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NEW YORK—Multiple sclerosis (MS) is the most common cause of non-traumatic disability in young adults. Nearly one million people are living with MS in the United States, with about 300,000 people receiving treatment. Roughly 85 percent are initially diagnosed with the relapsing remitting form of MS (RRMS), which is the most common form of MS and is characterized by episodes of new or worsening signs or symptoms, followed by periods of recovery.
“With a current market of $18 to $20 billion and a projected market of $25 billion, MS is a large and growing problem,” said Michael Weiss, CEO and president of TG Therapeutics, which was founded in 2012 to create the best possible treatment options for patients with B cell diseases, focusing on autoimmune and oncology applications. The company began by licensing a potential drug from LFB Biotech, a subsidiary of Ministry of Health, France.
Positive Phase 2 data from the evaluation of TG Therapeutics’ anti-CD20 drug candidate ublituximab (TG-1101) in MS was published in the Multiple Sclerosis Journal in April. The objective of the study was to determine the optimal dose, infusion time and activity of ublituximab in relapsing multiple sclerosis. The data demonstrate that ublituximab was generally well tolerated across all cohorts, including those patients receiving one-hour infusions for the 450 mg dose currently being studied in the Phase 3 ULTIMATE MS program, and the study met its pre-specified endpoints. Safety data was available from all 48 patients and demonstrated that ublituximab was generally well tolerated, with no patients discontinuing due to a drug-related adverse event (AE). The company expects to report top-line data for its fully enrolled Phase 3 program in the second half of 2020.
The principal investigator for the Phase 2 study was Dr. Edward Fox, director of the Multiple Sclerosis Clinic of Central Texas at Central Texas Neurology Consultants and clinical associate professor at the University of Texas Dell Medical School. According to Fox, “The encouraging clinical data we have published illustrate the potential for ublituximab in the treatment of patients with relapsing forms of multiple sclerosis. The compelling efficacy findings and favorable tolerability profile reported in this Phase 2 study, along with the one-hour infusion time, are promising and support a differentiated profile for ublituximab.”
Ublituximab, a novel glycoengineered monoclonal antibody, targets a specific and unique epitope on the CD20 antigen, which is found on mature B lymphocytes. The drug candidate offers enhanced B-cell targeting through antibody-dependent cellular cytotoxicity (ADCC). Greater ADCC may allow lower doses and shorter infusion times versus other anti-CD20 monoclonal antibodies.
Ublituximab’s mechanism of action is similar to the approved anti-CD20 monoclonal antibodies, but it has been bioengineered to remove certain naturally occurring sugar molecules from the anti-CD20 antibody in a process called glycoengineering. Removing the sugar molecules enhances the compound's potency, with data showing 50 to 100 times greater activity than non-bioengineered anti-CD20 antibodies. Ublitixumab is administered via a 1-hour infusion every six months, as compared to 3.5- to 4-hour infusions every six months for an approved anti-CD20.
“Ublitixumab is engineered to be extremely potent,” Weiss noted. “It binds to circulating B cells. When it attaches, it calls in the immune system to kill cells. The body does this naturally when it’s working. The external antibodies make the immune system kick into action to kill cells.”
Weiss expects to have the Phase 3 data on ublituximab by the third or fourth quarter of 2020. If the results are positive, he expects the company to file with the FDA for Fast Track status, and ublituximab could be on the market by late 2021.
TG Therapeutics has several other prospective drugs in the pipeline. The company completed its first NDA submission, a rolling submission to the FDA requesting accelerated approval for umbralisib as a treatment for patients with previously treated marginal zone lymphoma (MZL) and follicular lymphoma (FL). The FDA previously granted umbralisib Breakthrough Therapy Designation for MZL and orphan drug designation for MZL and FL. TG Therapeutics also presented preclinical data for TG-1701, its highly selective Bruton’s kinase (BTK) inhibitor, at the 2020 American Association for Cancer Research annual meeting. TG-1701 was shown to be just as active and more selective for BTK than ibrutinib, and additional anti-tumor inhibition was seen when TG-1701 was combined with umbralisib plus ublituximab.