February 05, 2020 / BIOON -- Roche recently announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has issued a positive opinion, recommending the approval of Venclyxto (venetoclax) in combination with Gazyvaro (obinutuzumab) as first-line treatment for adult patients with chronic lymphocytic leukemia (CLL). The CHMP’s opinion will now be submitted to the European Commission (EC) for review, which is expected to make a final decision within the coming months.
Dr. Levi Garraway, Chief Medical Officer and Global Head of Product Development at Roche, stated: “CLL is the most common type of leukemia in adults. In recent years, although progress has been made in the treatment of CLL, many patients cannot tolerate the side effects of chemotherapy-containing regimens. We are pleased that the CHMP has recognized the therapeutic potential of Venclyxto + Gazyvaro as a fixed-duration, chemotherapy-free regimen in this patient population with this malignancy.”
The CHMP’s positive opinion is based on the results of the pivotal Phase III CLL14 study. This 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 results demonstrated that, compared with Gazyvaro plus chlorambucil (the current standard of care for CLL), 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% (hazard ratio [HR]=0.35; 95% confidence interval [CI]: 0.23–0.53; p<0.0001). These findings were confirmed when PFS was assessed by an independent review committee.
Furthermore, compared with the Gazyvaro plus chlorambucil regimen, the Venclyxto plus Gazyvaro regimen demonstrated higher response rates, including higher minimal residual disease (MRD) negativity rates, indicating that cancer cells were undetectable by specific and highly sensitive assays: (1) peripheral blood MRD negativity rates were 76% for the Venclyxto plus Gazyvaro regimen versus 35% for the Gazyvaro plus chlorambucil regimen; (2) bone marrow MRD negativity rates were 57% for the Venclyxto plus Gazyvaro regimen versus 17% for the Gazyvaro plus chlorambucil regimen.
In patients receiving the Venclyxto + Gazyvaro regimen, the most common adverse events were low white blood cell count (neutropenia), diarrhea, and upper respiratory tract infections.
In May 2019, based on the data from the CLL14 study, the U.S. FDA approved the venetoclax + obinutuzumab combination regimen through the Real-Time Oncology Review (RTOR) pilot program (Venclexta+Gazyva), adult patients with CLL and comorbidities in the first-line treatment setting.
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. BCL-2 plays a critical role in apoptosis (programmed cell death) by preventing the apoptosis of certain cells, including lymphocytes. It is overexpressed in certain types of cancer and is associated with the development of drug resistance. Venetoclax is designed to selectively inhibit BCL-2 function, restore cellular signaling pathways, and induce cancer cell self-destruction, thereby achieving antitumor therapeutic effects.
Venetoclax was co-developed by AbbVie and Roche. The two companies jointly commercialize the drug in the US market under the brand name Venclexta, while AbbVie is responsible for its commercialization in markets outside the US under the brand name Venclyxto. In the US, venetoclax has been granted five Breakthrough Therapy Designations (BTD) by the FDA: one for first-line treatment of chronic lymphocytic leukemia (CLL), two for relapsed or refractory CLL, and two for first-line treatment of acute myeloid leukemia (AML).
Currently, both parties are conducting a large-scale clinical program to investigate venetoclax monotherapy and combination therapies 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, capable of directly inducing B cell death. Obinutuzumab is designed to enhance antibody-dependent cellular cytotoxicity (ADCC) and direct cell death induction. The brand name for obinutuzumab in the United States is Gazyva, while in Europe it is known as Gazyvaro. (Bioon.com)
