FDA withdraws approval for TG Therapeutics P13K inhibitor

June 2, 2022

The U.S. FDA has withdrawn its approval of cancer drug Ukoniq, manufactured by TG Therapeutics, over safety concerns.

After updated findings from the UNITY-CLL trial continued to report a possible increased risk of death in patients receiving the treatment, the administration decided that the treatment risks outweighed the benefits. UNITY-CLL is a global, phase 3 randomized controlled clinical trial that examined the combination of ublituximab (TG's investigational anti-CD20 monoclonal antibody) plus Ukoniq in both patients who had never been treated before or those who suffered from relapsed or refractory chronic lymphocytic leukemia (CLL).

In Feb. 2021, Ukoniq made waves by becoming the first and only FDA-approved oral PI3K delta and CK1 inhibitor to treat marginal zone lymphoma (MZL) and follicular lymphoma (FL). PI3K-delta plays a crucial role in many cellular mechanisms, including proliferation, survival and differentiation and CK1 has also been implicated in the development of cancer.

Then, this past April, TG announced that because of the data from the UNITY-CLL trial, it would be voluntarily withdrawing the pending Biologics License Application (BLA)/supplemental New Drug Application (sNDA) for the combination of ublituximab and Ukoniq, for the treatment of adult patients with CLL and small lymphocytic lymphoma (SLL). The company also took the drug off the market.

PI3K inhibitors have been under additional scrutiny lately with concerns raised about whether or not they actually help cancer patients. A few months ago, the FDA voted to extend the review process for these drugs, citing that “While the trials show a favorable impact on efficacy endpoints … the overall survival results are concerning,” as said by Nicole Gormley, director of the division of hematologic malignancies II in the FDA’s Office of New Drugs.

Now, the FDA has asked providers not to prescribe Ukoniq to patients anymore and to find alternative routes of treatment. Other PI3K inhibitors on the market include Gilead’s Zydelig and Verastem’s Copiktra. Earlier in 2022, Gilead also pulled some of the accelerated approval indications for Zydelig.