Norwegian oncology biopharmaceutical company BerGenBio has presented results from preclinical studies on the agent BGB324 which suggest that the cancer therapy may be effective as new treatment for patients with drug resistant Chronic Myeloid Leukemia (CML).
The data was presented at the Annual Meeting of the American Society of Hematology (ASH), which took place on December 7-10, 2013. According to BerGenBio the results suggest that BGB324 may be effective as monotherapy in treating patients with drug-resistant CML as a result of exposure to Abelson kinase (Abl) inhibitors such as imatinib, nilotinib and dasatinib, (Novartis’s Gleevec and Tasigna, and Bristol Myer Squibb’s Sprycel) which are widely used as first line therapy in patients. Long term therapy with these agents can result in the development of resistance and new mutations. Overexpression of the Axl tyrosine kinase is known to confer resistance to treatment with imatinib.
BerGenBio states that treatment with BGB324 was effective in inducing programmed cell death in CML stem cells located in the marrow. The results also revealed that treatment with BGB324 was effective in treating animals infected with CML cells expressing the T315I mutation of ABL which is resistant to treatment with currently approved drugs. The data further underscores the potential of BGB324 in addressing the spread of leukemias and other resistant cancers whose biology is driven by Axl expression. BGB324 is a first-in-class, highly selective small molecule inhibitor of the Axl receptor tyrosine kinase. Preclinical in vivo studies have shown that BGB324 has both single agent activity in leukemia and solid tumors and is very effective in preventing and reversing acquired resistance to existing therapies including cytotoxics, protein kinase inhibitors and other targeted therapies. It is the only selective Axl inhibitor in clinical development having recently completed a phase Ia clinical trial. Phase Ib clinical trials are planned in acute myeloid leukemia and non-small cell lung cancer in 2014.
The results are based on work conducted by Dr. Sonja Loges’ group from the Department of Hematology, Oncology and Bone Marrow Transplantation with Section Pneumology and from the Institute of Tumor Biology, University Medical Center Hamburg-Eppendorf.