Investigational targeted B-cell therapy demonstrates superior efficacy compared with teriflunomide, a commonly prescribed treatment for MS.
TG Therapeutics announced results from the ULTIMATE I (NCT03277261) and II (NCT03277248) phase 3 trials, evaluating ublituximab in individuals with relapsing forms of multiple sclerosis (RMS). The findings were 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,” Michael Weiss, chair and CEO of TG Therapeutics, said in a statement. “We continue to be singularly focused on working toward the potential approval of ublituximab by the December 28, 2022, [Prescriber Drug User Fee Act] goal date, and if successful, being prepared to launch early next year.”.
Ublituximab is an investigational targeted B-cell therapy, which shows superior efficacy compared with teriflunomide, a commonly prescribed treatment for multiple sclerosis.
If approved, ublituximab will be the first B-cell therapy for use in RMS that can be given as a 1-hour infusion every 6 months after the first dose.
The 2 trials demonstrated significant reductions in risk of relapses and a reduction in active or new brain lesions.
The primary endpoint in both trials was annualized relapsed rate (ARR) results.
In the ULTIMATE I trial, treatment with the drug resulted in an ARR of 0.08 compared with 0.19 for teriflunomide, while the ULTIMATE II trial resulted in an ARR of 0.09 compared with 0.18, respectively.
Additionally, the results of no evidence of disease activity in the ULTIMATE I trial was 44.6% for individuals treated with ublituximab and 15% for those treated with teriflunomide. In the ULTIMATE II trial, it was 43% and 11.4%, respectively.
In the ULTIMATE I trial, the mean total number of gadolinium-enhancing lesions per T1-weighted MRI scan was 0.02 for those in the ublituximab group and 0.49 in the teriflunomide group. The findings of the ULTIMATE II trial were 0.01 and 0.25, respectively.
The mean total number of new or enlarging hyperintense lesions per T2-weighted MRI scan for the ULTIMATE I trial was 0.21 in the ublituximab arm and 2.79 in the teriflunomide group. For the ULTIMATE II trial, the results were 0.28 and 2.83, respectively.
In the prespecified pooled disability analysis, approximately 5.2% of individuals in the ublituximab group had worsening of disabilities at 12 weeks compared with 5.9% in the teriflunomide arm. At week 24, the individuals with worsening of disability were 3.3% and 4.8%, respectively.
However, the results were not considered to be significantly different between the treatment groups.
Investigators did not include the prespecified pooled tertiary analysis, because no conclusions were drawn from the results.
Approximately 89.2% of individuals who received ublituximab and 91.4% who received teriflunomide had at least 1 adverse event (AE). Grade 3 or higher AEs occurred in approximately 21.3% and 14.1% of individuals, respectively.
The most common AE associated with ublituximab was infusion-related reactions, which occurred in approximately 47.7% of individuals, while 12.2% of individuals in the teriflunomide group experienced these reactions.
The European Medicines Agency and FDA are reviewing marketing applications for ublituximab for the treatment of RMS in adults.
TG Therapeutics announces results from the ULTIMATE I and II phase 3 trials of investigational ublituximab in RMS published in The New England Journal of Medicine. News release. TG Therapeutics. August 25, 2022. Accessed August 25, 2022. https://ir.tgtherapeutics.com/news-releases/news-release-details/tg-therapeutics-announces-results-ultimate-i-ii-phase-3-trials