TG Therapeutics, Inc.  announced results from the ULTIMATE I & II Phase 3 trials evaluating ublituximab, the Company's investigational anti-CD20 monoclonal antibody, in patients with relapsing forms of multiple sclerosis (RMS), were published in The New England Journal of Medicine. Primary Endpoint: Annualized Relapse Rate (ARR) Results In ULTIMATE I, treatment with ublituximab resulted in an ARR of 0.08 (n=271), compared to 0.19 for teriflunomide (n=274), (p<0.001). In ULTIMATE II, treatment with ublituximab resulted in an ARR of 0.09 (n=272), compared to 0.18 for teriflunomide (n=272), (p=0.002).

MRI Results In the ULTIMATE I trial, the mean total number of gadolinium enhancing lesions per T1-weighted MRI scan was 0.02 in the ublituximab group and 0.49 in the teriflunomide group (rate ratio, 0.03; 95% CI, 0.02 to 0.06; P<0.001); in the ULTIMATE II trial, the corresponding numbers were 0.01 and 0.25 (rate ratio, 0.04; 95% CI, 0.02 to 0.06; P<0.001). In the ULTIMATE I trial, the mean total number of new or enlarging hyperintense lesions per T2-weighted MRI scan was 0.21 in the ublituximab group and 2.79 in the teriflunomide group (rate ratio, 0.08; 95% CI, 0.06 to 0.10; P<0.001); in the ULTIMATE II trial, the corresponding numbers were 0.28 and 2.83 (rate ratio, 0.10; 95% CI, 0.07 to 0.14; P<0.001). No Evidence of Disease Activity (NEDA) Results In ULTIMATE I, NEDA was observed in 44.6% of ublituximab treated patients and in 15% of the teriflunomide treated patients.

In ULTIMATE II, NEDA was observed in 43% of ublituximab treated patients and in 11.4% of teriflunomide treated patients. Prespecified Pooled Disability Results In the prespecified pooled analysis, 5.2% of the participants in the ublituximab group had worsening of disability confirmed at 12 weeks, as compared with 5.9% of the participants in the teriflunomide group (hazard ratio, 0.84; 95% CI, 0.50 to 1.41; P = 0.51); 3.3% of the participants in the ublituximab group had worsening of disability confirmed at 24 weeks, as compared with 4.8% of the participants in the teriflunomide group (hazard ratio, 0.66; 95% CI, 0.36 to 1.21). These results were not considered to be significantly different between treatment groups.

In the prespecified pooled tertiary analysis that was not included in the hierarchical analysis and from which no conclusions can be drawn, 12.0% of the participants who received ublituximab had lessening of disability confirmed at 12 weeks, as compared with 6.0% of the participants who received teriflunomide (hazard ratio, 2.16; 95% CI, 1.41 to 3.31); 9.6% of the participants who received ublituximab had lessening of disability confirmed at 24 weeks, as compared with 5.1% of the participants who received teriflunomide (hazard ratio, 2.03; 95% CI, 1.27 to 3.25). Safety/Tolerability In a pooled analysis of the two trials, 486 of 545 participants (89.2%) who received ublituximab and 501 of 548 participants (91.4%) who received teriflunomide had at least one adverse event. Grade 3 or higher adverse events occurred in 116 participants (21.3%) who received ublituximab and in 77 (14.1%) who received teriflunomide.

The most common adverse event associated with ublituximab was infusion related reactions (47.7% of patients who received ublituximab experienced at least one infusion-related reaction vs. 12.2% for the teriflunomide group). Based primarily on the results of the ULTIMATE I & II trials, marketing applications for ublituximab to treat patients with RMS have been accepted and are currently under review by the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA).

As previously announced, ublituximab was granted a Prescription Drug Fee User Act (PDUFA) goal date of December 28, 2022 by the FDA.