EU Approves AbbVie/Roche’s Venclyxto Plus Hypomethylating Agent as First-Line Treatment for Acute Myeloid Leukemia, Demonstrating Significant Overall Survival Benefit

May 26, 2021 /BioonBIOON/ -- AbbVie recently announced that the European Commission (EC) has approved Venclyxto (venetoclax) in combination with hypomethylating agents (azacitidine or decitabine) for the treatment of newlyDiagnosis, ineligible for intensive chemotherapy, acute myeloidLeukemia(AML) adult patients.

This approval marks the third indication expansion for Venclexta in the European Union.The regimen of Venclexta in combination with hypomethylating agents will provide a meaningful improvement over existing treatment options, particularly for elderly patients with AML who typically have a poor prognosis and are often ineligible for intensive chemotherapy due to age and comorbidities.

Venetoclax is a first-in-class, oral, selective B-cell lymphoma-2 (BCL-2) inhibitor., co-developed by AbbVie and Roche, with both parties jointly responsible for commercialization in the U.S. market (brand name: Venclexta), while AbbVie is responsible for commercialization in markets outside the U.S. (brand name: Venclyxto).

In the United States, venetoclax (brand name: Venclexta) received in October 2020FDAApproved, in combination with hypomethylating agents (azacitidine [AZA] or decitabine [DAC]) or low-dose cytarabine (LDAC), for first-line treatment of new-Diagnosisfor two categories of adult patients with AML, specifically: (1) elderly AML patients aged ≥75 years; (2) adult AML patients ineligible for intensive induction chemotherapy due to comorbidities. In the United States, Venclexta received in 2018FDAAccelerated approval was granted for the above indications. This approval converts Venclexta’s accelerated approval for the above indications to full approval.

AML (Image source: checkrare.com)

This EU approval is based on the results of the double-blind, placebo-controlled Phase 3 VIALE-A (M15-656) study and the open-label, non-randomized, multicenter Phase 1b M14-358 study.

VIALE-A Study in NewDiagnosisconducted in adult patients with AML who were ineligible for intensive chemotherapy, compared the efficacy and safety of the placebo + azacitidine (AZA, a hypomethylating agent) regimen and the venetoclax + azacitidine regimen. The results showed that the study met its primary and secondary endpoints: compared with placebo + azacitidine, the venetoclax + azacitidine regimen significantly prolonged overall survival (OS) and substantially increased the complete remission rate and the complete remission with incomplete hematologic recovery (CR/CRi) rate.

Specific data are as follows: (1) Compared with the azacitidine + placebo group, the venetoclax + azacitidine treatment groupOS significantly prolonged (median OS: 14.7 months vs. 9.6 months)、`34% Reduction in Mortality Risk`(HR=0.66; 95% CI: 0.52-0.85; p<0.001). (2) Compared with the azacitidine + placebo group, the venetoclax + azacitidine treatment groupComposite complete response rate (CR+CRi) was more than double (66.4% vs 28.3%), p < 0.001). (3) The study also met the secondary endpoint of CR+CRh (complete remission + complete remission with partial hematologic recovery): the CR+CRh rate was 64.7% in the venetoclax + azacitidine treatment group and 22.8% in the azacitidine + placebo group. (4) Regarding safety, in this study, the safety profile of venetoclax combined with azacitidine was consistent with the known side effects of both drugs, and adverse events (AEs) were consistent with expectations for the elderly AML population; there was no difference in quality of life between the two treatment groups. The most frequently reported serious adverse events in the venetoclax plus azacitidine group and the placebo plus azacitidine group were febrile neutropenia (30% and 10%), pneumonia (17% and 22%), sepsis (6% and 8%), and bleeding (9% and 6%).

VIALE-A Study Data

Study M14-358 evaluated venetoclax in combination with azacitidine or decitabine for the treatment of newlyDiagnosisefficacy in AML patients. The results showed:

——Patients treated with venetoclax plus azacitidine: the CR rate was 44% and the CR+CRi rate was 71%; the median time from treatment initiation to first CR or CRi was 1.2 months (range: 0.7–7.7 months); among patients who achieved CR or CRi, the median duration of response (DOR) was 21.9 months; the most frequently reported serious adverse events were febrile neutropenia (31%) and pneumonia (26%).

—— In patients treated with venetoclax plus decitabine: the CR rate was 55% and the CR+CRi rate was 74%; the median time from treatment initiation to first CR or CRi was 1.9 months (range: 0.9–5.4 months); among patients who achieved CR or CRi, the median duration of response (DOR) was 15 months; the most frequently reported serious adverse events were febrile neutropenia (42%), pneumonia (29%), bacteremia (16%), and sepsis (6%).

Acute myeloid leukemia (AML) is one of the most aggressive and difficult-to-treat blood cancers, with a very low survival rate and highly limited treatment options; only about 28% of patients survive for five years or longer. AML originates in the bone marrow, leading to an increased number of abnormal white blood cells in the blood and bone marrow. AML typically progresses rapidly, but not all patients are eligible for intensive chemotherapy. Age and comorbidities are common factors that limit the use of intensive chemotherapy.

The active pharmaceutical ingredient of Venclexta/Venclyxto is venetoclax, an oral B-cell lymphoma 2 (BCL-2) inhibitor. The BCL-2 protein inApoptosis(programmed cell death), plays an important role in..., prevents the apoptosis of certain cells (including lymphocytes), and is overexpressed in certain types of cancer, 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 to achieve therapeutic effects.Tumorthe purpose.

Venetoclax was co-developed by AbbVie and Roche, with both companies jointly responsible for its commercialization in the U.S. market (brand name: Venclexta), and AbbVie responsible for commercialization outside the U.S. (brand name: Venclyxto). In the United States, venetoclax has beenFDAGranted 5 Breakthrough Therapy Designations (BTD), one for first-line treatment of CLL, two for relapsed or refractory CLL, and two for first-line treatment of acute myeloid leukemia (AML).

To date, Venclexta/Venclyxto has been approved for marketing in over 80 countries worldwide for the treatment of adults with chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL), and acute myeloid leukemia (AML). Currently, AbbVie and Roche are conducting a large-scale clinical program to investigate venetoclax monotherapy and combination therapies for various types of blood cancers, including CLL, AML, non-Hodgkin lymphoma (NHL), diffuse large B-cell lymphoma (DLBCL), and multiple myeloma (MM), among others. (Bioon.com)

Source: AbbVie Receives European Commissionapproval of VENCLYXTO® (venetoclax) in Combination with a Hypomethylating Agent for Patients with Newly Diagnosed Acute Myeloid Leukemia Who Are Ineligible for Intensive Chemotherapy