The Food and Drug Administration (FDA) has withdrawn the approval of Ukoniq (umbralisib) for the treatment of marginal zone lymphoma (MZL) and follicular lymphoma (FL).

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 MZL who had received at least 1 prior anti-CD20-based regimen; and for adults with relapsed or refractory FL who had 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).

In February 2022, an initial review of data from the phase 3 UNITY-CLL trial (Clinicaltrials.gov: NCT02793583) in patients with chronic lymphocytic leukemia (CLL) showed that the combination of Ukoniq and ublituximab, an investigational anti-CD20 monoclonal antibody, appeared to be associated with an increased risk of death when compared with the control arm. 

Based on these findings, TG Therapeutics voluntarily withdrew Ukoniq from the market for its approved uses, as well as the pending applications for CLL and small lymphocytic lymphoma.

According to the FDA, updated findings from the UNITY-CLL trial continue to show a possible increased risk of death among patients who received Ukoniq. As a result, the Agency has determined that the risks associated with the drug outweigh its benefits.

The FDA is recommending health care providers discontinue prescribing Ukoniq and switch patients to alternative therapies. TG Therapeutics will provide Ukoniq, in limited circumstances, under expanded access to patients who may be receiving benefit from treatment.

Adverse events related to Ukoniq and other medications should be reported to the FDA’s MedWatch program.

Reference

FDA approval of lymphoma medicine Ukoniq (umbralisib) is withdrawn due to safety concerns. News release. US Food and Drug Administration. Accessed June 1, 2022. https://www.fda.gov/drugs/drug-safety-and-availability/fda-approval-lymphoma-medicine-ukoniq-umbralisib-withdrawn-due-safety-concerns