TG Therapeutics Completes Enrollment in the Phase 3 ENHANCE Trial Evaluating its New Simplified Dosing Schedule for BRIUMVI

Rhea-AI Summary

TG Therapeutics (NASDAQ: TGTX) announced completion of enrollment in the randomized cohort of the Phase 3 ENHANCE trial testing a consolidated Day 1/Day 15 IV dosing schedule for BRIUMVI (ublituximab) in relapsing multiple sclerosis (RMS) on Oct 28, 2025.

The trial's primary endpoint is noninferior exposure measured by AUC at Week 16. ENHANCE is randomized, double-blind and placebo-controlled and will assess pharmacokinetics, safety (including infusion-related reactions), and efficacy via T1 Gd-enhancing lesions. Dosing arms compare a single 600 mg Day 1 dose plus Day 15 placebo versus 150 mg Day 1 then 450 mg Day 15, with a 450 mg dose at Week 24.

Company commentary notes potential for a simplified regimen to improve patient convenience and infusion center efficiency and states that, if data are positive, the regimen could be ready for launch in 2027.

Positive

• Randomized Phase 3 enrollment completed in ENHANCE (Oct 28, 2025)
• Primary endpoint defined as noninferior AUC at Week 16
• Trial design is randomized, double-blind, placebo-controlled

Negative

• No efficacy or safety results reported
• Potential launch contingent on positive data; timeline not guaranteed for 2027

Insights

Clinical Development Strategist

Enrollment in the Phase 3 ENHANCE randomized cohort is complete; primary endpoint is non‑inferior AUC at week 16.

TG Therapeutics completed enrollment in the randomized arm of the ENHANCE Phase 3 trial testing a consolidated Day 1/Day 15 IV dosing schedule for BRIUMVI. The study directly measures pharmacokinetic exposure (AUC) at week 16, plus safety via infusion‑related reactions and efficacy via T1 Gd‑enhancing lesions. Two randomized arms compare a 600 mg Day 1 plus placebo Day 15 regimen against a 150 mg Day 1 then 450 mg Day 15 regimen using a Week 24 450 mg dose.

Key dependencies remain tightly factual and binary. Success depends on meeting the prespecified non‑inferiority margin for AUC at week 16 and acceptable safety results for infusion reactions and MRI lesions. Enrollment completion reduces operational risk but does not alter the trial outcome risk; results could be positive, neutral, or negative depending solely on the prespecified analyses.

Watch for the Week 16 pharmacokinetic analysis and the blinded safety/MRI readouts, and for any regulatory filing timing if the data meet non‑inferiority. Management notes a potential launch in 2027 only if data are positive, so milestone timing through 2026–2027 is the most relevant horizon.

10/28/2025 - 07:30 AM

NEW YORK, Oct. 28, 2025 (GLOBE NEWSWIRE) -- TG Therapeutics, Inc. (NASDAQ: TGTX), announced today that enrollment has completed in the randomized cohort of the Phase 3 ENHANCE trial evaluating a consolidated Day 1 and Day 15 dosing schedule for IV BRIUMVI^® (ublituximab-xiiy), the company’s novel, glycoengineered, anti-CD20 monoclonal antibody, in people with relapsing forms of multiple sclerosis (RMS). The primary endpoint of this trial is non inferior exposure with respect to area under the curve (AUC) at week 16.

BRIUMVI is currently approved in the United States, as well as several countries outside of the U.S., as a one-hour intravenous (IV) infusion administered twice a year, following the starting dose, in adults with RMS.

Michael S. Weiss, the Company's Chairman and Chief Executive Officer, stated, “We are excited to announce the completion of enrollment in the randomized cohort of the ENHANCE Phase 3 trial, which opened for enrollment last quarter. The study is designed to evaluate whether consolidating the BRIUMVI Day 1 and Day 15 infusions into a single Day 1 infusion maintains the exposure seen with our existing approved regimen. BRIUMVI’s one-hour infusion duration already offers best-in-class convenience among available IV anti-CD20s and this represents an important step toward making treatment even more convenient for patients and more efficient for infusion centers. The enthusiasm and engagement we’ve seen from both trial sites and participants in exploring this simplified dosing schedule has exceeded our expectations. We remain deeply committed to continuing to enhance the overall patient experience with BRIUMVI, and if the data are positive, this new dosing regimen could be ready for launch in 2027.”

