The U.S. Food and Drug Administration (FDA) is investigating a possible increased risk of death associated with umbralisib (Ukoniq), a kinase inhibitor including PI3K-delta and CK1-epsilon, approved to treat marginal zone and follicular lymphomas.
The FDA determined that initial findings from the phase III UNITY clinical trial, which is evaluating umbralisib to treat chronic lymphocytic leukemia, found a possible increased risk of death in patients treated with the agent. Because of the seriousness of this safety concern and the similarities between the two types of cancer for which this drug is approved and the type of cancer that was studied in the clinical trial, the FDA is alerting patients and health-care professionals that they are reevaluating this risk against the benefits of umbralisib for its approved uses.
The FDA is continuing to evaluate the results from the UNITY trial and may also hold a future public meeting to discuss these findings and explore the continued marketing of umbralisib. Enrollment of new patients in other ongoing clinical trials of umbralisib has also been suspended while the FDA continues to review the UNITY findings. The agency will communicate its final conclusions and recommendations when it has completed its review or has more information to share.
More About Umbralisib and UNITY
Umbralisib was approved in February 2021 to treat adults with relapsed or refractory marginal zone lymphoma who have received at least one prior anti-CD20–based regimen, and adult patients with relapsed or refractory follicular lymphoma who have received at least three prior lines of systemic therapy.
The FDA conducted an initial review of data from UNITY, a phase III, randomized, controlled clinical trial in patients with chronic lymphocytic leukemia. The trial is evaluating umbralisib in combination with the novel monoclonal antibody ublituximab, which targets the CD20 protein, compared to the control arm, in which patients received standard treatment.
The results showed a possible increased risk of death in patients receiving the combination of umbralisib and the monoclonal antibody compared to the control arm. Those receiving the combination of umbralisib and the monoclonal antibody also experienced more serious adverse events than those in the control arm. The UNITY trial was conducted in patients with CLL, which is not an approved use, but rather, a use of this drug that is being studied; however, the FDA believes these findings have implications for its approved uses for marginal zone and follicular lymphomas. In addition, clinical trials of other medicines in the same PI3 kinase inhibitor class as umbralisib have shown similar safety concerns.
Health-care professionals should review patients’ progress on umbralisib and discuss with them the risks and benefits of continuing umbralisib in the context of other available treatments. Patients should talk to their health-care professionals about the risks and benefits of umbralisib or any concerns they may have, including about possible alternative treatments.
We urge health-care professionals and patients to report side effects involving umbralisib or other medicines to the FDA MedWatch program.
