The Food and Drug Administration (FDA) has issued a safety alert warning that the results from a clinical trial evaluating the long-term safety of Copiktra (duvelisib) showed a possible increased risk of death and serious side effects.

Copiktra, an oral inhibitor of phosphoinositide 3-kinase (PI3K), received accelerated approval in 2018 for the treatment of adults with relapsed or refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) after at least 2 prior therapies. The indication was based on overall response rate from the single-arm, multicenter phase 2 DYNAMO study (ClinicalTrials.gov Identifier: NCT01882803).

As overall survival information was limited at the time of approval, the FDA had required Secura Bio to submit the final analysis at 5 years to evaluate the long-term safety of the drug. The DUO trial (ClinicalTrials.gov Identifier: NCT02004522) was a phase 3, randomized, open-label study that evaluated Copiktra vs the monoclonal antibody ofatumumab in 319 patients with relapsed or refractory CLL or SLL who received at least 1 prior line of therapy.

With a median follow-up of 63 months, results of the study revealed a possible increased risk of death with Copiktra when compared with ofatumumab (hazard ratio [HR], 1.09; 95% CI, 0.79-1.51). Among patients who received at least 2 prior lines of therapy (the FDA approved use), the HR was 1.06 (95% CI, 0.71-1.58). Median overall survival was 52.3 months (95% CI, 41.8-68) for the Copiktra group and 63.3 months (95% CI, 41.2-NE) for the ofatumumab group.

The safety analysis also showed a higher incidence of deaths due to adverse events, serious adverse events (including grade ≥3), and treatment modifications due to adverse events in the Copiktra arm. Side effects included infections, diarrhea, inflammation of the intestines and lungs, skin reactions, and high liver enzymes.

Based on these findings, the FDA recommends that health care providers evaluate the risks and benefits of continuing Copiktra vs prescribing an alternative therapy. Patients should be advised of the increased risk of death and serious adverse events associated with Copiktra use.

According to the FDA, the safety findings from the DUO study were similar to those observed with other drugs in the PI3K inhibitor class. Recently, the agency withdrew the approval of Ukoniq (umbralisib) for the treatment of marginal zone lymphoma and follicular lymphoma due to an increased risk of death observed in a clinical trial.

Reference

FDA warns about possible increased risk of death and serious side effects with cancer drug Copiktra (duvelisib). News release. June 30, 2022. https://www.fda.gov/drugs/drug-safety-and-availability/fda-warns-about-possible-increased-risk-death-and-serious-side-effects-cancer-drug-copiktra