Announcement • Jun 04
TG Therapeutics, Inc. Announces Positive Results From Phase 1 Trial Evaluating Subcutaneous BRIUMVI
TG Therapeutics, Inc. announced positive pharmacokinetic (PK), pharmacodynamic (PD), safety, and tolerability data from its Phase 1 clinical trial evaluating a subcutaneous formulation of ublituximab (the active agent in BRIUMVI) in patients with relapsing forms of multiple sclerosis (RMS). Pharmacokinetic and pharmacodynamic data support quarterly subcutaneous BRIUMVI dosing regimen currently under evaluation in fully enrolled Phase 3 trial; Top-line Phase 3 data expected year-end 2026 or early 2027. Novel investigational high concentration subcutaneous formulation of BRIUMVI was well-tolerated with no new safety signals observed. Positive pharmacokinetic (PK), pharmacodynamic (PD), safety, and tolerability data from its Phase 1 clinical trial evaluating subcutaneous formulation of ublituximab (the active agent in BRIUMVI) as compared to IV BRIUMVI. The Phase 1 trial is evaluating the bioavailability, pharmacokinetics (PK), pharmacodynamics (PD), safety, and tolerability of a high-concentration (400 mg/2 mL) subcutaneous formulation of BRIUMVI compared to the currently approved intravenous (IV) formulation. To date, over 100 patients have been treated in the trial, including more than 80 patients who received subcutaneous BRIUMVI across multiple dose levels (50 mg 400 mg) in single and multiple dose cohorts. More than 225 subcutaneous injections of BRIUMVI were administered, of which over 75% were 400 mg (2 mL) injections. The overall concentration-time profile of subcutaneous BRIUMVI was consistent with expectations for a subcutaneous formulation, with a gradual absorption phase and lower peak concentrations relative to IV, and linear pharmacokinetics were observed over the entire dose range evaluated. Subcutaneous BRIUMVI demonstrated mean bioavailability of greater than 60% relative to IV administration, with the lower bound of the 95% confidence interval exceeding 55%. PK modeling and simulation informed by the Phase 1 bioavailability data support the conclusion that the quarterly subcutaneous dosing regimen that is being evaluated in the Phase 3 trial would achieve non-inferior total drug exposure over 24 weeks (AUC 0-Wk24) with an estimated geometric mean ratio (GMR) of 1.21 (with a lower bound of the 90% confidence interval at 1.15), as compared to IV BRIUMVI. The every other month subcutaneous dosing regimen that is also being evaluated in the Phase 3 trial, would achieve non-inferior total drug exposure over 24 weeks (AUC 0-Wk24) with an estimated GMR of 1.58 (with a lower bound of the 90% confidence interval at 1.50), as compared to IV BRIUMVI. The lower bound of the 90% confidence intervals for both dosing regimens being evaluated in Phase 3 would exceed the threshold required to establish non-inferiority (>0.80), which is the primary endpoint of the ongoing Phase 3 trial. Treatment with subcutaneous BRIUMVI resulted in B-cell depletion consistent with IV BRIUMVI, supporting the biological activity of the subcutaneous formulation. Subcutaneous administration was generally well tolerated, with treatment-emergent adverse events (TEAEs) consistent with the known safety profile of IV BRIUMVI. Local injection-site reactions were infrequent, occurring in less than 5% of patients, and systemic injection-related reactions occurred in approximately 21% of patients. Local and systemic injection reactions were not dose dependent and predominantly occurred at the first injection and resolved in 100% of patients. No serious injection-site reactions and no new safety signals were observed. The Phase 1 data, including the observed safety profile and modeled PK results, support the quarterly subcutaneous dosing regimen being evaluated in the Phase 3 trial. The Phase 3 dose of 400 mg in a 2mL injection is consistent with a volume that is suitable for at-home self-administration via an autoinjector device, which will be evaluated in a separate device bridging study to commence later this year. Final data through 24-weeks from this Phase 1 trial are expected to be presented at a future medical meeting. The Phase 3 trial is a randomized, open-label, parallel-group, multicenter trial designed to evaluate a quarterly and every other month dosing regimen of subcutaneous BRIUMVI compared to the approved IV regimen of BRIUMVI in adults with RMS. The primary endpoint of the Phase 3 trial is to demonstrate non-inferior drug exposure (levels in the blood) after administration of subcutaneous BRIUMVI compared to IV BRIUMVI over 24 weeks. Overall drug exposure for each arm is measured by area under the serum concentration-time curve from baseline through Week 24 (AUC 0-Wk24). AUC values within each treatment arm are summarized using geometric means and then compared between treatment arms using a ratio of those geometric means (GMR). Non-inferiority is achieved if the lower bound of the 90% confidence interval for the GMR of subcutaneous BRIUMVI relative to IV BRIUMVI is >0.80. Secondary endpoints include additional pharmacokinetic parameters, pharmacodynamics, safety, and radiological effects. Participants in the Phase 3 trial were randomized into one of three treatment arms: Arm A IV BRIUMVI (approved regimen): 150 mg on Day 1 and 450mg on Day 15, Week 24 and every 24 weeks thereafter. Total dose administered through Week 24: 600 mg. Arm B Subcutaneous BRIUMVI (every-other-month dosing): 400 mg administered on Day 1, Day 15, Week 8, and every 8 weeks thereafter. Total dose administered through Week 24: 1,600 mg. Arm C Subcutaneous BRIUMVI (quarterly dosing): 400 mg administered on Day 1 and 15, and Week 12, and every 12 weeks thereafter. Total dose administered through Week 24: 1,200 mg. The Phase 3 trial has completed enrollment, and topline results are expected in late 2026 or early 2027. 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 non-U.S. jurisdictions for the treatment of adult patients with RMS with active disease defined by clinical or imaging features.