ENHANCE Phase 3 Trial Overview
The ENHANCE Phase 3b trial is a randomized, double-blind, placebo-controlled, multicenter study designed to evaluate the pharmacokinetics, safety, and efficacy of a modified regimen of IV BRIUMVI (ublituximab) as measured by exposure (AUC), infusion-related reactions, and T1 Gadolinium (Gd)-enhancing lesions, respectively, in participants with Relapsing Multiple Sclerosis (RMS). Participants were randomized into one of two arms: 600 mg of BRIUMVI on day 1 followed by a placebo infusion on Day 15 and 450 mg BRIUMVI infusion at Week 24 or 150 mg of BRIUMVI on Day 1 followed by 450 mg on Day 15 and at Week 24. The primary endpoint of the randomized portion of the study is non inferior exposure with respect to area under the curve (AUC) at week 16.

ABOUT BRIUMVI^® (ublituximab-xiiy) 150 mg/6 mL Injection for IV
BRIUMVI is a novel monoclonal antibody that targets a unique epitope on CD20-expressing B-cells. Targeting CD20 using monoclonal antibodies has proven to be an important therapeutic approach for the management of autoimmune disorders, such as RMS. BRIUMVI is uniquely designed to lack certain sugar molecules normally expressed on the antibody. Removal of these sugar molecules, a process called glycoengineering, allows for efficient B-cell depletion at low doses.

BRIUMVI is indicated in the U.S. for the treatment of adults with RMS, including clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease and in several foreign nations for the treatment of adult patients with RMS with active disease defined by clinical or imaging features.

A list of authorized specialty distributors can be found at www.briumvi.com.

IMPORTANT SAFETY INFORMATION
Contraindications: BRIUMVI is contraindicated in patients with:

• Active Hepatitis B Virus infection
• A history of life-threatening infusion reaction to BRIUMVI

WARNINGS AND PRECAUTIONS

Infusion Reactions: BRIUMVI can cause infusion reactions, which can include pyrexia, chills, headache, influenza-like illness, tachycardia, nausea, throat irritation, erythema, and an anaphylactic reaction. In MS clinical trials, the incidence of infusion reactions in BRIUMVI-treated patients who received infusion reaction-limiting premedication prior to each infusion was 48%, with the highest incidence within 24 hours of the first infusion. 0.6% of BRIUMVI-treated patients experienced infusion reactions that were serious, some requiring hospitalization.

Observe treated patients for infusion reactions during the infusion and for at least one hour after the completion of the first two infusions unless infusion reaction and/or hypersensitivity has been observed in association with the current or any prior infusion. Inform patients that infusion reactions can occur up to 24 hours after the infusion. Administer the recommended pre-medication to reduce the frequency and severity of infusion reactions. If life-threatening, stop the infusion immediately, permanently discontinue BRIUMVI, and administer appropriate supportive treatment. Less severe infusion reactions may involve temporarily stopping the infusion, reducing the infusion rate, and/or administering symptomatic treatment.

Infections: Serious, life-threatening or fatal, bacterial and viral infections have been reported in BRIUMVI-treated patients. In MS clinical trials, the overall rate of infections in BRIUMVI-treated patients was 56% compared to 54% in teriflunomide-treated patients. The rate of serious infections was 5% compared to 3% respectively. There were 3 infection-related deaths in BRIUMVI-treated patients. The most common infections in BRIUMVI-treated patients included upper respiratory tract infection (45%) and urinary tract infection (10%). Delay BRIUMVI administration in patients with an active infection until the infection is resolved.

Consider the potential for increased immunosuppressive effects when initiating BRIUMVI after immunosuppressive therapy or initiating an immunosuppressive therapy after BRIUMVI.

