AbbVie and Roche’s Chemotherapy-Free Venclyxto + Gazyvaro Fixed-Duration Regimen Approved by European Commission for First-Line Treatment of CLL

March 13, 2020/Bio ValleyBIOON/-- AbbVie recently announced that the European Commission (EC) has approved Venclyxto (venetoclax) in combination with Gazyvaro (obinutuzumab) for the treatment of previously untreated chronic lymphocyticLeukemia( CLL ) adult patients. This approval applies to the 27 member states of the European Union, as well as Iceland, Liechtenstein, Norway, and the United Kingdom. Notably, this marks the third regulatory approval for Venclyxto in the European Union. Previously, the drug had been approved: (1) in combination with rituximab for the treatment of adult patients with CLL who have received at least one prior therapy; (2) as monotherapy for the treatment of adult patients with CLL, with or without 17p deletion or TP53 mutation, who are ineligible for or have failed treatment with a B-cell receptor pathway inhibitor.

CLL is the most common type of leukemia in adults. In recent years, despite advances in treatment, many patients cannot tolerate the side effects of chemotherapy-containing regimens. Venclyxto + Gazyvaro, as a fixed-duration, chemotherapy-free regimen, will provide an important treatment option for CLL patients, who can achieve deep remission and sustained progression-free survival benefits, while also gaining the additional advantage of a limited treatment duration.

This approval is based on the results of the pivotal Phase III CLL14 study. The study evaluated a 12-month, fixed-duration regimen of Venclyxto plus Gazyvaro versus Gazyvaro plus chlorambucil as first-line treatment for adult patients with chronic lymphocytic leukemia (CLL) and comorbidities. The primary analysis (median follow-up: 28 months) demonstrated that the Venclyxto plus Gazyvaro regimen significantly reduced the risk of disease progression or death (progression-free survival [PFS], as assessed by study investigators) by 65% compared with Gazyvaro plus chlorambucil (the current standard of care for CLL) (HR=0.35; 95% CI: 0.23–0.53; p<0.0001; median PFS was not reached in either group).

In the latest efficacy analysis of the CLL14 study (median follow-up: 40 months), the median progression-free survival (PFS) was 35.6 months (95% CI: 33.7, 40.7) in the Gazyvaro plus chlorambucil group, whereas the median PFS was not reached in the Venclyxto plus Gazyvaro group, representing a 69% reduction in the risk of disease progression or death (HR=0.31; 95% CI: 0.22, 0.44). The estimated 36-month PFS rate was 81.9% (95% CI: 76.5, 87.3) in the Venclyxto plus Gazyvaro group and 49.5% (95% CI: 42.4, 56.6) in the Gazyvaro plus chlorambucil group.

Furthermore, after one year of treatment, patients in the Venclyxto + Gazyvaro group experienced deeper responses, with higher rates of minimal residual disease (MRD) negativity and complete response (CR), compared to the Gazyvaro + chlorambucil group. In this study, adverse events (AEs) were consistent with the known safety profiles of Venclyxto and Gazyvaro, respectively.

In May 2019, based on the CLL14 study data, the United StatesFDAThrough real-timeTumorThe Real-Time Oncology Review (RTOR) pilot program approved the venetoclax + obinutuzumab combination regimen (Venclexta + Gazyva) for first-line treatment of adult patients with chronic lymphocytic leukemia (CLL) and comorbidities.

CLL is a slow-growing type of leukemia 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.

Venetoclax (Venclexta/Venclyxto) is an oral B-cell lymphoma-2 (BCL-2) inhibitor, with BCL-2 playing a role inApoptosis(programmed cell death) plays an important role, can inhibit apoptosis of some cells (including lymphocytes), and is overexpressed in certain types of cancer, associated with the development of drug resistance. Venetoclax is designed to selectively inhibit the function of BCL-2, restore cellular communication systems, allow cancer cells to self-destruct, and achieve therapeutic effects.Tumorthe purpose.

Venetoclax was co-developed by AbbVie and Roche. The two companies jointly commercialize the drug in the U.S. market under the brand name Venclexta, while AbbVie is responsible for its commercialization in markets outside the U.S. under the brand name Venclyxto. Currently, both parties 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).

Obinutuzumab (Gazyva/Gazyvaro) is a product developed by Roche. It is the first glycosylated type II anti-CD20 monoclonal antibody that 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 European Commissionapproval of VENCLYXTO Combination Regimen for Patients with Previously-Untreated Chronic Lymphocytic Leukemia