TG Therapeutics Announces Two Publications Highlighting BRIUMVI in Medical Journals

Rhea-AI Summary

TG Therapeutics (NASDAQ: TGTX) has announced the publication of two significant journal articles focusing on BRIUMVI® (ublituximab-xiiy) in multiple sclerosis (MS) treatment. The first publication in Frontiers in Immunology presents a case series of seven MS patients who switched to BRIUMVI from other anti-CD20 therapies due to efficacy or tolerability issues.

The second article, published in CNS DRUGS, examines the evolution of anti-CD20 treatments for MS, discussing key characteristics such as scaffold, mechanism of action, and Fc engineering that may influence therapeutic efficacy and patient experience.

Michael S. Weiss, Executive Chairman and CEO, emphasized these publications provide rationale for switching patients within the CD20 class before abandoning it entirely. The company continues to study this phenomenon through their ongoing ENHANCE and ENABLE studies to further validate these initial findings.

Positive

• Publication of clinical evidence supporting BRIUMVI as viable alternative within CD20 class
• Real-world data showing successful patient transitions to BRIUMVI
• Ongoing clinical studies (ENHANCE and ENABLE) to further validate initial findings

Negative

• sample size of only seven patients in the switch study
• Results are currently only anecdotal and require further validation

Insights

Biotechnology Analyst

TG Therapeutics' announcement of two publications highlighting BRIUMVI (ublituximab-xiiy) represents a strategic positioning effort for their multiple sclerosis treatment within the competitive anti-CD20 class. The publications serve dual purposes: establishing a scientific rationale for switching patients between anti-CD20 therapies and providing initial clinical evidence supporting this approach.

The case series documenting seven patients who switched to BRIUMVI from other anti-CD20 therapies offers preliminary real-world evidence of potential benefits for patients experiencing efficacy or tolerability issues with existing treatments. While the sample size is very small, these early findings could influence prescriber perceptions and decision-making processes.

The second publication exploring the evolution of anti-CD20 treatments provides scientific context for BRIUMVI's potential differentiation, focusing on its unique characteristics including scaffold design, mechanism of action, and Fc engineering. These differences might explain improvements in B-cell depletion efficacy, reduced infusion reactions, and elimination of certain pharmacogenetic effects.

The company is strategically positioning BRIUMVI as a viable alternative within the same therapeutic class rather than forcing patients to abandon anti-CD20 therapy entirely when experiencing issues. This "switch before class change" approach potentially expands BRIUMVI's addressable market to include patients currently on competing anti-CD20 therapies who are experiencing suboptimal responses.

The ongoing ENHANCE and ENABLE studies mentioned will be critical in determining whether these anecdotal benefits translate to reproducible advantages in larger patient populations, which would substantiate the early findings highlighted in these publications.

Medical Research Specialist

These publications represent an incremental step in establishing BRIUMVI's clinical profile and potential advantages within the anti-CD20 therapeutic landscape for multiple sclerosis. The case series, while to just seven patients, provides valuable initial insights into real-world outcomes when switching patients from other anti-CD20 therapies to ublituximab.

The mechanistic differences highlighted in the CNS DRUGS publication are particularly noteworthy. The focus on scaffold structure, preferential antibody-dependent cellular cytotoxicity (ADCC) versus complement-dependent cytotoxicity (CDC), and Fc engineering speaks to potential molecular advantages that could translate to clinical benefits, including more complete B-cell depletion and reduced infusion reactions.

From a clinical perspective, the "within-class switching" approach addressed by these publications aligns with practical treatment considerations. Physicians typically prefer keeping patients within a mechanism of action that has shown some benefit rather than completely abandoning it, especially for complex diseases like MS where predictive biomarkers for treatment response remain

However, these publications should be viewed as hypothesis-generating rather than definitive evidence. The retrospective nature of the case series and the inherent selection bias in such reports necessitates caution in interpretation. The ultimate clinical positioning of BRIUMVI will depend on the results from the company's ongoing ENHANCE and ENABLE studies, which should provide more robust data on the benefits of switching between anti-CD20 therapies.

These publications effectively establish a scientific and clinical framework for BRIUMVI's potential differentiation, but larger, prospective studies with appropriate controls will be necessary to substantiate these preliminary findings and influence treatment guidelines.

NEW YORK, April 07, 2025 (GLOBE NEWSWIRE) -- TG Therapeutics, Inc. (NASDAQ: TGTX) today announced the publication of two journal articles one describing the evolution of CD20 treatments for multiple sclerosis (MS) and the other detailing the experience of seven individuals with MS who switched to BRIUMVI® (ublituximab-xiiy) from a different anti-CD20 monoclonal antibody therapy due to efficacy or tolerability concerns. Details of the publications are provided below.

Michael S. Weiss, the Company’s Executive Chairman and Chief Executive Officer stated, "We are encouraged by these publications, and believe taken together they may provide a rationale for switching patients within the CD20 class prior to leaving the class, as well as the first anecdotal evidence of the success of such a strategy, as highlighted by the seven case reports in Frontiers in Immunology. The findings reinforce the potential of BRIUMVI in improving patient outcomes for those seeking an alternative to their previous anti-CD20 therapy. Furthermore, the article in CNS DRUGS offers an insightful look at the evolution of anti-CD20 treatments and a potential rationale as to why switching within the same class is a viable strategy. We remain committed to the MS community and believe these papers highlight the real-world impact BRIUMVI can have on the those living with MS and we will continue to study this phenomenon through our ongoing ENHANCE and ENABLE studies to assess if these anecdotal accounts can be further supported.”  

