Phase 3 Results for Zydelig With Bendamustine and Rituximab

Gilead Sciences, Inc. announced results from a prespecified interim analysis of a Phase 3 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 (hazard ratio (HR) = 0.33; 95 percent CI: 0.24, 0.45; p<0.0001). Additionally, all secondary endpoints, including overall survival (OS), achieved statistical significance in this interim analysis. 

Zydelig is approved in the United States in combination with rituximab for patients with relapsed CLL for whom rituximab alone would be considered appropriate therapy due to comorbidities. Based on the Study 115 results, Gilead plans to submit supplemental regulatory filings in the U.S. and Europe early next year. Study 115 enrolled 416 adult patients with previously treated CLL whose disease had progressed less than 36 months following completion of prior therapy, and was not refractory to bendamustine. Eligible patients were randomized (1:1) to receive six cycles of BR over 24 weeks with either Zydelig 150 mg or placebo taken orally twice daily until disease progression or unacceptable toxicity. In November, the trial was unblinded following the recommendation of an independent Data Monitoring Committee.

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 (HR=0.55; 95 percent CI: 0.36, 0.86; p=0.008). 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.

AbbVie released PHASE 1 Clinical Data of VENETOCLAX

AbbVie announced the online publication of new data in the New England Journal of Medicine (NEJM) showing some patients with relapsed/refractory chronic lymphocytic leukemia (CLL) treated with venetoclax experienced a response, including complete responses. The article reports data from Arm A of the study, in which all patients had relapsed CLL and more than one-third were refractory to their last treatment. Venetoclax is an investigational, first-in-class, B-cell lymphoma-2 (BCL-2) inhibitor being developed and commercialized by AbbVie and Genentech and Roche.

In arm A of the M12-175 study, venetoclax had an overall response rate of 79 percent (n=92/116) and complete response in 20 percent of patients. Serious adverse events (AEs) occurring in ≥ 2 percent of patients were febrile neutropenia, pneumonia, immune thrombocytopenia, tumor lysis syndrome, diarrhea, fluid overload, hyperglycemia, prostate cancer, pyrexia, upper respiratory tract infection, and viral upper respiratory tract infection. Grade 3 or 4 AEs occurring in ≥ 2 percentof patients were diarrhea, nausea, neutropenia, fatigue, anemia, thrombocytopenia, vomiting and hyperglycemia.

CLL is a typically slow-progressing cancer of the bone marrow and blood in which the bone marrow makes too many lymphocytes, a type of white blood cell.  Approximately 3-10 percent of CLL patients have 17p deletion at diagnosis. The 17p deletion mutation is a genomic alteration in which a part of chromosome 17 is absent.

Venetoclax is an investigational oral BCL-2 inhibitor being evaluated for the treatment of patients with various cancer types. The BCL-2 protein prevents apoptosis of some cells, including lymphocytes, and can be over expressed in some cancer types. Venetoclax is designed to selectively inhibit the function of the BCL-2 protein. Venetoclax is being developed in collaboration with Genentech and Roche. Together, the companies are committed to BCL-2 research with venetoclax, which is currently being evaluated in Phase 3 clinical trials for the treatment of relapsed/refractory CLL, along with studies in several other cancers. Venetoclax is an investigational compound and its safety and efficacy have not been evaluated by the FDA or any other health authority.