FDA Accepts Ublituximab Biologics License Application for Relapsing MS


The FDA has set a prescription drug user fee act goal date of September 28, 2022, for the investigational treatment from TG Therapeutics.

Michael S. Weiss, chairman and CEO, TG Therapeutics

Michael S. Weiss

A biologics license application (BLA) for ublituximab, an investigational glycoengineering anti-CD20 monoclonal antibody, was accepted by the FDA for treatment of relapsing forms of multiple sclerosis (RMS), TG Therapeutics has announced. Currently, the FDA does not plan to hold an advisory committee meeting to discuss the application and has set a prescription drug user fee goal date of September 28, 2022.1

Following positive results from the ULTIMATE 1 and 2 trials (NCT03277261; NCT03277248)), identical phase 3 studies that evaluated ublituximab compared to teriflunomide (Aubagio; Sanofi) in patients with RMS, the BLA was submitted in September 2021. Both trials were conducted under a special protocol assessment established with the FDA. 

“We are excited to share that we have received formal communication from the FDA, and the BLA for ublituximab to treat relapsing forms of MS has been accepted and granted a standard review,” Michael S. Weiss, chairman and CEO, TG Therapeutics, said in a statement.1 “This is a major milestone for us as it is our first US marketing application for an autoimmune indication. We look forward to working with the FDA throughout this review process.”

About ULTIMATE 1 and 2

Results from ULTIMATE 1 and 2 were announced earlier this year at the 7th Congress of the European Academy of Neurology, June 19-22, 2021, with investigators concluding that ublituximab met its primary end point in significantly reducing annualized relapse rate (ARR) and MRI parameters over a 96-week period, when compared to teriflunomide (P <.005 in each trial).2-4

A total of 1094 patients from 10 countries were enrolled in the studies, and participants were randomized 1:1 to receive either teriflunomide or ublituximab, then assessed on ARR at 96 weeks. In both studies, a 450-mg dose of ublituximab was administered via 1-hour intravenous infusion every 6 months. This followed an infusion on day 1 of the trial of 150 mg over the course of 4 hours and another infusion on day 15 of 450 mg over 1 hour. Teriflunomide was administered via 14-mg oral tablets that were taken once a day.

In ULTIMATE 1 (n = 673), treatment with ublituximab resulted in an ARR of 0.076, compared with 0.188 for those treated with teriflunomide, representing a relative reduction of 60% (ARR ratio, 0.406 [95% CI, 0.268-0.615]; P <.0001). In ULTIMATE 2 (n = 660), ARRs at 96 weeks were 0.091 and 0.178 in the ublituximab and teriflunomide groups, respectively, equating to a 49% relative reduction (ARR ratio, 0.509 [95% CI, 0.330-0.784]; P = .0022).

The total number of T1 gadolinium-enhancing lesions were reduced when using ublituximab treatment by 97% and 96% relative to treatment with teriflunomide in ULTIMATE 1 and 2, respectively (P <.0001). Additionally, relative reductions of 92% and 90% for new or enlarging T2 lesions were observed by treatment with ublituximab in ULTIMATE 1 and 2, respectively (P <.0001). 

Both trials reported similar numbers of adverse events, with the most common being infusion-related reaction, headache, nasopharyngitis, and lymphopenia. There were 3 deaths that occurred during the trial, which were all in the ublituximab group and the result of encephalitis, salpingitis, and pneumonia. Investigators noted the pneumonia case was potentially related to treatment and saw no cases of progressive multifocal leukoencephalopathy.

Additional Clinical Context

Lead investigator for both trials, Lawrence Steinman, MD, Zimmermann Professor of Neurology and Neurological Sciences, and Pediatrics at Stanford University, sat down with NeurologyLive® to discuss findings following the submission of the BLA. Learn more about what he had to say about expanded data from both trials in the video below. 

1. TG Therapeutics announces FDA acceptance of biologics license application for ublituximab as a treatment for patients with relapsing forms of multiple sclerosis. News release. TG Therapeutics. December 14, 2021. Accessed December 14, 2021. https://www.biospace.com/article/releases/tg-therapeutics-announces-fda-acceptance-of-biologics-license-application-for-ublituximab-as-a-treatment-for-patients-with-relapsing-forms-of-multiple-sclerosis/ 
2. TG Therapeutics submits biologics license application to the US Food and Drug Administration for ublituximab as a treatment for patients with relapsing forms of multiple sclerosis. News release. TG Therapeutics, Inc. September 30, 2021. Accessed December 14, 2021. https://www.globenewswire.com/news-release/2021/09/30/2306091/8790/en/TG-Therapeutics-Submits-Biologics-License-Application-to-the-U-S-Food-and-Drug-Administration-for-Ublituximab-as-a-Treatment-for-Patients-with-Relapsing-Forms-of-Multiple-Sclerosis.html
2. TG Therapeutics announces presentation of data from the ULTIMATE 1 & 2 phase 3 trials of ublituximab in multiple sclerosis at 7th Congress of the European Academy of Neurology. News release. TG Therapeutics. June 18, 2021. Accessed December 14, 2021. https://www.biospace.com/article/releases/tg-therapeutics-announces-presentation-of-data-from-the-ultimate-i-and-ii-phase-3-trials-of-ublituximab-in-multiple-sclerosis-at-7th-congress-of-the-european-academy-of-neurology/
3. Steinman L, Fox E, Hartung HP, et al. Ublituximab versus teriflunomide in relapsing multiple sclerosis: results of the phase 3 ULTIMATE 1 and 2 trials. Presented at the 7th Congress of the European Academy of Neurology; June 19-22. Abstract A-21-00763
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