82% of Patients Respond to BRIUMVI in Early Myasthenia Gravis Study

TG Therapeutics reported positive topline findings from a Phase 1 study of subcutaneous BRIUMVI (ublituximab‑xiiy) in acetylcholine receptor (AChR) antibody‑positive myasthenia gravis (MG). Eleven patients with substantial disease burden at baseline (mean MG‑ADL 8.24; mean QMG 12.0) received subcutaneous dosing at exposures comparable to the approved intravenous regimen.

By Week 24, 82% achieved the minimal clinically important difference (MCID) in MG‑ADL, defined as a ≥2‑point reduction, with a median time to response of 30 days. The mean MG‑ADL improvement was 4.6 points, underscoring clinically meaningful gains in daily functioning.

Safety outcomes were consistent with the established intravenous profile in multiple sclerosis, with no unexpected signals reported. Investigators noted the therapy was generally well tolerated, with adverse events limited to those typically associated with B‑cell depletion.

Expanding Development Beyond Multiple Sclerosis

BRIUMVI, a glycoengineered anti‑CD20 monoclonal antibody, is approved for relapsing forms of multiple sclerosis. Its mechanism of B‑cell depletion is increasingly recognized as a promising strategy in MG, where pathogenic autoantibodies drive neuromuscular dysfunction. The Phase 1 results support expansion of BRIUMVI’s development program into neuromuscular autoimmune disease.

Phase 2 Trial Design: Sequential Therapy Strategy

TG Therapeutics has initiated a potentially registration‑directed Phase 2 trial enrolling approximately 120 adults with MG. All participants will first receive a single induction cycle of efgartigimod, an FcRn inhibitor widely used in MG, consisting of four weekly infusions. Patients achieving ≥2‑point MG‑ADL improvement will then be randomized to BRIUMVI or placebo for 24 weeks.

The primary endpoint is time to clinical worsening, defined as a ≥2‑point increase in MG‑ADL or a myasthenic crisis requiring hospitalization. Secondary endpoints include QMG, MG‑Composite, and patient‑reported outcomes. Following the randomized phase, patients may enter a 72‑week open‑label extension to evaluate long‑term BRIUMVI therapy.

Strategic Differentiation and Regulatory Pathway

The sequential approach rapid antibody reduction with FcRn inhibition followed by durable immune modulation via B‑cell depletion positions TG’s program as differentiated from competitors focused solely on FcRn or complement inhibition.

CEO Michael Weiss emphasized the potential to reduce treatment burden while sustaining disease control, noting that the Phase 2 trial could serve as a pivotal study supporting future regulatory submission.

The trial will initially employ the approved intravenous regimen, with subcutaneous administration expected to be incorporated following completion of pharmacokinetic bridging studies in multiple sclerosis.

Reference

TG Therapeutics Announces Positive Topline Phase 1 Data for Subcutaneous BRIUMVI in Patients with Myasthenia Gravis and Initiation of Potential Registration Directed Randomized Phase 2 Trial | TG Therapeutics, Inc.