymphoma who have received at least one prior anti-CD20-based regimen and relapsed/refractory follicular lymphoma who have received at least three prior lines of systemic therapies. Currently, the Company has three programmes in Phase 3 development for the treatment of patients with relapsing forms of multiple sclerosis (RMS) and patients with chronic lymphocytic leukemia (CLL) and several investigational medicines in Phase 1 clinical development. For more information, visit http://www.tgtherapeutics.com

UKONIQ® is a registered trademark of TG Therapeutics, Inc.