Hepatitis B Virus (HBV) Reactivation: HBV reactivation occurred in an MS patient treated with BRIUMVI in clinical trials. Fulminant hepatitis, hepatic failure, and death caused by HBV reactivation have occurred in patients treated with anti-CD20 antibodies. Perform HBV screening in all patients before initiation of treatment with BRIUMVI. Do not start treatment with BRIUMVI in patients with active HBV confirmed by positive results for HB surface antigen (HBsAg) and anti-HB tests. For patients who are negative for HBsAg and positive for HB core antibody [HBcAb+] or are carriers of HBV [HBsAg+], consult a liver disease expert before starting and during treatment.

Progressive Multifocal Leukoencephalopathy (PML): Although no cases of PML have occurred in BRIUMVI-treated MS patients, JC virus infection resulting in PML has been observed in patients treated with other anti-CD20 antibodies and other MS therapies.

If PML is suspected, withhold BRIUMVI and perform an appropriate diagnostic evaluation. Typical symptoms associated with PML are diverse, progress over days to weeks, and include progressive weakness on one side of the body or clumsiness of limbs, disturbance of vision, and changes in thinking, memory, and orientation leading to confusion and personality changes.

MRI findings may be apparent before clinical signs or symptoms; monitoring for signs consistent with PML may be useful. Further investigate suspicious findings to allow for an early diagnosis of PML, if present. Following discontinuation of another MS medication associated with PML, lower PML-related mortality and morbidity have been reported in patients who were initially asymptomatic at diagnosis compared to patients who had characteristic clinical signs and symptoms at diagnosis.

If PML is confirmed, treatment with BRIUMVI should be discontinued.

Vaccinations: Administer all immunizations according to immunization guidelines: for live or live-attenuated vaccines, at least 4 weeks and, whenever possible, at least 2 weeks prior to initiation of BRIUMVI for non-live vaccines. BRIUMVI may interfere with the effectiveness of non-live vaccines. The safety of immunization with live or live-attenuated vaccines during or following administration of BRIUMVI has not been studied. Vaccination with live virus vaccines is not recommended during treatment and until B-cell repletion.

Vaccination of Infants Born to Mothers Treated with BRIUMVI During Pregnancy: In infants of mothers exposed to BRIUMVI during pregnancy, assess B-cell counts prior to administration of live or live-attenuated vaccines as measured by CD19⁺ B-cells. Depletion of B-cells in these infants may increase the risks from live or live-attenuated vaccines. Inactivated or non-live vaccines may be administered prior to B-cell recovery. Assessment of vaccine immune responses, including consultation with a qualified specialist, should be considered to determine whether a protective immune response was mounted.

Fetal Risk: Based on data from animal studies, BRIUMVI may cause fetal harm when administered to a pregnant woman. Transient peripheral B-cell depletion and lymphocytopenia have been reported in infants born to mothers exposed to other anti-CD20 B-cell depleting antibodies during pregnancy. Advise females of reproductive potential to use effective contraception during BRIUMVI treatment and for 6 months after the last dose.

Reduction in Immunoglobulins: As expected with any B-cell depleting therapy, decreased immunoglobulin levels were observed. Decrease in immunoglobulin M (IgM) was reported in 0.6% of BRIUMVI-treated patients compared to none of the patients treated with teriflunomide in RMS clinical trials. Monitor the levels of quantitative serum immunoglobulins during treatment, especially in patients with opportunistic or recurrent infections, and after discontinuation of therapy, until B-cell repletion. Consider discontinuing BRIUMVI therapy if a patient with low immunoglobulins develops a serious opportunistic infection or recurrent infections, or if prolonged hypogammaglobulinemia requires treatment with intravenous immunoglobulins.

Liver Injury: Clinically significant liver injury, without findings of viral hepatitis, has been reported in the postmarketing setting in patients treated with anti-CD20 B-cell depleting therapies approved for the treatment of MS, including BRIUMVI. Signs of liver injury, including markedly elevated serum hepatic enzymes with elevated total bilirubin, have occurred from weeks to months after administration.

Patients treated with BRIUMVI found to have an alanine aminotransaminase (ALT) or aspartate aminotransferase (AST) greater than 3x the upper limit of normal (ULN) with serum total bilirubin greater than 2x ULN are potentially at risk for severe drug-induced liver injury.

