After announcing that the FDA was investigating a possible death associated with its lymphoma drug Ukoniq (umbralisib), things are seemingly looking up for TG Therapeutics.
Last week, TG Therapeutics announced that the U.S. Food and Drug Administration was investigating a possible death associated with its lymphoma drug Ukoniq (umbralisib). The company is seemingly having a better week now, indicating they would present data from the ULTIMATE I and II Phase III trials of ublituximab in relapsing forms of multiple sclerosis (RMS) at the upcoming Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) annual forum. The forum will be held on February 24–26 in West Palm Beach, Fla.
The first poster is “Reduction in T1 Hypointense Lesions with Ublituximab vs Teriflunomide in the Phase III Ultimate I and II Studies in Relapsing Multiple Sclerosis.” The lead author is Bruce A. C. Cree, M.D., Ph.D., with UCSF Weill Institute for Neurosciences, University of California San Francisco.
The second poster is “Neutralizing Antibodies and Antidrug Antibodies in the Ublituximab Phase III ULTIMATE I and II Studies in Relapsing Multiple Sclerosis.” The lead author is Dr. Enrique Alvarez, M.D., Ph.D., University of Colorado, Aurora, Colorado.
The third poster is “Pharmacodynamics of B-Cell Depletion and Pharmacokinetics of the Novel Anti-CD20 Monoclonal Antibody Ublituximab in Patients with Relapsing Multiple Sclerosis.” The lead author is Dr. Edward J. Fox, M.D., Ph.D., Central Texas Neurology Consultants, Round Rock, Texas.
“We are pleased to have three abstracts accepted for presentation at the upcoming ACTRIMS forum, highlighting additional analyses from the ULTIMATE I & II Phase III trials,” said Michael S. Weiss, chairman and chief executive officer of TG Therapeutics. “Each new analysis continues to be encouraging and we believe reinforces the utility of ublituximab as a potential treatment option for patients with RMS. We look forward to sharing the full data sets at the upcoming ACTRIMS meeting.”
Ublituximab is an investigational glycoengineered monoclonal antibody. It is designed to target a unique epitope on CD20-expressing B-cells.
Last week, the FDA indicated it had “determined that initial findings from a clinical trial evaluating Ukoniq to treat a related type of cancer found a possible increased risk of death in patients taking the medicine.”
The drug is an oral PI3k delta and CK1 epsilon inhibitor. It is approved for adults with relapsed or refractory marginal zone lymphoma (MZL) who have received at least one prior anti-CD20-based treatment and for adults with relapsed or refractory follicular lymphoma (FL) who have received at least three prior lines of systemic therapy. They were approved under accelerated approval based on the overall response rate. Their continued approval depends upon verifying the clinical benefit in confirmatory clinical studies.
The FDA is informing patients and physicians that it is re-evaluating the drug’s risk-benefit profile for its approved uses. It plans to continue analyzing data from the Phase III UNITY clinical trial. It potentially will hold an advisory committee meeting to discuss the findings and determine the continued marketing of the drug. FDA also stated it “has also suspended enrollment of new patients in other ongoing clinical trials of Ukoniq while [the agency] continues to review the UNITY findings.”
Although UNITY was only being run with CLL patients, the agency is worried the safety signals may also apply to MZL and FL. They also indicated that other drugs in the same class had shown similar safety issues. As noted in Cancer Network in 2017, “Despite the therapeutic benefit, there have been concerns about the severe and sometimes fatal adverse effects of this class of drug. Several unusual side effects have poorly understood mechanisms; these include autoimmune dysfunction, opportunistic infections, skin toxicity, hypertension and hyperglycemia.”
