TG Therapeutics Releases Briumvi Clinical Trial Data

TG Therapeutics announced pharmacokinetic, pharmacodynamic, safety, and tolerability data from its Phase 1 clinical trial evaluating subcutaneous formulation of ublituximab as compared to IV Briumvi. 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 with an estimated geometric mean ratio of 1.21, 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 with an estimated GMR of 1.58, 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, 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 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.