Ublituximab Shows Reduced Relapse Risk and Fewer New Brain Lesions in Multiple Sclerosis

 As published in The New England Journal of Medicine (NEJM), in the phase 3 ULTIMATE trials (NCT03277261 and NCT03277248), ublituximab (UTX: TG Therapeutics, New York, NY) reduced risk of relapses and resulted in fewer active or new brain lesions in individuals with multiple sclerosis (MS).

The Food and Drug Administration (FDA) is reviewing marketing applications for ublituximab for the treatment of relapsing forms of multiple sclerosis (RMS) in adults.

Michael S. Weiss, chairman and chief executive officer of TG Therapeutics stated, “We are extremely pleased that the results from the ULTIMATE I & II trials have been published in The New England Journal of Medicine. We believe ublituximab’s novel mechanism of action, coupled with the convenience of a 1-hour infusion represents a potential advance for patients with RMS and we are pleased that this publication will share the ULTIMATE I and II data with a broad audience. We continue to be singularly focused on working toward the potential approval of ublituximab by the December 28, 2022 PDUFA goal date, and if successful, being prepared to launch early next year. We once again want to thank the patients that participated in ULTIMATE I and II and the healthcare providers at the sites that worked so hard on these trials.”

Lawrence Steinman, MD, Zimmermann professor of Neurology & Neurological Sciences, and Pediatrics at Stanford University and global study chair for the ULTIMATE I & II trials stated, “The ULTIMATE trials found ublituximab treatment, compared to teriflunomide, produced significantly lower annualized relapse rates, reduction in the total number of MRI-detectable lesions, as well as improved rates of patients achieving no evidence of disease activity (NEDA). If approved, the unique attributes of ublituximab, particularly its ability to be infused in a 1-hour infusion every 6 months following the first dose, may offer benefits to patients with relapsing forms of multiple sclerosis.”

In ULTIMATE I trial, the no evidence of disease activity (NEDA) was observed in 44.6% of those receiving ublituximab vs 15% of those receiving teriflunomide; in and ULTIMATE II trials, 43% and 11.4% achieved NEDA with ublituximab vs teriflunomide.

In the prespecified pooled analysis, at week 12, 5.2% of the participants who received ublituximab had worsening of disability confirmed compared with 5.9% of the participants who received teriflunomide (hazard ratio, 0.84; 95% CI, 0.50 to 1.41; P =.51).

At week 24, 3.3% of the ublituximab group had worsening of disability confirmed compared with 4.8% of the teriflunomide group (hazard ratio, 0.66; 95% CI, 0.36 to 1.21). At 12 weeks, 12% of participants treated with ublituximab had lessening of disability confirmed, as compared with 6% of the participants who received teriflunomide (hazard ratio, 2.16; 95% CI, 1.41 to 3.31). At 24 weeks, 9.6% of the participants who received ublituximab had lessening of disability confirmed compared with 5.1% of the participants who received teriflunomide (hazard ratio, 2.03; 95% CI, 1.27 to 3.25).

The ULTIMATE studies were multicenter double-blind double-dummy active-controlled phase 3 clinical trials. Participants were randomly assigned to teriflunomide treatment had daily oral doses plus placebo infusions for 96 weeks and were followed for an additional 20 weeks. Participants (n=1,094) had a diagnosis of relapsing MS using the McDonald 2010 criteria, expanded disability status scale (EDSS) scores of 0 to 5.5 and at least 2 documented relapses in the 2 years before enrollment or 1 relapse or 1 Gd+ lesion in the year before enrolling.

In both trials there was at least 1 adverse event, grade 3 or higher adverse events occurred in 21.3% of participants (n=116) who received ublituximab and in 14.1% (n=77) who received teriflunomide.

The most common adverse events seen with ublituximab were infusion-related reactions (47.7% with ublituximab vs 12.2% with placebo infusion).