ULTRA-V Phase 2 trial has reached completion of patient enrollment

NEW YORK, April 21, 2021 (GLOBE NEWSWIRE) -- TG Therapeutics, Inc. (NASDAQ: TGTX), today announced the initiation of patient enrollment into the ULTRA-V Phase 3 randomized trial, evaluating the time-limited triple combination of UKONIQ™ (umbralisib), the Company’s once-daily, inhibitor of PI3K-delta and CK1-epsilon, ublituximab, the Company’s investigational glycoengineered anti-CD20 monoclonal antibody, and venetoclax, compared to the continuous doublet combination of UKONIQ plus ublituximab (U2) in patients with both frontline and relapsed or refractory chronic lymphocytic leukemia (CLL). The primary endpoint for the ULTRA-V Phase 3 trial is Progression-free Survival (PFS), and the trial is designed support the full approval of the triple combination of U2 plus venetoclax.

The Company also announced completion of enrollment into the ULTRA-V Phase 2 global, single arm trial evaluating the triple combination of U2 plus venetoclax. This primary endpoint for this trial is overall response rate (ORR) and complete response (CR) rate, and the trial completed enrollment with approximately 165 patients enrolled. The trial enrolled patients with front line CLL, as well as relapsed or refractory CLL, including patients who were refractory to prior Bruton’s Kinase Inhibitor (BTK) therapy.

Richard R. Furman, MD, Director of CLL Research Center at Weill Cornell Medicine and Study Chair for the ULTRA-V Phase 2 and Phase 3 trials stated, “We are excited to launch this pivotal Phase 3 study based on the promising Phase 1 clinical results reported to date on the triplet combination of UKONIQ, ublituximab and venetoclax in patients with CLL. While recent approvals provide excellent treatment options for patients, disease progression and treatment tolerability still remain problematic for many patients. Our belief is that time-limited treatment regimens, such as U2 plus venetoclax, have the potential to produce meaningful responses without the need to expose patients to continuous therapy and related toxicities. We look forward to presenting the results of the Phase 2 portion of this study at a future medical meeting. I want to thank my colleagues for their strong support of the Phase 2 ULTRA-V trial and look forward to continuing and expanding our efforts now in Phase 3.”

Michael S. Weiss, Executive Chairman and Chief Executive Officer of TG Therapeutics stated, “We are extremely pleased with the rapid enrollment seen in the ULTRA-V Phase 2 trial, with approximately 165 patients enrolled in approximately 16 months throughout a limited number of U.S. trial sites, with the majority of the enrollment taking place in 2020 during the height of the COVID-19 pandemic. We are further encouraged by the strong interest of new trial sites to participate in the Phase 3 portion of the trial. We believe the encouraging early results observed in the Phase 1 trial of U2 plus venetoclax, led by Dr. Paul Barr at the University of Rochester, which were most recently presented at the ASH annual meeting in 2020, are supportive of our decision to quickly initiate the ULTRA-V Phase 2 and 3 trials. We look forward to providing an update from the Phase 1 trial later this year and initial results from the Phase 2 portion of the ULTRA-V trial in 2022.”ABOUT ULTRA-V PHASE 3 TRIAL The ULTRA-V Phase 3 trial is an open-label, multicenter, randomized controlled clinical trial comparing the time-limited triple combination of UKONIQ and ublituximab (U2) plus venetoclax, to an active control arm of continuous U2. The Phase 3 trial includes two independent randomized cohorts of CLL subjects: a treatment-naïve cohort and a previously treated cohort, with each cohort being enrolled and evaluated independently of each other. The primary endpoint for the trial is Progression-free Survival (PFS). This trial is being led by Richard R. Furman, MD, Director of CLL Research Center at Weill Cornell Medicine and targeting over 60 U.S. trial sites.ABOUT ULTRA-V PHASE 2 TRIAL The ULTRA-V Phase 2 trial, (NCT03801525), is an open-label, multicenter, trial designed to investigate the efficacy and safety of ublituximab and UKONIQ combined with venetoclax in subjects with CLL. The primary endpoint of the trial is overall response rate (ORR) and Complete Response (CR) rate. The trial enrolled approximately 165 patients with front line and previously treated CLL at 26 sites throughout the United States.

ABOUT U2 PLUS VENETOCLAX PHASE 1 TRIAL The Phase 1/2 trial, (NCT03379051), is a multi-center, dose-escalation trial designed to assess the safety and efficacy of U2 plus venetoclax in patients with relapsed or refractory CLL. The primary objective of the trial is to evaluate the safety of venetoclax after U2 induction. The secondary objectives are clinical efficacy as defined by ORR (including CR rate), PFS, and undetectable minimal residual disease (MRD) rate after 12 cycles of therapy. The trial enrolled approximately 50 CLL patients, and interim results were most recently presented on 43 CLL patients at the American Society of Hematology (ASH) annual meeting in December 2020. ABOUT CHRONIC LYMPHOCYTIC LEUKEMIAChronic lymphocytic leukemia (CLL) is the most common type of adult leukemia. It is estimated there will be more than 20,000 new cases of CLL diagnosed in the United States in 2020 and approximately 45,000 new cases globally in 2020.1,2 Although signs and symptoms of CLL may disappear for a period of time after initial treatment, the disease is considered incurable and many people will require additional treatment due to the return of malignant cells.

ABOUT TG THERAPEUTICS, INC. TG Therapeutics is a fully-integrated, commercial stage biopharmaceutical company focused on the acquisition, development and commercialization 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 two programs 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 www.tgtherapeutics.com, and follow us on Twitter @TGTherapeutics and Linkedin.UKONIQ™ is a trademark of TG Therapeutics, Inc.

ABOUT UKONIQ™ (umbralisib) UKONIQ is the first and only oral inhibitor of phosphoinositide 3 kinase (PI3K) delta and casein kinase 1 (CK1) epsilon. PI3K-delta is known to play an important role in supporting cell proliferation and survival, cell differentiation, intercellular trafficking and immunity and is expressed in both normal and malignant B-cells. CK1-epsilon is a regulator of oncoprotein translation and has been implicated in the pathogenesis of cancer cells, including lymphoid malignancies. 

UKONIQ is indicated for the treatment of adult patients with relapsed or refractory marginal zone lymphoma (MZL) who have received at least one prior anti-CD20-based regimen and for the treatment of adult patients with relapsed or refractory follicular lymphoma (FL) who have received at least three prior lines of systemic therapy.

These indications are approved under accelerated approval based on overall response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.

IMPORANT SAFETY INFORMATIONInfections: Serious, including fatal, infections occurred in patients treated with UKONIQ. Grade 3 or higher infections occurred in 10% of 335 patients, with fatal infections occurring in