JOURNAL ARTICLES:
Title: Switching to Ublituximab from Prior anti-CD20 Monoclonal Antibody Therapy: A Case Report Series

• The article describes a retrospective case series of seven individuals with multiple sclerosis (MS) treated in private practice or at an MS clinic who switched to ublituximab from a different anti-CD20 monoclonal antibody therapy due to efficacy or tolerability concerns. Details of each case, including clinical and/or radiological outcomes on initial anti-CD20 therapy, reasons for switching, and outcomes after starting ublituximab therapy are provided.
• This case series was published in Frontiers in Immunology and the online version of the publication can be accessed at Frontiers in Immunology.
  

Title: The Evolution of Anti-CD20 Treatment for Multiple Sclerosis

• The article focuses on the unique characteristics of the anti-CD20 monoclonal antibodies used to treat MS that may be relevant to differences in therapeutic efficacy, tolerability, and patient experience—namely, scaffold, mechanism of action (eg, complement-dependent cytotoxicity vs antibody-dependent cellular cytotoxicity), and Fc engineering. The discussion of these refinements includes improving the extent of B-cell depletion, reducing infusion-related reactions, and eliminating pharmacogenetic effects of FcγRIIIa polymorphisms.
• This article was published in CNS DRUGS, a division of Adis International (Spring Nature) and the online version of the article can be accessed at CNS DRUGS.

ABOUT THE ULTIMATE I & II PHASE 3 TRIALS
ULTIMATE I & II are two randomized, double-blind, double-dummy, parallel group, active comparator-controlled clinical trials of identical design, in patients with RMS treated for 96 weeks. Patients were randomized to receive either BRIUMVI, given as an IV infusion of 150 mg administered in four hours, 450 mg two weeks after the first infusion administered in one hour, and 450 mg every 24 weeks administered in one hour, with oral placebo administered daily; or teriflunomide, the active comparator, given orally as a 14 mg daily dose with IV placebo administered on the same schedule as BRIUMVI. Both studies enrolled patients who had experienced at least one relapse in the previous year, two relapses in the previous two years, or had the presence of a T1 gadolinium (Gd)-enhancing lesion in the previous year. Patients were also required to have an Expanded Disability Status Scale (EDSS) score from 0 to 5.5 at baseline. 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. Additional information on these clinical trials can be found at www.clinicaltrials.gov (NCT03277261; NCT03277248).

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 for the treatment of adults with relapsing forms of multiple sclerosis (RMS), to include clinically isolated syndrome, relapsing- remitting disease, and active secondary progressive disease.

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, JCV 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. A pregnancy test is recommended in females of reproductive potential prior to each infusion. 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.

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.

ABOUT BRIUMVI PATIENT SUPPORT
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 has received U.S. Food and Drug Administration (FDA) approval for BRIUMVI® (ublituximab-xiiy), for the treatment of adult patients with relapsing forms of multiple sclerosis (RMS), to include clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease, as well as approval by the European Commission (EC) and the Medicines and Healthcare Products Regulatory Agency (MHRA) for BRIUMVI to treat adult patients with RMS who have active disease defined by clinical or imaging features in Europe and the United Kingdom, respectively. 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 the results of the ULTIMATE I & II Phase 3 studies, the ENHANCE Phase 3b study, and BRIUMVI as a treatment for relapsing forms of multiple sclerosis (RMS). Additional factors that could cause our actual results to differ materially include the following: the risk that the data from the ULTIMATE I & II or ENHANCE trials that we announce or publish may change, or the product profile of BRIUMVI may be impacted, as more data or additional endpoints are analyzed; the risk that data may emerge from future clinical studies or from adverse event reporting that may affect the safety and tolerability profile and commercial potential of BRIUMVI; the risk that any individual or series of 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 BRIUMVI will not be commercially successful; our ability to expand our commercial infrastructure, and successfully market and sell BRIUMVI in RMS; the Company’s reliance on third parties for manufacturing, distribution and supply, and a range of other support functions for our commercial and clinical 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 failure to obtain and maintain requisite regulatory approvals, including the risk that the Company fails to satisfy post-approval regulatory requirements and general political, economic and business. 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 U.S. Securities and Exchange Commission.

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 are the key findings from the BRIUMVI switch study published in Frontiers in Immunology?

The study documented seven MS patients who successfully switched to BRIUMVI from other anti-CD20 therapies due to efficacy or tolerability concerns, providing initial evidence for the viability of within-class switching.

How does BRIUMVI (TGTX) differ from other anti-CD20 MS treatments according to the CNS DRUGS publication?

The article discusses BRIUMVI's unique characteristics in scaffold, mechanism of action (complement-dependent vs antibody-dependent cellular cytotoxicity), and Fc engineering, which may affect efficacy and tolerability.

What ongoing studies is TG Therapeutics conducting to validate BRIUMVI's effectiveness?

TG Therapeutics is conducting the ENHANCE and ENABLE studies to further validate the initial findings of successful patient switching to BRIUMVI.

What potential benefits does BRIUMVI offer for MS patients according to the publications?

BRIUMVI may offer improved outcomes for patients seeking alternatives to previous anti-CD20 therapy, with potential benefits in B-cell depletion, reduced infusion reactions, and elimination of pharmacogenetic effects.