Ublituximab (TGTX-1101) is a glycoengineered anti-CD20 monoclonal antibody being developed by TG Therapeutics as a potential treatment for relapsing (RMS). Evidence shows that B-cells are activated during a relapse, and these immune system cells are found within acute lesions of the spinal cord, which suggests a role in MS flares.
Ublituximab targets a specific receptor on the CD20 antigen found on mature B-cells, depleting their number in the blood and central nervous system.
Originally developed to treat B-cell proliferative disorders like non-Hodgkin’s lymphoma and chronic lymphocytic leukemia, ublituximab is now also being studied in autoimmune diseases like MS, lupus and rheumatoid arthritis.
Ublituximab (TGTX-1101) research in RMS
TG Therapeutics released early data from a Phase 2 study (NCT0273877) assessing ublitiximab’s safety and efficacy in RMS patients in January 2017. The first part of the study, being led by Edward Fox, director of the Multiple Sclerosis Clinic of Central Texas and a professor at the University of Texas Medical Branch in Round Rock, evaluated ublitiximab at three different doses in three groups of patients (eight per group; infusions given on days 1 and 15 and week 24, and accelerated in two cohorts). In addition to safety and accelerated infusion tolerability, this initial part was to determine an optimal dosage by examining B-cell depletion up to week 24. (Data on other MS efficacy measures is still being collected and evaluated.)
Initial doses were administered to all as a 150 mg infusion on day 1. Then 450 mg on day 15, followed by either 450 mg or 600 mg at week 24, were given patients in group one, while accelerated infusions were in groups two and three on day 15 and week 24, including a one-hour infusion in the third group.
Data showed that ublituximab (TGTX-1101) was well-tolerated with no serious adverse events reported, with a median B-cell depletion of 99% in all patients, the company reported.
The Phase 2 trial is now moving into a planned second part, with a larger patient base and continued accelerated dosing. A Phase 3 study is also being planned for 2017. “B-cell depletion therapy has proven to be highly efficacious in the treatment of both relapsing and progressive forms of MS and we are highly encouraged by the rapid b-cell depletion that we have seen with TG-1101,” Fox said in the release, showing both a favorable safety profile and an ability “to be dosed in a rapid 1-hour infusion.”
Earlier ublituximab studies showed that the drug to be “potent” as a B-cell depleting agent.