TG Therapeutics Highlights Seven-Year BRIUMVI Data, Positive Phase 3 ENHANCE Results and Progress in Progressive MS Research at MSToronto2026
TG Therapeutics, Inc. (NASDAQ: TGTX) has announced a series of updated clinical and real-world data presentations at MSToronto2026, the 10th Joint ACTRIMS-ECTRIMS Meeting, highlighting the long-term safety and efficacy of BRIUMVI® (ublituximab-xiiy), advances in subcutaneous administration, and continued research into treatment options for multiple sclerosis (MS).
The presentations include seven-year follow-up results from the ULTIMATE I and II trials, Phase 1 pharmacokinetic and pharmacodynamic findings for subcutaneous BRIUMVI, Phase 3 ENHANCE trial results, and updated findings from the Phase 4 ENABLE real-world study. Additional presentations examine outcomes among patients transitioning from other anti-CD20 therapies, changes in immune cell populations, genetic diversity in MS, and real-world treatment experience in Europe.
The company also announced that the abstract for a late-breaking oral presentation is now available, outlining initial results from the Phase 1 TG-Azercel-101 study evaluating azer-cel, an allogeneic CD19-directed chimeric antigen receptor (CAR) T-cell therapy, in patients with primary progressive multiple sclerosis (PPMS).
According to TG Therapeutics, the latest findings strengthen the evidence supporting BRIUMVI as a treatment option for relapsing forms of MS while highlighting potential improvements in treatment initiation, administration flexibility, and patient experience. The results also contribute to the company’s efforts to expand its anti-CD20 treatment franchise and explore emerging therapeutic approaches for progressive MS.
Seven-Year ULTIMATE I and II Results Demonstrate Sustained BRIUMVI Treatment Outcomes
One of the key presentations at MSToronto2026 focuses on seven-year safety and efficacy outcomes from the ULTIMATE I and II clinical trials and their long-term follow-up.
The findings indicate that patients who continuously received BRIUMVI maintained sustained disease control over seven years of treatment. The annualized relapse rate (ARR) was 0.018 at Year 7, indicating a low reported frequency of relapses in the continuously treated population.
The analysis also evaluated confirmed disability progression, an important measure in MS research because the disease can cause progressive neurological impairment that affects mobility, coordination, and other functions.
At seven years, 88.3% of patients who continuously received BRIUMVI remained free from 24-week confirmed disability progression. Conversely, 11.7% experienced confirmed disability progression.
Among patients who initially received teriflunomide before switching to BRIUMVI, 17.4% experienced confirmed disability progression. The difference between the groups was statistically significant, with a reported p-value of 0.0148.
The findings suggest that continuous BRIUMVI treatment was associated with favorable long-term disability outcomes compared with the treatment sequence involving initial teriflunomide therapy followed by a switch to BRIUMVI. However, the results should be interpreted in the context of the study design and the characteristics of the patients included in the long-term analysis.
The analysis also examined confirmed disability improvement. Among patients continuously treated with BRIUMVI, 17.6% achieved confirmed disability improvement, compared with 13.6% of patients in the switch group. The difference was reported with a p-value of 0.0492.
These outcomes are relevant because treatment goals in relapsing MS extend beyond reducing relapses to include preventing disability accumulation and preserving neurological function over time.
The long-term safety analysis found that BRIUMVI’s safety profile remained consistent through seven years of treatment, with no apparent increase in exposure-adjusted adverse event rates over time. This finding adds to the company’s long-term evidence base concerning the tolerability of ublituximab in patients with relapsing MS.
The seven-year results are available in the presentation titled Seven-Year Safety and Efficacy Outcomes for Ublituximab Treatment in Relapsing MS.
Phase 1 Subcutaneous BRIUMVI Data Support Quarterly Dosing Development
TG Therapeutics is also advancing a subcutaneous formulation of BRIUMVI, with the objective of providing an alternative administration method to the currently approved intravenous formulation.
The Phase 1 presentation, titled Pharmacokinetic/Pharmacodynamic Evaluation of Ublituximab in Patients With Autoimmune Diseases, reports mean bioavailability of greater than 60% for subcutaneous BRIUMVI relative to intravenous administration.
Bioavailability measures the proportion of an administered drug that reaches systemic circulation. Pharmacokinetic data, which describe how a drug is absorbed and distributed in the body, help researchers determine whether different administration methods can produce suitable drug exposure.
The company used the Phase 1 bioavailability findings to inform pharmacokinetic modeling and simulation. According to TG Therapeutics, the resulting analyses support the quarterly subcutaneous dosing regimen being evaluated in a fully enrolled Phase 3 clinical trial.
The development of a subcutaneous formulation could potentially expand treatment choices for patients with relapsing MS and provide an alternative to intravenous administration. The eventual clinical role of the formulation will depend on the results of further studies, including the assessment of safety, drug exposure, and efficacy under the proposed dosing schedule.
