TG Therapeutics has voluntarily withdrawn the pending Biologics License Application (BLA) and supplemental New Drug Application (sNDA) for the combination of ublituximab and Ukoniq® (umbralisib) for the treatment of adults with chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL).

Ukoniq is an oral inhibitor of phosphoinositide 3 kinase (PI3K) delta and casein kinase 1 (CK1) epsilon. In February 2021, the FDA granted accelerated approval to Ukoniq for the treatment of adults with relapsed or refractory marginal zone lymphoma (MZL) who have received at least 1 prior anti-CD20-based regimen; and for adults with relapsed or refractory follicular lymphoma (FL) who have received at least 3 prior lines of systemic therapy. The approval was based on overall response rate from the phase 2 UNITY-NHL trial (Clinicaltrials.gov: NCT02793583).

The decision to withdraw the pending applications was based on an initial review of data from the phase 3 UNITY-CLL trial (Clinicaltrials.gov: NCT02612311), which showed that the combination of Ukoniq and ublituximab, an investigational anti-CD20 monoclonal antibody, appeared to be associated with an increased risk of death in patients with CLL when compared with the control arm. The incidence of serious adverse events was also reported to be greater in the Ukoniq plus ublituximab treatment arm compared with the control arm.

In February 2022, the FDA issued a safety communication alerting health care professionals and patients regarding a possible increased risk of death with Ukoniq. Based on findings from the UNITY-CLL trial, the FDA suspended further enrollment of new patients in ongoing clinical trials of Ukoniq. 

The withdrawal of the BLA and sNDA for Ukoniq plus ublituximab in CLL has also prompted the Company to voluntarily withdraw Ukoniq from sale for its approved indications for MZL and FL.

Michael S. Weiss, Chairman and CEO of TG Therapeutics stated, “We were very disappointed to see that the recently updated overall survival data showed an increasing survival imbalance in favor of the control arm. Accordingly, we and our advisors determined that we should withdraw the BLA/sNDA for [Ukoniq and ublituximab] in CLL. Additionally, we made the difficult decision to withdraw Ukoniq from sale for the approved indications in MZL/FL.”

Reference

TG Therapeutics announces voluntary withdrawal of the BLA/sNDA for U2 to treat patients with CLL and SLL. News release. TG Therapeutics, Inc. Accessed April 15, 2022. https://www.globenewswire.com/news-release/2022/04/15/2423276/8790/en/TG-Therapeutics-Announces-Voluntary-Withdrawal-of-the-BLA-sNDA-for-U2-to-Treat-Patients-with-CLL-and-SLL.html