The FDA on Thursday warned about the possible increased risk of death or serious side effects with duvelisib (Copiktra) in adults with chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL).
Long-term results from the phase III DUO trial showed potentially worse overall survival (OS) with the PI3 kinase (PI3K) inhibitor versus ofatumumab (Arzerra), an anti-CD20 drug (HR 1.09, 95% CI 0.79-1.51), with a median OS 11 months shorter with duvelisib (52.3 vs 63.3 months).
OS also appeared potentially worse in patients who had at least two prior lines of therapy before starting duvelisib, the specific indication for the drug (HR 1.06, 95% CI 0.71-1.58).
Duvelisib was approved in 2018 for patients with relapsed or refractory CLL/SLL based on early results from the DUO trial. The randomized, open-label trial evaluated duvelisib versus the monoclonal antibody ofatumumab in 319 patients who had received at least one prior line of therapy. With limited OS data available at the time of the approval, the FDA required Secura Bio, the drug’s manufacturer, to submit a a final OS analysis at 5 years.
In its safety alert on Thursday, the FDA also pointed out that serious adverse events (AEs), grade ≥3 AEs, deaths due to AEs and treatment modifications due to AEs were all higher among patients receiving duvelisib. Serious AEs included infections, diarrhea, inflammation of the intestine and lungs, skin reactions, and elevated liver enzyme levels in the blood.
According to the FDA, these safety findings are similar to those of other medicines in the same PI3K inhibitor class, which were discussed at an FDA advisory committee meeting in April. Duvelisib had also received accelerated approval in follicular lymphoma, but Secura Bio voluntarily withdrew that indication last December.
The FDA said it is continuing to evaluate the safety of the drug and plans to hold a future public meeting to discuss the findings from the DUO trial, as well as whether duvelisib should continue to be prescribed for patients.
In the meantime, the FDA said healthcare professionals “should consider the risks and benefits of continuing Copiktra in the context of other available treatments,” and “advise patients receiving Copiktra of the possible increased risk of death and higher risk of serious adverse events.”
The FDA is also urging patients and healthcare professionals to report side effects involving duvelisib to the FDA MedWatch program.