The Food and Drug Administration (FDA) is alerting health care professionals and patients about a possible increased risk of death with the lymphoma medication Ukoniq (umbralisib).
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).
An initial review of data from the phase 3 UNITY 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. The incidence of serious adverse events was also reported to be greater in the Ukoniq plus ublituximab treatment arm compared with the control arm.
Based on these findings, the FDA has suspended enrollment of new patients in ongoing clinical trials of Ukoniq pending further review of data from the UNITY trial.
In a safety communication, the FDA noted that the use of the Ukoniq in CLL patients is not an approved use; “however, we believe these findings have implications for its approved uses for MZL and FL.” Similar safety concerns were reported in clinical trials investigating another PI3K inhibitor, Zydelig (idelalisib).
The Agency is recommending that health care providers review their patients’ progress on Ukoniq and discuss the risks and benefits associated with continued use.
Adverse events related to Ukoniq and other medications should be reported to the FDA’s MedWatch program.
- FDA investigating possible increased risk of death with lymphoma medicine Ukoniq (umbralisib). News release. US Food and Drug Administration. Accessed February 3, 2022. https://www.fda.gov/drugs/development-approval-process-drugs/fda-investigating-possible-increased-risk-death-lymphoma-medicine-ukoniq-umbralisib
- FDA alerts healthcare professionals about clinical trials with Zydelig (idelalisib) in combination with other cancer medicines. News release. US Food and Drug Administration. March 14, 2016. Accessed February 3, 2022. https://www.fda.gov/drugs/drug-safety-and-availability/fda-alerts-healthcare-professionals-about-clinical-trials-zydelig-idelalisib-combination-other