Ublituximab, Potential Relapsing MS Therapy, Up for FDA Approval

TG Therapeutics  has applied to the U.S. Food and Drug Administration (FDA) for approval of ublituximab, the company’s investigational anti-CD20 monoclonal antibody therapy for relapsing forms of multiple sclerosis (RMS).

Its application was based on data from the ULTIMATE 1 (NCT03277261) and ULTIMATE 2 (NCT03277248) Phase 3 studies that demonstrated ublituximab was superior to the approved therapy Aubagio (teriflunomide) in lowering the frequency of MS relapses over two years.

“The submission of this BLA [biologics license application] for ublituximab to treat patients with [relapsing] MS marks a major milestone for us, being our first submission of a marketing application for an autoimmune indication,” Michael S. Weiss, CEO of TG Therapeutics, said in a press release.

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“Multiple sclerosis is a chronic and potentially disabling disease that affects nearly 1 million Americans. We believe ublituximab has the potential to offer an important new treatment option for these patients, and we look forward to working closely with the FDA on this submission,” Weiss added.

Ublituximab is an antibody designed to target CD20, a protein found on the surface of B-cells, immune cells known to drive the altered inflammatory response that damages nerve fibers in MS. When ublituximab binds to CD20, it triggers the death of B-cells, thereby reducing their numbers and suppressing the immune attack on nerve fibers.

Additionally, ublituximab is uniquely designed to lack certain sugar molecules that are normally attached to antibodies. Removing these sugars — a process known as glycoengineering — increases the therapy’s potency.

Potentially, with higher potency, ublituximab can be administered at lower doses to achieve the same effect compared to other medications.

The ULTIMATE studies evaluated ublituximab’s safety and efficacy against Sanofi Genzyme’s Aubagio in a total of 1,094 adults across 10 countries. Most participants (about 98%) were diagnosed with relapsing-remitting MS (RRMS), while the remaining had secondary progressive MS (SPMS) with relapses.

Participants were randomly assigned to treatment with either ublituximab or Aubagio. Those on ublituximab received a four-hour, 150 mg infusion on day one and a one-hour infusion of 450 mg on day 15, followed by one-hour, 450 mg infusions every six months for 96 weeks (almost two years). A 14 mg tablet of Aubagio was given daily.

Both trials met their primary goal, demonstrating that ublituximab treatment was superior to Aubagio at lowering annualized relapse rates (ARR) or the number of relapses per year. In ULTIMATE I, ublituximab-treated patients had an ARR of 0.076 and 0.091 in ULTIMATE II — representing rates 50% to 60% lower than with Aubagio over two years.

More patients were also seen to have a confirmed disability improvement lasting at least 12 weeks in the ublituximab group than those on Aubagio — 12% vs. 6%, and to have improvements sustained over 24 weeks or more — 9.6% vs. 5.1%. Regardless of medication given, a low number of patients experienced disability progression.

If approved, ublituximab will be the third anti-CD20 antibody therapy available to relapsing MS patients in the U.S., joining Roche’s Ocrevus (ocrelizumab), administered as a two-hour infusion every six months, and Novartis’ Kesimpta (ofatumumab), a monthly under-the-skin injectable done at home.

Of note, the ULTIMATE studies operated under a special protocol assessment agreement with the FDA, which allowed TG to meet with the agency to guide trial design in support of potential approval.

“We want to thank the patients and their families, as well as the physicians and their research teams, who participated in our ULTIMATE I and II trials,” Weiss said.