BCL-2 Inhibitors: Venclaxta showed promising results in leukaemia with 17p deletion
Venclaxta/Venclaxto (Venetoclax) monotherapy has shown high response rates and well tolerated safety profile in patients with relapsed or refractory chronic lymphocytic leukaemia (CLL). Some early data from phase I study has also highlighted its potential in treatment of acute myeloid leukaemia and multiple myeloma. This new data from multiple studies were presented by Roche at the 22nd European Hematology Association (EHA) Annual Congress, 22-25 June, in Madrid.
What is Venetoclax and how it works??
Venetoclax is a BCL-2 inhibitor commercialised by AbbVie and Genentech (a member of the Roche Group) in the United States and by AbbVie outside of the United States. BCL-2 family of anti-apoptotic proteins play a crucial role in regulation of apoptosis. Overexpression of BCL-2 leads to lack of cell death and uncontrolled proliferation of cells thus resulting in hematological malignancies specifically myelomas and lymphomas. Such hematological malignancies are resistant to chemotherapy. Developing small molecules which inhibit BCL-2 family of proteins represents a promising therapeutic strategy to treat such malignancies.
Clinical Updates about Venetoclax
M13-982 Phase II study
: Venetoclax monotherapy responses in 158 patients with relapsed or refractory chronic lymphocytic leukaemia and 17p deletion showed an overall response rate of 77%, complete remission rate of 18% and partial remission rate of 53%. Among 18 patients which were previously given BCR inhibitor, the overall response rate was 61% and the complete remission rate was 11%. Among 158 patients, 27% achieved blood minimal residual disease (MRD) negativity.
M13-365 Phase I study:
This multicenter study is evaluating the safety and tolerability of venetoclax in combination with rituximab in patients with relapsed chronic lymphocytic leukaemia and small lymphocytic leukemia. The patients showed 86% overall response rate and 51% complete response rate. 59% of the patients achieved marrow MRD negativity.
M14-358 Phase Ib study:
In elderly patients with previously untreated acute myeloid leukaemia, venetoclax in combination with decitabine or azacitidine shows an overall response rate of 68%.
M12-901 Phase Ib study:
Patients with relapsed or refractory multiple myeloma when treated with a combination of venetoclax along with bortezomib and dexamethasone showed an overall response rate of 67%.
Competitors of Venetoclax
Venetoclax might face tough competition from Celgene’s Revlimid (lenalidomide), Gilead’s Zydelig (idelalisib) and AbbVie’s own drug Imbruvica (ibrutinib). Revlimid has shown extended progression free survival in CLL and has also been approved by FDA as a maintenance treatment for patients with multiple myeloma following autologous hematopoietic stem cell transplant. Interim results from Phase III study have shown that Zydelig in combination with bendamustine and rituximab improved the progression free survival in patients with relapsed or refractory CLL. According to new data presented at ASCO 2017, Imbruvica has shown a more targeted approach in treatment of CLL as compared to chemotherapy agent chlorambucil.
The new data from the clinical trials confirms the efficacy and tolerability of venetoclax in treatment of relapsed or refractory chronic lymphocytic leukaemia. This therapy is quite promising for CLL patients with 17p deletion who respond less well to standard chemotherapy and have a shorter overall survival. Venetoclax is also being evaluated in acute myeloid leukaemia and multiple myeloma which will further broaden the treatment options for such hard-to-treat blood cancers.