The Phase 1 findings are available in the pharmacokinetic and pharmacodynamic presentation.
Phase 3 ENHANCE Trial Supports a Simplified Intravenous Initiation Regimen
Another major presentation at MSToronto2026 highlights results from the Phase 3 ENHANCE trial, which evaluated a consolidated initial dosing regimen for intravenous BRIUMVI.
Under the currently approved initiation schedule described in the announcement, patients receive a 150 mg infusion on Day 1 followed by a 450 mg infusion on Day 15. The ENHANCE trial evaluated whether a single 600 mg infusion on Day 1 could provide drug exposure bioequivalent to the conventional initiation regimen.
According to TG Therapeutics, the trial met its primary endpoint, demonstrating bioequivalent drug exposure between the two regimens.
The consolidated regimen could eliminate the need for a separate Day 15 infusion during treatment initiation. If supported by applicable regulatory review and authorization, this approach could reduce the number of initial infusion visits required by patients and simplify the early treatment process.
The trial also evaluated infusion-related reactions (IRRs), which are important safety considerations for intravenous antibody therapies. TG Therapeutics reported that IRRs were comparable between the treatment regimens and lower than those reported in the ULTIMATE studies. No Grade 3 or higher IRRs occurred in any participant in the ENHANCE analysis described in the announcement.
These findings support further consideration of a simplified initiation schedule, although the primary endpoint of bioequivalence does not independently establish that every clinical outcome is identical between regimens. The overall benefit-risk profile and any changes to approved administration instructions remain subject to the relevant clinical and regulatory requirements.
The findings are available in the ENHANCE consolidated dosing presentation.
ENABLE Real-World Study Reports Low Relapse Rates and Consistent Infusion Experience
TG Therapeutics also presented updated findings from ENABLE, a Phase 4 observational study evaluating the safety and effectiveness of BRIUMVI in routine clinical practice among patients with relapsing MS.
The updated analysis included 1,076 participants. During BRIUMVI treatment, 99.2% remained relapse-free, while the annualized relapse rate was 0.014.
These real-world findings complement evidence from controlled clinical trials by examining treatment experience in a broader clinical setting. Observational studies can provide useful information about treatment use, tolerability, and outcomes outside the more structured conditions of randomized trials, although differences in patient characteristics and study methods must be considered when interpreting results.
The ENABLE analysis also assessed infusion-related reactions. First-dose infusion-related reactions occurred in 18.8% of participants, a rate reported by the company as lower than that observed in the ULTIMATE studies.
Median infusion times for the second, third, and fourth infusions were 63 minutes. According to TG Therapeutics, these findings support the consistency of an approximately one-hour infusion experience in routine practice.
The results may be relevant for patients and healthcare providers considering treatment logistics, including the time required for infusion appointments and the management of treatment-related reactions.
The updated findings are available in the ENABLE Phase 4 observational study presentation.
ENHANCE Data Examine Patients Switching From Ocrelizumab
Additional ENHANCE analyses examined patients transitioning to BRIUMVI from ocrelizumab and evaluated treatment-related symptoms, B-cell depletion, and patient satisfaction.
One presentation focused on the wearing-off effect, in which patients experience a perceived reduction in treatment benefit or a return of symptoms toward the end of a dosing interval.
Among participants who reported wearing-off while receiving ocrelizumab, switching to BRIUMVI was associated with a 69% reduction in reported wearing-off at Week 24. The reduction was sustained through Week 48.
The analysis also examined B-cell depletion, an important pharmacodynamic measure for anti-CD20 therapies, which target B cells involved in immune system activity. Among participants who were not B-cell depleted when switching from a previous anti-CD20 antibody, 100% achieved B-cell depletion at Week 24 following BRIUMVI treatment, and 92.6% remained depleted at Week 48.
Patient-reported outcomes provided additional information about treatment experience. At least 98% of respondents gave positive ratings for convenience and ease of use at both Week 24 and Week 48.
These findings provide insight into the experiences of patients transitioning between anti-CD20 therapies. However, the reported associations do not establish that switching to BRIUMVI will reduce wearing-off symptoms for every patient, and individual outcomes may vary.
The presentation is available through the ENHANCE switching analysis.
Exploratory Immune Analysis Investigates Potential Biological Mechanisms
A separate exploratory analysis examined changes in immune cell populations following the transition from ocrelizumab to BRIUMVI.
The analysis included 20 participants and evaluated regulatory T cells, commonly known as Tregs, and inflammatory monocytes. Regulatory T cells contribute to immune regulation, while inflammatory monocytes can participate in inflammatory processes.
At Week 12, BRIUMVI treatment was associated with increased regulatory T cells and decreased inflammatory monocytes among the participants evaluated.
The investigators suggested that these changes may indicate a shift toward a more anti-inflammatory immune profile. The findings also offer a potential biological explanation for the reported improvements in wearing-off symptoms, despite sustained peripheral B-cell depletion.
