TG Therapeutics launches Phase 2 MG trial after positive BRIUMVI data
TG Therapeutics has reported positive topline Phase 1 results for subcutaneous BRIUMVI (ublituximab-xiiy) in patients with myasthenia gravis and simultaneously announced the start of a Phase 2 trial designed to serve as the basis for a potential regulatory submission — marking a substantive expansion of the anti-CD20 antibody beyond its approved indication in relapsing forms of multiple sclerosis.
In the Phase 1 cohort of 11 patients with acetylcholine receptor antibody-positive MG, 82% achieved the Minimal Clinically Important Difference in the MG Activities of Daily Living scale by Week 24, defined as a reduction of at least two points. The mean improvement was 4.6 points from a baseline mean MG-ADL of 8.24, and the median time to MCID was 30 days. The company said the safety profile appeared consistent with that of intravenous BRIUMVI in MS, with no new signals identified. Full data are expected to be presented at a future medical meeting.
The Phase 2 design
The newly initiated Phase 2 trial adopts a sequential induction-to-maintenance strategy. Approximately 120 patients will first receive a single induction cycle of efgartigimod — an FcRn inhibitor already approved for generalised MG — comprising four weekly infusions. Those who achieve a clinical response will then be randomised 1:1 to BRIUMVI or placebo for a 24-week controlled period, with the primary endpoint being time to clinical worsening, defined as a two-point or greater increase in MG-ADL or a myasthenic crisis requiring hospitalisation.
Patients completing the randomised period will be eligible for a 72-week open-label extension. The trial will initially use intravenous BRIUMVI, with the subcutaneous formulation to be incorporated once pharmacokinetic bridging studies — currently running in MS — are complete.
Chief executive Michael Weiss described the rationale as combining "the rapid clinical benefit associated with FcRn inhibition with the durable disease control provided by B-cell depletion," a positioning intended to reduce the treatment burden of ongoing FcRn therapy, which typically requires repeated infusion cycles to sustain effect.
Market and competitive context
Myasthenia gravis has attracted growing pharmaceutical attention over the past five years. Efgartigimod (argenx), ravulizumab (AstraZeneca/Alexion), and rozanolixizumab (UCB) have all received US approvals or supplemental indications in MG, competing primarily on speed of response. Anti-CD20 B-cell depletion in MG is less established: rituximab has been used off-label for years, and ocrelizumab (Roche) has been investigated in the indication, but no anti-CD20 antibody has yet secured a formal MG label. TG Therapeutics is positioning BRIUMVI's glycoengineered CD20 targeting — which the company says enables effective B-cell depletion at lower doses — as a potential differentiator.
The sequential efgartigimod-to-BRIUMVI design is a notable strategic choice: it co-opts an approved competitor's mechanism as an induction tool while positioning BRIUMVI as the durable maintenance backbone. Whether regulators will view a single Phase 2 study as sufficient for registration will depend on the trial's statistical rigour, sample size, and robustness of the primary endpoint — factors that remain to be demonstrated. The company has been explicit that the study is only "potentially" registration-directed, and investors should note the Phase 1 cohort of 11 patients is small for drawing firm efficacy conclusions.