Ublituximab as Relapsing MS Therapy Under FDA Review
An FDA’s decision is expected on or before Sept. 28. The agency is not currently planning to hold an advisory committee meeting to discuss the application. Such meetings are held to seek the advice of an independent panel of experts when the FDA has questions or concerns about the submitted clinical data.
TG Therapeutics also plans to file a similar application to European Union’s regulatory agency.
“This is a major milestone for us as it is our first U.S. marketing application for an autoimmune indication,” Michael S. Weiss, chairman and CEO of TG Therapeutics, said in a press release. “We look forward to working with the FDA throughout this review process.”
Ublituximab is an antibody designed to reduce or prevent further neuronal damage in MS patients and slow disease progression by eliminating the immune B-cells that drive the immune attacks that characterize the disease. It does so by targeting CD20, a protein found on B-cells’ surface.
Administered into the bloodstream every six month, ublituximab was designed to have superior potency relative to current anti-CD20 antibody therapies, allowing for lower doses and shorter infusion times. In clinical trials, its infusion time was about one hour, the shortest to date.
If approved, ublituximab will be the third anti-CD20 antibody therapy available in the U.S. for relapsing MS, joining Roche’s Ocrevus (ocrelizumab), administered as a two-hour infusion every six months, and Novartis’ Kesimpta (ofatumumab), given at home through an under-the-skin injection once a month.
The regulatory submission of ublituximab was based on data from the ULTIMATE 1 (NCT03277261) and ULTIMATE 2 (NCT03277248) Phase 3 clinical trials, which tested ublituximab against Sanofi Genzyme’s Aubagio (teriflunomide) in a total of 1,094 relapsing MS patients from 10 countries.
Aubagio is an oral treatment approved for relapsing MS that is also thought to work by suppressing the activity of immune cells, namely B-cells and T-cells.
Nearly all participants (about 98%) had relapsing-remitting MS, while the remaining had secondary progressive MS with relapses. In both trials, patients were randomly assigned to either ublituximab or Aubagio (a 14 mg daily tablet) for 96 weeks (nearly two years).
Those in the ublituximab group received a four-hour infusion of 150 mg on day one and a one-hour infusion of 450 mg on day 15, before starting on treatment every six months.
Both studies met their main goal, with ublituximab-treated patients having significantly lower annualized relapse rates (less than 0.1 relapses per year) compared with those given Aubagio.
Ublituximab treatment was also associated with significantly fewer brain lesions, and significantly greater proportions of patients achieving no evidence of disease activity and confirmed disability improvement (less disability) relative to Aubagio.
Particularly, about a two times higher proportion of ublituximab-treated patients showed confirmed disability improvement for at least three months (12% vs. 6%) and sustained for over six months or more (9.6% vs. 5.1%).
The experimental therapy was also superior to Aubagio at slowing brain shrinkage in ULTIMATE 2 and at improving upper and lower motor function in both trials.
Ublituximab was generally well-tolerated with rates of adverse events comparable to Aubagio — about 88% in each group.
The ULTIMATE trials were conducted under the FDA’s special protocol assessment, which allows biopharmaceutical companies to meet with the agency to determine the best clinical trial design and size to support a potential marketing approval.