PI3K inhibitor hit with an increased death risk warning from FDA after final trial results emerge
The FDA sent a fresh warning on Thursday about Secura Bio’s embattled PI3K inhibitor Copiktra (duvelisib), which may increase the risk of death and severe side effects for patients as a third-line treatment for adults with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL).
Copiktra won approval for both indications in 2018, but the FDA now says that after a median of 63 months follow-up in the Phase III that led to the approvals, the final overall survival results showed a possible increased risk of death for those taking Copiktra, with a hazard ratio of 1.09 (95% confidence interval [CI] 0.79, 1.51). In addition, 80/160 of those enrolled in the trial and on Copiktra ended up dying, compared with 70/159 of those on Novartis’ ofatumumab, FDA said.
“The rate of serious side effects, dose modifications, and deaths resulting from these side effects were also higher among patients who received Copiktra,” FDA added, telling doctors to discuss this new data with their patients and decide what the best action is moving forward.
This is just the latest warning for a class of drugs that has received increased scrutiny this year, with an FDA adcomm in April voting that all approvals for PI3K inhibitors should be supported by randomized data. PI3K inhibitors garnered more scrutiny recently in hematological malignancies after renewed toxicity concerns, inadequate dose optimization, trial design limitations of single-arm studies and concerning overall survival trends.
“These safety findings were similar for other medicines in the same PI3 kinase inhibitor class,” the FDA said in its warning on Copiktra.
Meanwhile, Secura Bio in April pulled an accelerated approval indication for Copiktra as a treatment for relapsed or refractory follicular lymphoma, after the firm failed to run the required confirmatory trial in this indication.
Secura Bio CFO Mark Spring told Endpoints News previously that Copiktra’s pulled accelerated approval was a money issue, adding:
We felt that completing the required Phase 3 trial would take too many years and would be too expensive. As you can understand, as a small company we invest our finite research funds in the areas that we feel will benefit patients the most and have a reasonable return on our investment. Secura Bio believes that our research funds are better spent on the development of COPIKTRA for the treatment of patients with relapsed and refractory Peripheral T-cell Lymphoma (r/r PTCL).
Copiktra, purchased by Secura Bio in September 2020 from Verastem in a deal valued at up to $311 million-plus royalties, works by blocking key signals that cause cancer cells to multiply, which may help reduce or stop the growth of certain types of cancer, according to the FDA.