NEJM Publishes Data Touting Efficacy of TG Therapeutics’ MS Drug

While TG Therapeutics awaits a decision from global regulators on possible approval of its relapsing/remitting multiple sclerosis (RMS) drug candidate ublituximab, the company published results from two Phase III trials in The New England Journal of Medicine.

Ublituximab is an investigational glycoengineered monoclonal antibody that targets a unique epitope on CD20-expressing B-cells. In the clinical trials, it demonstrated significant reductions in risk of relapses, as well as reduction of active or new brain lesions. If approved, ublituximab will be the first B-cell therapy for use in RMS patients that can be given as a 1-hour infusion every 6 months, following the first dose, the company noted.

The FDA set a PDUFA date of Dec. 28, 2022, for ublituximab - three months later than initially expected. In May, the deadline was extended after the regulatory agency requested additional data.

Relapsing/ remitting multiple sclerosis is the most common form of the disease and is characterized by episodes of new or worsening signs or symptoms followed by periods of recovery. It is estimated that nearly 1 million people are living with MS in the United States and approximately 85% are initially diagnosed with RRMS, TG noted.

Ublituximab is designed to bind to the B-cell and trigger a series of immunological reactions, including antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity. This leads to cellular destruction. Additionally, the drug is designed to lack certain sugar molecules normally expressed on the antibody, which TG noted has been shown to enhance its potency.

Michael S. Weiss, chairman and CEO of TG, said the company is pleased the results from the ULTIMATE I & II trials have been published in the NEJM.

“We believe ublituximab’s novel mechanism of action, coupled with the convenience of a one-hour infusion represents a potential advance for patients with RMS and we are pleased that this publication will share the ULTIMATE I and II data with a broad audience,” Weiss said in a statement.

Bot ULTIMATE I and II met their primary endpoints. Data showed that ublituximab demonstrated a statistically significant reduction in annualized relapse rate (ARR) compared to teriflunomide (Sanofi’s Aubagio) over a 96-week period. Study data also showed a significant improvement in the No Evidence of Disease Activity (NEDA) markers.

In the ULTIMATE I study, NEDA was observed in 44.6% of ublituximab treated patients and in 15% of the teriflunomide treated patients. In ULTIMATE II, NEDA was observed in 43% of ublituximab-treated patients and in 11.4% of teriflunomide-treated patients, the company reported.

Infusion-related reactions were the most common adverse event associated with ublituximab. Trial data showed that 89.2% of patients, 486 of 545, who received ublituximab and 91.4%, 501 of 548, who received teriflunomide had at least one adverse event.

Lawrence Steinman, a professor of neurology and neurological sciences at Stanford University and global study chair for the ULTIMATE I & II trials, said the clinical programs found that treatment with ublituximab not only lowered ARR compared to Aubagio, but improved NEDA rates and reduced the total number of MRI-detectable lesions in patients. Steinman noted that ublituximab’s infusion rate may offer improved quality of life for patients with relapsing forms of multiple sclerosis.

“We continue to be singularly focused on working toward the potential approval of ublituximab by the Dec. 28, 2022 PDUFA goal date, and if successful, being prepared to launch early next year,” Weiss said.

In addition to regulatory review in the U.S., TG has also filed for potential approval in Europe.