Phase III trial of combination Zydelig (idelalisib) shows benefits in Chronic Lymphocytic Leukemia- Gilead Sciences

Gilead Sciences announced results from a prespecified interim analysis of a Phase III study (Study 115) evaluating Zydelig (idelalisib) in combination with bendamustine and rituximab (BR) for patients with previously treated Chronic Lymphocytic Leukemia. The analysis found a 67 percent reduction in the risk of disease progression or death (progression-free survival, PFS) in patients receiving Zydelig plus BR compared to BR alone. Additionally, all secondary endpoints, including overall survival (OS), achieved statistical significance in this interim analysis. Median PFS for patients receiving Zydelig plus BR was 23.1 months compared to 11.1 months for patients receiving placebo plus BR. Among patients with a 17p deletion or TP53 mutation (Zydelig plus BR: n=69; placebo plus BR: n=68), genetic abnormalities that have been linked to poor prognosis, there was a 50 percent reduction in the risk of disease progression or death.

The study also found a statistically significant benefit in OS, with a 45 percent reduction in the risk of death among patients receiving Zydelig plus BR compared to those receiving BR alone. Median OS has not been reached in either arm. The overall response rate (ORR) was 68 percent in the Zydelig arm and 45 percent for the control arm. Adverse events for the Zydelig plus BR and placebo plus BR arms, respectively, included neutropenia (60 versus 46 percent), febrile neutropenia (20 versus 6 percent) and diarrhea (7 versus 2 percent). Detailed results were presented during the late-breaking abstracts session at the Annual Meeting of the American Society of Hematology.

Comment: Sales of Zydelig could be hapmered by a FDA black-box warning that highlights such side effects as colitis, lung inflammation and potential fatal liver problems. Imbruvica from J&J doesn't have a black box warning.