Treatment satisfaction was high among participants both with and without wearing-off symptoms at baseline.
Because this was a small exploratory analysis, the results should be considered preliminary. Further research will be necessary to establish whether the observed immune changes are directly related to symptom improvements and whether they have broader clinical significance.
The findings are detailed in the ENHANCE immunophenotyping presentation.
Genetic Diversity Study Examines Fc-Receptor Variants in Multiple Sclerosis
TG Therapeutics also highlighted a pilot study investigating Fc biology and genetic diversity among people with MS.
The multicenter analysis included 349 people with MS and 38 control participants. Researchers identified differences in Fc-receptor and immunoglobulin G1 (IgG1) genetic variants across racial groups, including variants that may be relevant to antibody binding and recycling.
Fc receptors interact with the constant region of antibodies and can influence immune system functions. Genetic differences affecting these interactions may be relevant to understanding variation in responses to monoclonal antibody therapies.
The findings are preliminary and do not establish that particular genetic variants determine an individual’s response to BRIUMVI or another antibody treatment. Nevertheless, the research supports further investigation into how genetic diversity and antibody biology may contribute to differences in treatment response across patient populations.
The pilot study is available in the Fc biology and genetic diversity presentation.
European BRILL Study Reports Real-World Treatment Experience
A separate presentation sponsored by Neuraxpharm reported interim 48-week findings from the non-interventional BRILL study, which evaluated real-world use of ublituximab in relapsing forms of MS.
The interim analysis included 169 patients. The proportion of patients experiencing a relapse decreased by 93% compared with the 12 months before starting BRIUMVI, while the on-treatment annualized relapse rate was 0.05.
Treatment satisfaction was also high. Among respondents, 94.6% indicated that they would choose BRIUMVI again.
The analysis found that infusion-related reactions declined over time, decreasing from 21.9% at the first infusion to 3.0% at Week 48.
These findings add to the growing body of observational evidence concerning ublituximab use in routine clinical practice. As an interim analysis from a non-interventional study, the results should be interpreted with consideration of the study design and the limitations of comparisons with the pretreatment period.
The data are available in the BRILL study presentation.
Late-Breaking Presentation to Highlight Initial Azer-Cel Findings in Progressive MS
In addition to the BRIUMVI presentations, TG Therapeutics announced that the abstract for a late-breaking oral presentation on azer-cel is available.
The presentation, titled First Clinical Evaluation of an Allogeneic CD19-Directed CAR T-Cell Therapy in Progressive Multiple Sclerosis: Initial Results from the Phase 1 TG-Azercel-101 Study, will discuss initial results from a Phase 1 study evaluating azer-cel in patients with PPMS.
Azer-cel is an allogeneic CD19-directed CAR T-cell therapy being investigated for its potential role in progressive MS. Unlike anti-CD20 antibody therapies, which target CD20-expressing B cells, CD19-directed CAR T-cell approaches use engineered immune cells to target cells expressing CD19.
The study represents an investigational approach to progressive MS, a form of the disease characterized by gradually worsening neurological function. Initial Phase 1 findings are expected to contribute early clinical information, but further studies will be needed to determine the therapy’s safety, activity, and potential role in treatment.
The oral presentation is scheduled for Friday, October 23, 2026, from 10:45 to 10:55 a.m. Eastern Time, during the Late-Breaking Abstracts scientific session. The presentation details are listed as Toronto-LBA-229 and Oral O135. Daniel Ontaneda, M.D., Ph.D., Professor of Neurology at the Cleveland Clinic Mellen Center, is the lead author.
Following the presentation, the data are expected to be made available through the company’s publications page.
TG Therapeutics Advances Its Multiple Sclerosis Development Strategy
Michael S. Weiss, Chairman and Chief Executive Officer of TG Therapeutics, said the breadth and consistency of the MSToronto2026 presentations reinforce the company’s confidence in BRIUMVI as a treatment option for relapsing MS.
Weiss highlighted the seven-year results, particularly the proportion of continuously treated patients who remained free from confirmed disability progression. He also emphasized the expanding real-world evidence concerning disease control, tolerability, and patient satisfaction, along with findings from patients transitioning from other anti-CD20 therapies.
He further noted that the Phase 3 ENHANCE results and Phase 1 subcutaneous findings could support additional administration options if the ongoing development and regulatory processes are successful.
All posters referenced in the announcement are available through the company’s publications page.
Overall, the MSToronto2026 presentations cover long-term clinical outcomes, real-world treatment experience, alternative administration strategies, immune biology, and emerging cellular therapy research. Together, the findings support TG Therapeutics’ continued evaluation of BRIUMVI and azer-cel across different aspects of multiple sclerosis care, while additional clinical and regulatory work will determine how these investigational developments may translate into future treatment options.
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 countries outside of the U.S. for the treatment of adult patients with RMS with active disease defined by clinical or imaging features.