VENCLEXTA (venetoclax) Receives FDA Full Approval for First-Line Treatment of Acute Myeloid Leukemia in Adults Ineligible for Intensive Chemotherapy
Oct 21, 2020 09:20
CST Updated
09:20
AbbVie
Innovative Drug Developer
Roche
Oncology Drug Research, Development, and Manufacturing
FDA
U.S. Food and Drug Administration
October 21, 2020 /BioValleyBIOON/ -- AbbVie recently announced that the U.S. Food and Drug Administration (FDA) has approved the anticancer drug Venclexta (venetoclax) in combination with azacitidine (AZA), decitabine, or low-dose cytarabine (LDAC) for the treatment of newlyDiagnosisAcute MyeloidLeukemia(AML) adult patients, specifically: patients aged ≥75 years, or those excluded from receiving intensive induction chemotherapy due to comorbidities. In the United States, Venclexta was approved in 2018FDAAccelerated approval was granted for the aforementioned indications. This approval converts the aforementioned indications for Venclexta from accelerated approval to full approval.
Acute Myeloid Leukemia (AML) is one of the most aggressive and difficult-to-treat blood cancers, characterized by low survival rates and very limited treatment options. AML originates in the bone marrow, leading to an increased number of abnormal white blood cells in the blood and bone marrow. The disease typically progresses rapidly; however, not all patients are eligible for intensive chemotherapy. Age and comorbidities are common factors that limit the use of intensive chemotherapy. Only approximately 28% of patients survive for five years or longer.
Venclexta/Venclyxto is a first-in-class, oral, selective B-cell lymphoma-2 (BCL-2) inhibitor co-developed by AbbVie and Roche. The two companies are jointly responsible for its commercialization 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).
This approval was supported by data from the Phase 3 VIALE-A (M5-656) and VIALE-C (M16-043) studies, as well as updated data from the Phase 1b M14-358 and Phase 1/2 M14-387 studies.
The VIALE-A study in previously untreated patients who are ineligible for or intolerant to conventional intensive chemotherapy, newDiagnosisconducted in AML patients, comparing the efficacy and safety of the placebo + azacitidine (AZA, a hypomethylating agent) regimen versus the venetoclax + azacitidine regimen. The results showed that, compared with placebo + azacitidine, the venetoclax + azacitidine regimen significantly prolonged overall survival (OS).
The specific efficacy data were as follows: (1) Compared with the azacitidine + placebo group, the venetoclax + azacitidine treatment group demonstrated a significantly prolonged overall survival (OS) (median OS: 14.7 months vs. 9.6 months) and a 34% reduction in the risk of death (HR=0.66; 95% CI: 0.52–0.85; p<0.001). (2) Compared with the azacitidine + placebo group, the composite complete response rate (CR+CRi) in the venetoclax + azacitidine treatment group was more than doubled (66.4% vs. 28.3%, p<0.001). Furthermore, the study also met the secondary endpoint of CR+CRh (complete response + complete response with partial hematologic recovery): the CR+CRh rate was 64.7% in the venetoclax + azacitidine treatment group versus 22.8% in the azacitidine + placebo group.
The VIALE-C study was conducted in patients with newly diagnosed acute myeloid leukemia (AML) who were ineligible for intensive chemotherapy. In this study, patients were randomized to compare the efficacy and safety of venetoclax plus low-dose cytarabine (LDAC) versus placebo plus LDAC (n=68). The primary efficacy endpoint was overall survival (OS) compared between the two groups.
The results showed that the study did not meet its primary endpoint of significantly improving OS: compared with the placebo + LDAC group, the venetoclax + LDAC group had a 25% reduction in the risk of death (HR = 0.75 [95% CI: 0.52–1.07], p = 0.11). In the preliminary analysis (median follow-up of 12 months), the median OS was 7.2 months in the venetoclax + LDAC group versus 4.1 months in the placebo + LDAC group. Regarding secondary endpoints, compared with the placebo + LDAC group, the venetoclax + LDAC group demonstrated significantly higher rates of complete response (CR: 27.3% vs. 7.4%), complete response or complete response with incomplete hematologic recovery (CR + CRi: 47.6% vs. 13.2%), complete response or complete response with partial hematologic recovery (CR + CRh: 46.9% vs. 14.7%), and CR + CRi at the start of the second treatment cycle (34.3% vs. 2.9%), with all p-values < 0.001.
The active pharmaceutical ingredient of Venclexta is venetoclax, an oral B-cell lymphoma-2 (BCL-2) inhibitor. The BCL-2 protein plays a role inApoptosis(programmed cell death) and plays an important role in inhibiting 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 the function of BCL-2, restore cellular communication systems, and induce cancer cell self-destruction for therapeutic purposes.Tumorpurpose. To date, venetoclax has been approved for marketing in multiple countries worldwide for the treatment of chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL), and acute myeloid leukemia (AML) in adults.
In the United States, venetoclax has beenFDAFive Breakthrough Therapy Designations (BTDs) have been granted: one BTD for first-line treatment of chronic lymphocytic leukemia (CLL), two BTDs for the treatment of relapsed or refractory CLL, and two BTDs for first-line treatment of acute myeloid leukemia (AML). Currently, Roche and AbbVie are conducting a large-scale clinical program to investigate venetoclax monotherapy and combination therapies for various types of hematologic malignancies, including CLL, AML, non-Hodgkin lymphoma (NHL), diffuse large B-cell lymphoma (DLBCL), and multiple myeloma (MM). (Bioon.com)