Roche / AbbVie Venclexta Combination Therapy Phase III Study Is Successful!

- May 07, 2020-


Roche and AbbVie recently announced that the Phase III VIALE-A study reached the common primary endpoint of overall survival (OS) and composite complete response rate (CR + CRi). The study was conducted in patients with acute myeloid leukemia (AM) who had not previously received treatment and were not eligible for intensive chemotherapy. The results showed that patients treated with azacitidine (AZA, a hypomethylating agent) monotherapy In contrast, patients receiving combination therapy with Venclexta / Venclyxto (venetoclax) and azacitidine achieved statistically significant improvements in overall survival (OS). In this study, the safety of the combination of Venclexta / Venclyxto and azacitidine was consistent with the known safety of these drugs.


Levi Garraway, MD, Roche ’s chief medical officer and head of global product development, said: “At present, AML is still a challenging blood cancer. Among patients who cannot tolerate intensive chemotherapy due to age or underlying health status, the survival rate is particularly high. Low. These data confirm that the combination therapy based on Venclexta / Venclyxto can bring therapeutic benefits to patients, and we look forward to discussing the results with regulatory agencies. "

Venclexta

Venclexta / Venclyxto is a first-in-class, oral, selective B-cell lymphoma factor-2 (BCL-2) inhibitor, developed by AbbVie and Roche, and is jointly responsible for the commercialization of the US market (trade name: Venclexta) , AbbVie is responsible for the commercialization of markets outside the United States (trade name: Venclyxto). As of now, in terms of U.S. regulation, Venetoclax has been awarded 5 Breakthrough Drug Qualifications (BTD): 1 BTD has been granted first-line treatment for chronic lymphocytic leukemia (CLL), and 2 BTD has been granted to treat relapsed or refractory CLL and 2 BTDs were granted first-line treatment for AML.


Previously, Venclexta has received accelerated approval from the US FDA in combination with low methylation agents (azacitidine (AZA) or decitabine [decitabine, DAC]) or low-dose cytarabine (LDAC), first-line treatment Newly diagnosed adult patients with type 2 AML are: (1) elderly AML patients aged 75 years and over; (2) adult patients with AML who are not suitable for intensive induction chemotherapy due to the presence of other diseases.


This accelerated approval is based on the response rate data of 2 clinical studies (M14-358 and M14-387). The two studies were conducted in newly diagnosed AML patients, including those who were not eligible for intensive induction chemotherapy. In the M14-358 study, the complete remission rate (CR) of the Venclexta + AZA program was 37%, the complete solution rate (CRh) of the partial recovery of the blood cell count was 24%, the CR of the Venclexta + DAC program was 54%, and the CRh was 8 %. In the M14-387 study, the Venclexta + LDAC scheme had a CR of 21% and CRh of 21%.


Continued approval of this indication depends on the verification and description of clinical benefits in confirmatory studies. Currently, Roche and AbbVie are conducting two confirmatory phase III studies VIALE-A (M15-656, NCT02993523) and VIALE-C (M16-043, NCT03069352).


At the end of February this year, both parties announced the latest results from the VIALE-C study. The study was conducted in newly diagnosed AML patients who did not qualify for intensive chemotherapy. The results showed that the study did not reach the primary endpoint of significant improvement in OS: compared with the placebo + LDAC treatment group, the risk of death was reduced by 25% in the venetoclax + LDAC treatment group (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 in the venetoclax + LDAC treatment group was 7.2 months, and the median OS in the placebo + LDAC treatment group was 4.1 months. Post-hoc analysis after an additional 6 months of follow-up showed that the median OS in the venetoclax + LDAC treatment group was 8.4 months, and the median OS in the placebo + LDAC treatment group was 4.1 months (HR = 0.70 [95% CI: 0.50-0.99] ).


However, in terms of the secondary endpoint, compared with the placebo + LDAC treatment group, the complete remission rate of the venetoclax + LDAC treatment group was significantly improved (CR: 27.3% vs 7.4%), complete remission or complete remission with incomplete recovery of blood cell count was significant Improvement (CR + CRi: 47.6% vs 13.2%), complete remission or complete remission of partial hematological recovery (CR + CRh: 46.9% vs 14.7%), CR + CRi significantly increased when starting the second course of treatment (34.3% vs 2.9%), all p values were <0.001.


Detailed data of the VIALE-A study and VIALE-C study will be announced at the upcoming medical conference. At present, the indications for the first-line treatment of AML with Venclexta / Venclyxto remain unchanged.

Venclexta

Acute myeloid leukemia (AML) is one of the most aggressive and difficult to treat blood cancers, with a low survival rate and very limited treatment options. AML is formed in the bone marrow, resulting in an increase in the number of abnormal white blood cells in the blood and bone marrow. AML usually deteriorates quickly, but not all patients are eligible for intensive chemotherapy. Age and comorbidities are common factors limiting intensive chemotherapy. Only about 28% of patients can survive for 5 years and get longer.


Venclexta / Venclyxto's active pharmaceutical ingredient is Venetoclax, which is an oral B-cell lymphoma factor-2 (BCL-2) inhibitor. BCL-2 protein plays an important role in apoptosis (programmed cell death). Preventing the apoptosis of some cells (including lymphocytes) and overexpressing them in certain types of cancer is related to the development of drug resistance. Venetoclax aims to selectively inhibit the function of BCL-2, restore the cell's communication system, and allow cancer cells to self-destruct to achieve the purpose of treating tumors. As of now, Venetoclax has been approved for marketing in more than 50 countries around the world and is used for the treatment of chronic lymphocytic leukemia (CLL), small cell lymphoma (SLL), and acute myeloid leukemia (AML) in adults.


Currently, Roche and AbbVie are conducting a large-scale clinical project to investigate Venetoclax monotherapy and combination therapy for the treatment of multiple types of blood cancer, including CLL, AML, Hodgkin lymphoma (NHL), and diffuse large B-cell lymphoma (DLBCL ) And multiple myeloma (MM), etc.