FDA: major safety concerns with Ukoniq, PI3K inhibitor drug for treatment of lymphoma

March 2022 Pharma News Nalinee Pathak

Due to safety concerns, that include an elevated risk of death, the Food and Drug Administration (FDA) in the USA has issued a health alert about using the drug Ukoniq® (umbralisib) for lymphoma patients.

Umbralisib is an oral inhibitor of phosphoinositide 3 kinases (PI3K) delta and casein kinase I (CK1) epsilon. The FDA has granted accelerated approval for the use of Ukoniq for adults with relapsed or refractory marginal zone lymphoma (MZL) who had received at least one prior anti-CD-20-based regimen, and adults with relapsed or refractory follicular lymphoma (RRFL) who had received at least three prior lines of systemic therapy. The inhibitor received approval based on the overall response rate from the phase 2 UNITY-NHL trial.

An initial review of the phase 3 UNITY trial (clinicaltrials.gov: NCT02793583) saw that the combination of umbralisib plus ublituximab (an anti-CD20 monoclonal antibody) seems to be associated with an increased risk of death versus the control arm. Moreover, treatment-related adverse events were also higher in the combination treatment arm than the control arm.

Based on these findings from the UNITY trial, FDA has suspended enrollment of new patients in the ongoing clinical trial. The FDA oncologic drugs advisory committee (ODAC) may be convened to evaluate the safety evaluation of umbralisib. In safety communication, FDA noted that the Ukoniq for CLL is not approved, “however, we believe these findings have implications for its approved uses for MZL and FL.” Similar concerns were also observed with another PI3K inhibitor, Zydelig® (idelalisib).


FDA investigating the 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