AbbVie and Roche’s Venclexta + Gazyva Receives Health Canada Approval as First Chemotherapy-Free, Fixed-Duration First-Line Treatment for CLL

May 07, 2020 /BioValleyBIOON/ -- AbbVie recently announced that Health Canada has approved the targeted anticancer drug Venclexta (venetoclax) in combination with Gazyva (obinutuzumab) for the treatment of previously untreated chronic lymphocyticLeukemia(CLL) adult patients. The regimen combines 6 cycles of Gazyva (28 days per cycle) and 12 cycles of Venclexta.

This approval is based on data from the pivotal Phase III clinical study CLL14: Compared with patients receiving the standard-of-care regimen of chlorambucil plus obinutuzumab (abbreviated as CO), those treated for one year with the venetoclax plus obinutuzumab regimen (abbreviated as VO) demonstrated a clinically and statistically significant prolongation in progression-free survival (PFS) and achieved a higher proportion of undetectable minimal residual disease (MRD).

It is worth noting that Venclexta + Gazyva is the first chemotherapy-free, fixed-duration combination regimen approved by Health Canada for the first-line treatment of CLL. In the United States, this regimen was approved in May 2019FDAApproved for the first-line treatment of adult patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL).

CLL14 is a prospective, multicenter, open-label, randomized study conducted in collaboration with the German CLL Study Group (DCLLSG), designed to evaluate the efficacy and safety of a 12-month fixed-duration, chemotherapy-free combination regimen VO versus the standard-of-care regimen CO as first-line treatment for patients with CLL and comorbidities. A total of 445 patients were enrolled in the study, all of whom were previously untreated according to the International Workshop on Chronic Lymphocytic Leukemia (iwCLL) criteria. In the study, patients received treatment for a fixed duration of 12 months. The primary endpoint was investigator-assessed progression-free survival (PFS) according to iwCLL criteria. Secondary endpoints included PFS assessed by an independent review committee (IRC), minimal residual disease (MRD) status, overall response rate (ORR), complete response rate (CR), overall survival, duration of response, event-free survival, time to next CLL treatment, and safety.

With a median follow-up of 28 months, the results showed: (1) Compared with the CO regimen group, the VO regimen group demonstrated significantly prolonged progression-free survival (PFS) and a 65% significant reduction in the risk of disease progression or death (investigator-assessed PFS: HR=0.35, 95% CI: 0.23–0.53, p<0.001; IRC-assessed PFS: HR=0.33, 95% CI: 0.22–0.51, p<0.001). At 2 years (i.e., 1 year after treatment cessation), a higher proportion of patients in the VO regimen group remained progression-free (88.2% vs. 64.1%), and the median investigator-assessed PFS had not been reached. (2) Compared with the CO regimen group, the VO regimen group demonstrated consistent clinical benefits across all secondary endpoints, including overall response rate (ORR) (84.7% vs. 71.3%, p<0.001) and complete response (CR) with at least partial hematologic recovery (49.5% vs. 23.1%, p<0.001). (3) Three months after treatment initiation, a higher proportion of patients in the VO regimen group achieved bone marrow MRD negativity (56.9% vs. 17.1%, p<0.001) and peripheral blood MRD negativity (75.5% vs. 35.2%, p<0.001) compared with the CO regimen group. MRD negativity was defined as fewer than one CLL cell per 10,000 white blood cells. (4) The safety profile of the VO regimen was consistent with the known safety profiles of the individual drugs, and no new safety signals were identified with the combination therapy. The incidence of common grade 3/4 adverse events in the VO regimen group and the VC regimen group was comparable, specifically for low white blood cell count (52.8% vs. 48.1%) and infection (17.5% vs. 15.0%).

Chronic lymphocytic leukemia (CLL) is a slow-growing type of leukemia and one of the most common forms of leukemia in adults, characterized by the presence of large numbers of immature lymphocytes in the blood and bone marrow. CLL accounts for approximately one-third of newly diagnosed leukemia cases.

The active pharmaceutical ingredient of Venclexta is venetoclax, an oral B-cell lymphoma-2 (BCL-2) inhibitor. BCL-2 plays a role inApoptosis(plays an important role in programmed cell death), can inhibit apoptosis of certain cells (including lymphocytes), and is overexpressed in certain types of cancer, contributing to the development of drug resistance. Venetoclax is designed to selectively inhibit BCL-2 function, restore cellular communication pathways, and induce cancer cell self-destruction for therapeutic effect.Tumorof the purpose.

Venclexta was co-developed by AbbVie and Roche, with both parties jointly responsible for its commercialization in the U.S. market, while AbbVie handles commercialization in markets outside the United States (under the brand name Venclyxto). Currently, the two companies are conducting a large-scale clinical program to investigate venetoclax as monotherapy and in combination regimens for the treatment of various types of hematologic malignancies, including chronic lymphocytic leukemia (CLL), non-Hodgkin lymphoma (NHL), diffuse large B-cell lymphoma (DLBCL), acute myeloid leukemia (AML), and multiple myeloma (MM).

The active pharmaceutical ingredient of Gazyva is obinutuzumab, the first glycosylated type II anti-CD20 monoclonal antibody. It targets CD20 molecules on the surface of B cells and can directly induce B-cell death. Obinutuzumab is designed to enhance antibody-dependent cellular cytotoxicity (ADCC) and direct cell death induction. Obinutuzumab is marketed under the brand name Gazyva in the United States and Gazyvaro in Europe. (Bioon.com)

Original Source: AbbVie Receives Health Canadaapproval for the Combination of VENCLEXTA (venetoclax) with Obinutuzumab for Patients with Previously Untreated Chronic Lymphocytic Leukemia