Duvelisib Granted Priority Review for R/R CLL/SLL and FL

The US Food and Drug Administration (FDA) has announced acceptance of a filing with priority review for duvelisib, a first-in-class dual inhibitor of phosphoinositide 3-kinase (PI3K)-delta and PI3K-gamma, to treat patients with relapsed or refractory (R/R) chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL), and accelerated approval for treatment of relapsed or refractory follicular lymphoma (FL). The news was announced in a press release from Verastem, Inc.

Results published earlier this year from the phase III DUO trial showed that duvelisib improved median progression-free survival (PFS) by about 3.5 months in patients with CLL/SLL compared with the current standard of care, ofatumumab.

Commenting on the results of the study, lead researchers Ian Flinn, MD, PhD, of Sarah Cannon Research Institute in Nashville, Tenn., said, “These positive results from the randomized DUO study demonstrate that duvelisib prolongs progression-free survival with a manageable safety profile in patients with relapsed or refractory CLL/SLL, including in high-risk patients with the 17p deletion.”

For the DUO trial, 319 patients with CLL/SLL were randomly assigned to duvelisib at 25 mg twice daily or to ofatumumab. The median PFS of patients treated with duvelisib was 13.3 months compared with 9.9 months for ofatumumab. This translated into a 48% reduction in the risk for progression or death (hazard ratio [HR], 0.52; P < .0001).

The DUO study also specifically evaluated patients with 17p deletion. Among these patients, duvelisib also significantly prolonged PFS; median PFS was 12.7 months compared with 9 months with ofatumumab (HR,0.41; P < .0011).

Duvelisib was also tested as monotherapy in the single-arm, phase II DYNAMO trial. Duvelisib was administered at 25 mg twice daily to 129 patients with indolent non-Hodgkin lymphoma (INHL), including 83 patients with FL. According to findings presented at the 22^nd Congress of the European Hematology Association, the trial met its primary endpoint of improved overall response rate (ORR).

With 18 months follow-up, 36 of the 83 patients with double-refractory FL had responded to treatment, including 1 complete response and 35 partial responses, for an ORR of 43%. Eighty-three percent of patients with FL had a reduction in the size of their target lymph nodes, and the median duration of response was 7.9 months.

Verastem CEO Robert Forrester said that the priority review status granted by the FDA speaks to the need for treatments in patients with R/R CLL/SLL and FL.

“As an orally administered therapy, we believe duvelisib will provide an important treatment option for patients with CLL/SLL and FL, and for the physicians who treat them,” said Forrester. The FDA target action date is October 5, 2018.