TG Therapeutics (Nasdaq: TGTX) reported Phase I data showing that subcutaneous ublituximab (Briumvi), its glycoengineered anti-CD20 B-cell depleting antibody, produced clinically meaningful improvements in myasthenia gravis (MG) patients. The firm indicated that a Phase II trial will be initiated testing a sequential treatment strategy pairing an FcRn inhibitor for rapid symptom control followed by ublituximab for sustained B-cell depletion.
TG is intent on expanding Briumvi beyond its approved multiple sclerosis indication into a generalized MG market that has grown substantially more competitive. The Phase II design — using argenx's Vyvgart (efgartigimod alfa) as an induction agent before randomizing to ublituximab or placebo — is an unusual attempt to combine two mechanistically distinct drug classes in a sequential regimen.
Trial data
The Phase I cohort enrolled 11 adults with acetylcholine receptor antibody-positive MG (mean age 74; mean baseline MG-ADL 8.24), receiving subcutaneous ublituximab at exposures demonstrated to be at least equivalent to the approved intravenous regimen. At Week 24, 82% of patients achieved the minimal clinically important difference in MG-ADL (defined as a ≥2-point decrease), with a median time to MCID of 30 days. Mean MG-ADL improvement was 4.6 points. The safety profile was described as generally consistent with the established intravenous Briumvi profile in MS. These are small-sample, uncontrolled data and should be interpreted with caution; the absence of a comparator arm precludes conclusions about relative efficacy.
The Phase II trial, now enrolling approximately 120 patients, uses a single induction cycle of efgartigimod (four weekly infusions), then randomizes MG-ADL responders 1:1 to intravenous ublituximab or placebo for 24 weeks. The primary endpoint is time to clinical worsening, defined as a ≥2-point MG-ADL increase or myasthenic crisis requiring hospitalization. A 72-week open-label extension follows.