TG Reports 7-Year BRIUMVI Outcomes and Positive ENHANCE Results

TG Therapeutics reported updated clinical and real-world data for BRIUMVI (ublituximab-xiiy), its anti-CD20 monoclonal antibody for relapsing multiple sclerosis (RMS), at MSToronto2026, the 10th Joint ACTRIMS-ECTRIMS Meeting. The October 21, 2026, update included seven-year outcomes from ULTIMATE I and II, Phase 3 ENHANCE results, Phase 1 subcutaneous pharmacokinetic data and findings from real-world studies. The company also announced an upcoming presentation of initial Phase 1 results for azer-cel in progressive MS.

Seven-Year Data Show Sustained Disease Control

In the ULTIMATE I and II follow-up, patients receiving continuous BRIUMVI treatment had an annualized relapse rate (ARR) of 0.018 at Year 7. Overall, 88.3% remained free from disability progression confirmed over 24 weeks.

Confirmed disability progression occurred in 11.7% of continuously treated patients, compared with 17.4% of patients who initially received teriflunomide before switching to BRIUMVI (p=0.0148). Confirmed disability improvement was reported in 17.6% and 13.6%, respectively. The safety profile remained consistent, without an apparent increase in exposure-adjusted adverse-event rates over time.

These findings support sustained disease control with long-term treatment. However, the comparison between continuous-treatment and switch groups comes from the extension phase and does not establish that earlier BRIUMVI treatment caused better disability outcomes.

ENHANCE Supports a Single-Infusion Initiation Regimen

The Phase 3 ENHANCE trial met its primary endpoint, demonstrating bioequivalent drug exposure with a proposed single 600 mg intravenous infusion on Day 1 versus the approved initiation schedule of 150 mg on Day 1 and 450 mg on Day 15. Infusion-related reactions were comparable between regimens, with no Grade 3 or higher reactions reported.

The findings support further evaluation of a simplified initiation schedule, but bioequivalent exposure does not independently establish equivalent long-term clinical efficacy. The single-infusion regimen remains investigational.

Separately, Phase 1 testing of subcutaneous BRIUMVI showed mean bioavailability above 60% relative to intravenous administration. Pharmacokinetic modelling supports a quarterly subcutaneous regimen being evaluated in a fully enrolled Phase 3 trial. These data inform dose development but do not establish clinical efficacy of the subcutaneous formulation in RMS.

Real-World Studies Add Treatment Experience

In the Phase 4 observational ENABLE study, 99.2% of 1,076 participants remained relapse-free during BRIUMVI treatment, with an ARR of 0.014. First-dose infusion-related reactions occurred in 18.8%, and median infusion time was 63 minutes for the second, third and fourth infusions.

In the Neuraxpharm-sponsored BRILL study, an interim analysis of 169 patients found a 93% reduction in the proportion experiencing relapse compared with the 12 months before treatment. The on-treatment ARR was 0.05, and 94.6% of respondents said they would choose BRIUMVI again. Infusion-related reactions declined from 21.9% at the first infusion to 3.0% at Week 48.

Both studies provide useful real-world evidence, but their observational designs limit causal conclusions. BRILL’s before-and-after comparison is particularly susceptible to changes over time and regression to the mean.

Additional ENHANCE analyses found a 69% reduction in reported wearing-off symptoms by Week 24 among participants switching from ocrelizumab, sustained through Week 48. These patient-reported findings lack a control group. An exploratory immune-profile analysis involving 20 participants and a separate Fc-biology pilot remain hypothesis-generating.

Safety and Regulatory Context

BRIUMVI’s established risks remain relevant, including infusion reactions, infections, hepatitis B reactivation, progressive multifocal leukoencephalopathy, reduced immunoglobulins and liver injury. Patients require appropriate screening and monitoring according to the approved prescribing information.

The proposed single-infusion initiation schedule and quarterly subcutaneous formulation are not approved regimens. The current findings also do not establish BRIUMVI’s superiority over other anti-CD20 therapies.

Azer-cel in Progressive MS

TG Therapeutics has made available the abstract for the Phase 1 TG-Azercel-101 study of azer-cel, an allogeneic CD19-directed CAR T-cell therapy in primary progressive MS. The late-breaking oral presentation is scheduled for October 23, 2026. Detailed results should be assessed from the abstract and presentation before drawing conclusions about safety or activity.

Overall, the update strengthens the evidence for sustained disease control with BRIUMVI and supports continued investigation of more convenient dosing options. The long-term extension and observational findings require cautious interpretation, while both investigational dosing regimens still need further clinical and regulatory evaluation.

Reference

TG Therapeutics Highlights New Clinical Data Across Multiple Sclerosis Portfolio at MSToronto2026, TG Therapeutics, 21 October 2026

Study to Assess the Efficacy and Safety of Ublituximab in Participants with Relapsing Forms of Multiple Sclerosis (RMS) (ULTIMATE 1) (ULTIMATE 1), ClinicalTrials.gov ID NCT03277261

Study to Assess the Efficacy and Safety of Ublituximab in Participants with Relapsing Forms of Multiple Sclerosis (RMS) (ULTIMATE II), ClinicalTrials.gov ID NCT03277248

Study to Evaluate Safety, Efficacy and Pharmacokinetics (PK) of a Modified Regimen of Ublituximab (ENHANCE), ClinicalTrials.gov ID NCT05877963

A Study to Evaluate the Pharmacokinetics, Pharmacodynamics, Safety, Radiological and Clinical Effects of Subcutaneous Ublituximab in Participants with Relapsing Multiple Sclerosis (RMS), ClinicalTrials.gov ID NCT07211633

A Study to Assess the Safety and Clinical Activity of Azer-cel in Participants With B-cell Mediated Autoimmune Disorders, ClinicalTrials.gov ID NCT06680037