Obtain liver function tests prior to initiating treatment with BRIUMVI, and monitor for signs and symptoms of any hepatic injury during treatment. Measure serum aminotransferases, alkaline phosphatase, and bilirubin levels promptly in patients who report symptoms that may indicate liver injury, including new or worsening fatigue, anorexia, nausea, vomiting, right upper abdominal discomfort, dark urine, or jaundice. If liver injury is present and an alternative etiology is not identified, discontinue BRIUMVI.

Most Common Adverse Reactions: The most common adverse reactions in RMS trials (incidence of at least 10%) were infusion reactions and upper respiratory tract infections.

Physicians, pharmacists, or other healthcare professionals with questions about BRIUMVI should visit www.briumvi.com.

The full Summary of Product Characteristics approved in the European Union (EU) for BRIUMVI can be found here Briumvi | European Medicines Agency (europa.eu).

ABOUT BRIUMVI PATIENT SUPPORT in the U.S.
BRIUMVI Patient Support is a flexible program designed by TG Therapeutics to support U.S. patients through their treatment journey in a way that works best for them. More information about the BRIUMVI Patient Support program can be accessed at www.briumvipatientsupport.com.

ABOUT MULTIPLE SCLEROSIS
Relapsing multiple sclerosis (RMS) is a chronic demyelinating disease of the central nervous system (CNS) and includes people with relapsing-remitting multiple sclerosis (RRMS) and people with secondary progressive multiple sclerosis (SPMS) who continue to experience relapses. RRMS is the most common form of multiple sclerosis (MS) and is characterized by episodes of new or worsening signs or symptoms (relapses) followed by periods of recovery. It is estimated that nearly 1 million people are living with MS in the United States and approximately 85% are initially diagnosed with RRMS.^1,2 The majority of people who are diagnosed with RRMS will eventually transition to SPMS, in which they experience steadily worsening disability over time. Worldwide, more than 2.3 million people have a diagnosis of MS.¹

ABOUT TG THERAPEUTICS
TG Therapeutics is a fully integrated, commercial stage, biopharmaceutical company focused on the acquisition, development and commercialization of novel treatments for B-cell diseases. In addition to a research pipeline including several investigational medicines, TG Therapeutics has received approval from the U.S. Food and Drug Administration (FDA) for BRIUMVI^® (ublituximab-xiiy) for the treatment of adult patients with relapsing forms of multiple sclerosis, including clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease, as well as approval by several foreign nations for BRIUMVI to treat adult patients with RMS who have active disease defined by clinical or imaging features. For more information, visit www.tgtherapeutics.com, and follow us on X (formerly Twitter) @TGTherapeutics and on LinkedIn.

BRIUMVI^® is a registered trademark of TG Therapeutics, Inc.

Cautionary Statement
This press release contains forward-looking statements that involve a number of risks and uncertainties. For those statements, we claim the protection of the safe harbor for forward-looking statements contained in the Private Securities Litigation Reform Act of 1995.

Any forward-looking statements in this press release are based on management's current expectations and beliefs and are subject to a number of risks, uncertainties and important factors that may cause actual events or results to differ materially from those expressed or implied by any forward-looking statements contained in this press release. In addition to the risk factors identified from time to time in our reports filed with the U.S. Securities and Exchange Commission (SEC), factors that could cause our actual results to differ materially include the below.

Such forward looking statements include but are not limited to statements regarding expectations for the timing and success of the commercialization and availability of BRIUMVI^® (ublituximab-xiiy) for RMS in the United States, or any jurisdictions outside of the United States; anticipated healthcare professional (HCP) and patient acceptance and use of BRIUMVI for the approved indications; expectations of future revenue for BRIUMVI, or TG expenses or profit estimates or targets; expectations and timing for our subcutaneous BRIUMVI program, including feasibility, approvability and commercial acceptance, expectations and timing for our ENHANCE Phase 3 trial combining day 1 and day 15 doses, including, feasibility, approvability and commercial acceptance and impact on BRIUMVI sales.

