Benzinga | Apr 16, 2021 07:36AM EDT

TG Therapeutics To Present Results From ULTIMATE I & II Phase 3 Trials Of Ublituximab

Ublituximab demonstrated superiority versus teriflunomide in reducing annualized relapse rates and MRI brain lesions

Ublituximab was generally well tolerated, with no unexpected safety signals

BLA submission targeted in Q3 2021

Webcast to be held today, Friday, April 16, 2021 at 8:30 AM ET

TG Therapeutics, Inc. (NASDAQ:TGTX), today announced positive results from two global, active-controlled, Phase 3 studies, called ULTIMATE I & II, evaluating ublituximab, the Company's investigational novel, glycoengineered anti-CD20 monoclonal antibody, compared to 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 (p<0.005 in each trial). Key secondary MRI endpoints were also met.

These data will be previewed on a call today and presented at the American Academy of Neurology (AAN) 73rd Annual Meeting, tomorrow April 17, 2021. Details of each event are included below.

Lawrence Steinman, MD, Zimmermann Professor of Neurology & Neurological Sciences, and Pediatrics at Stanford University and Global Study Chair for the ULTIMATE I & II studies commented, "The results of the ULTIMATE I & II studies show that not only did ublituximab effectively reduce relapses in patients with RMS, but had a profound effect on suppressing inflammatory activity, evident by the reduction in both T1 Gd enhancing lesions as well as T2 lesions. Taken together, historically low ARRs, marked reductions in brain lesions and very low rates of confirmed disability progressions resulted in nearly half of the patients treated with ublituximab achieving no evidence of disease activity, a goal we strive for when treating our patients with RMS, which continues to be a challenge to achieve." Dr. Steinman continued, "Today represents an exciting day for RMS patients who continue to need efficacious and convenient treatment options."

Michael S. Weiss, Executive Chairman and Chief Executive Officer of TG Therapeutics stated, "We are extremely pleased with the results from the ULTIMATE I & II Phase 3 trials. We believe these data showcase ublituximab to be a highly efficacious treatment option with a generally well tolerated safety profile. If approved, ublituximab will be the only CD20 offered in a convenient one-hour infusion every six months, following the first dose. We look forward to sharing these results during our webcast and at AAN and are targeting a BLA submission for ublituximab to treat patients with RMS in the third quarter of this year."

The ULTIMATE I & II studies investigated the safety and efficacy of a one-hour 450mg infusion of ublituximab every six months, following the Day 1 infusion (150mg over four hours). The studies were conducted under Special Protocol Assessment (SPA) agreement with the U.S. Food and Drug Administration (FDA). Additionally, data from these studies are intended to support a Biologics License Application (BLA) submission for ublituximab in RMS targeted in the third quarter of 2021.

Data highlights from the ULTIMATE I & II Phase III studies in patients with RMS include:

Primary Endpoint: Annualized Relapse Rate (ARR) Results

* In ULTIMATE I, treatment with ublituximab resulted in an ARR of 0.076 compared to 0.188 for teriflunomide, representing a relative reduction of approximately 60% (p<0.0001).

* In ULTIMATE II, treatment with ublituximab resulted in an ARR of 0.091 compared to 0.178 for teriflunomide, representing a relative reduction of approximately 50% (p=0.0022).

MRI Results

* Total number of T1 Gadolinium (Gd) enhancing lesions were reduced as a result of ublituximab treatment by 97% and 96% relative to treatment with teriflunomide in ULTIMATE I & II, respectively (p<0.0001).

* New or enlarging T2 lesions were reduced as a result of ublituximab treatment by 92% and 90% relative to treatment with teriflunomide in ULTIMATE I & II, respectively (p<0.0001).

No Evidence of Disease Activity (NEDA) Results

* In ULTIMATE I, 44.6% of ublituximab treated patients achieved NEDA representing a 198% improvement over teriflunomide (p <0.0001).

* In ULTIMATE II, 43% of ublituximab treated patients achieved NEDA representing a 277% improvement over teriflunomide (p<0.0001).

Prespecified Pooled Disability Results

* A very low rate of disability progression was observed across all treatment groups. Only 5.2% of ublituximab treated patients showed a 12-week Confirmed Disability Progression (CDP), compared to 5.9% with teriflunomide, and only 3.3% of ublituximab treated patients showed a 24-week CDP, compared to 4.8% with teriflunomide; neither was statistically different.

* Ublituximab treatment increased the proportion of patients with 12-week Confirmed Disability Improvement (CDI) and 24-week CDI, demonstrating a 100% improvement in 12-week CDI (12% v. 6%; p=0.0003), and an 88% improvement in 24-week CDI (9.6% v. 5.1%; p=0.0026) compared to teriflunomide.

Ublituximab was generally well tolerated with no unexpected safety signals. Overall, the proportion of patients in the ublituximab group with adverse events was similar to the teriflunomide group in a pooled analysis of both studies (approximately 88% in each treatment group); the most common adverse event associated with ublituximab was infusion related reactions (47.7% of patients who received ublituximab experienced at least one infusion-related reaction vs. 12.2 percent for the teriflunomide group).

ULTIMATE I & II PHASE 3 INVESTOR & ANALYST WEBCAST DETAILS

* Date & Time: Friday April 16, 2021 at 8:30 AM ET

* Key Opinion Leader Participants: Lawrence Steinman, MD, of Stanford University and the Global Study Chair for the ULTIMATE I & II Phase 3 trials Edward J. Fox, MD, PhD, of Central Texas Neurology Consultants and Chair for the ublituximab Phase 2 trial Enrique Alvarez, MD, PhD, of University of Colorado Medicine Live Webcast: http://ir.tgtherapeutics.com/events (also archived for future review) AAN ANNUAL MEETING POSTER PRESENTATION DETAILS Title: Efficacy and safety of ublituximab versus teriflunomide in relapsing multiple sclerosis: Results of the Phase 3 ULTIMATE I and II trials Date & Time: Available for viewing beginning Saturday April 17, 2021 at 8:00 AM ET Abstract Number: 4494 Lead Author: Lawrence Steinman, MD, Zimmermann Professor of Neurology & Neurological Sciences, and Pediatrics at Stanford University ABOUT THE ULTIMATE I & II TRIALS ULTIMATE I and ULTIMATE II are two 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 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). Both studies have met their primary endpoint with ublituximab treatment demonstrating a statistically significant reduction in annualized relapse rate (ARR) over a 96-week period (p<0.005 in each trial). 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. Key secondary MRI endpoints have also been met. Data from these studies are intended to support a Biologics License Application (BLA) submission for ublituximab in RMS targeted Q3 2021. Additional information on these clinical trials can be found at www.clinicaltrials.gov (NCT03277261; NCT03277248).