Ublituximab (Briumvi), a monoclonal antibody targeting CD20, was approved for relapsing forms of multiple sclerosis (MS), including clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease, .
The FDA's decision was based on two identical phase III trials of people with relapsing MS, and .
At 96 weeks, ublituximab reduced annualized relapse rate (ARR) by 59% over teriflunomide (Aubagio) in ULTIMATE I and by 49% over teriflunomide in ULTIMATE II, reported Lawrence Steinman, MD, of Stanford University in Palo Alto, California, at the 2021 meeting of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS).
The mean number of gadolinium-enhancing lesions was 0.02 in the ublituximab group versus 0.49 in the teriflunomide group in ULTIMATE I and 0.01 versus 0.25, respectively, in ULTIMATE II. Trial results were subsequently published in .
"Over the past several years we have seen a dramatic shift in the MS treatment landscape towards the use of B-cell therapy, which has shown to be highly effective in reducing relapses in patients," Steinman said in a statement.
ULTIMATE I and II represent "an important milestone in the history of MS research as the first phase III study of an anti-CD20 monoclonal antibody in patients with relapsing MS to produce an annualized relapse rate of less than 0.10, which translates to less than one relapse in 10 years," he added.
Ublituximab is a glycoengineered drug that binds to B cells, triggering a series of immunologic reactions including antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity leading to cell destruction. The drug is designed to lack certain sugar molecules normally expressed on the antibody, which may enhance its ADCC activity.
In a pooled analysis of the ULTIMATE trials, the most common adverse events among ublituximab recipients were infusion-related reactions (47.7%), headache (34.3%), nasopharyngitis (18.3%), pyrexia (13.9%), and nausea (10.6%).
Serious infections occurred in 5.0% of the ublituximab group. Three deaths occurred among ublituximab recipients -- one each as a result of pneumonia, encephalitis after measles, and salpingitis after an ectopic pregnancy.
No cases of progressive multifocal leukoencephalopathy (PML) were seen over 96 weeks, though John Cunningham polyoma virus (JCV) antibodies resulting in PML have been observed in patients treated with other anti-CD20 antibodies and other MS therapies, TG Therapeutics said. MRI findings pointing to PML may be apparent before clinical symptoms, and monitoring for signs consistent with PML may be useful, the company added.
The drug is contraindicated for MS patients with active hepatitis B virus infection and those who have a history of life-threatening infusion reaction to ublituximab.
TG Therapeutics said it expects the drug to be available in the first quarter of 2023.