Additional factors that could cause our actual results to differ materially include the following: the Company’s ability to continue to commercialize BRIUMVI; the risk that trends in prescriptions are not maintained or that prescriptions are not filled; the failure to obtain and maintain payor coverage; the risk that HCP interest in BRIUMVI will not be sustained; the risk that momentum in sales for BRIUMVI will not be sustained during the course of the year; the risk that the commercialization of BRIUMVI does not continue to exceed expectations; the risk that our BRIUMVI revenue targets will not be achieved; the failure to obtain and maintain requisite regulatory approvals, including the risk that the Company fails to satisfy post-approval regulatory requirements, the potential for variations from the Company’s projections and estimates about the potential market for BRIUMVI due to a number of factors, including, further limitations that regulators may impose on the required labeling for BRIUMVI (such as modifications, resulting from safety signals that arise in the post-marketing setting or in the long-term extension study from the ULTIMATE I and II clinical trials); the Company’s ability to meet post-approval compliance obligations (on topics including but not limited to product quality, product distribution and supply chain, pharmacovigilance, and sales and marketing); the Company’s reliance on third parties for manufacturing, distribution and supply, and other support functions for our clinical and commercial products, including BRIUMVI, and the ability of the Company and its manufacturers and suppliers to produce and deliver BRIUMVI to meet the market demand for BRIUMVI; ; the risk that any individual patient’s clinical experience in the post-marketing setting, or the aggregate patient experience in the post-marketing setting, may differ from that demonstrated in controlled clinical trials such as ULTIMATE I and II; the risk that the Company does not achieve its 2025 development pipeline anticipated milestones or goals in the timeframe projected or at all, including completing a pivotal program based on data from the ENHANCE trial to consolidate day 1 and day 15 dosing; the risk that the ENHANCE Phase 3 trial will not be successful or if successful will not be approved by the FDA or achieve commercial acceptance; the uncertainties generally inherent in research and development; regulatory developments, legislative actions, executive orders, including the imposition of tariffs and policy changes in the U.S. and other jurisdictions; and general political, economic and business conditions. Further discussion about these and other risks and uncertainties can be found in our Annual Report on Form 10-K for the fiscal year ended December 31, 2024 and in our other filings with the SEC.

Any forward-looking statements set forth in this press release speak only as of the date of this press release. We do not undertake to update any of these forward-looking statements to reflect events or circumstances that occur after the date hereof. This press release and prior releases are available at www.tgtherapeutics.com. The information found on our website is not incorporated by reference into this press release and is included for reference purposes only.

CONTACT:
	Investor Relations
	Email: ir@tgtxinc.com
	Telephone: 1.877.575.TGTX (8489), Option 4
	Media Relations
	Email: media@tgtxinc.com
	Telephone: 1.877.575.TGTX (8489), Option 6

^{1. MS Prevalence. National Multiple Sclerosis Society website. https://www.nationalmssociety.org/About-the-Society/MS-Prevalence. Accessed October 26, 2020. 2. Multiple Sclerosis International Federation, 2013 via Datamonitor p. 236.}

FAQ

What did TG Therapeutics announce about the ENHANCE Phase 3 trial on Oct 28, 2025?

TG Therapeutics announced completion of enrollment in the randomized cohort of the ENHANCE Phase 3 trial evaluating a consolidated Day 1/Day 15 IV dosing schedule for BRIUMVI.

What is the primary endpoint of the ENHANCE Phase 3 trial (TGTX)?

The primary endpoint is noninferior exposure measured by AUC at Week 16 in the randomized portion of the trial.

How are the dosing arms structured in the ENHANCE randomized cohort?

One arm receives 600 mg on Day 1 plus placebo on Day 15 and 450 mg at Week 24; the other receives 150 mg Day 1, 450 mg Day 15, and 450 mg at Week 24.

Will the simplified BRIUMVI dosing be available in 2027 if ENHANCE is positive?

The company said that if the data are positive, the simplified dosing regimen could be ready for launch in 2027, but that timeline is conditional on results and regulatory steps.

What outcomes besides AUC will ENHANCE assess for BRIUMVI?

ENHANCE will also evaluate safety including infusion-related reactions and T1 Gd-enhancing lesions as efficacy measures.

Is BRIUMVI currently approved and how is it administered today?

BRIUMVI is approved in the U.S. and several other countries as a one-hour IV infusion given twice yearly following the starting dose for adults with relapsing multiple sclerosis.