BioLineRx has announced that Prof. Arnon Nagler, Director of the Hematology Division and Bone Marrow Transplantation Center at Sheba Medical Center, Israel, has received final regulatory approval to evaluate BioLineRx’s BL-8040 as a treatment for chronic myeloid leukemia (CML) in a Phase 1/2 clinical study.
BioLineRx is currently developing BL-8040 in a Phase 2 study for treating acute myeloid leukemia (AML), and in a Phase 1 study for stem cell mobilization, as a pre-treatment for stem cell transplantation. The Company has received orphan drug designation for both these indications.
Dr. Kinneret Savitsky, Chief Executive Officer of BioLineRx, stated, "We are extremely pleased that our promising and versatile therapeutic candidate is ready to commence a Phase 1/2 clinical trial for a third indication, namely CML. Prof. Nagler’s decision to pursue BL-8040 for CML in an independent clinical study is a testament to the potential he sees in our molecule for treating hematologic cancers. Each of these indications stands to benefit from the two main characteristics of BL-8040 - its ability to mobilize cells from the bone marrow into the peripheral blood system, and its ability to induce cancer cell death directly."
CML is a cancer of white blood cells that is driven by a constitutively active oncogenic tyrosine kinase. The main treatment today is with tyrosine kinase inhibitors, such as Imatinib (Gleevec), but about 15% of patients do not have an optimal response to the drug, and 40% eventually develop resistance to the drug. In addition, treatment with Gleevec does not always prevent recurrence of the disease, presumably due to the survival of dormant, tumorigenic stem cells in the bone marrow.
The study is designed as a Phase 1/2, randomized, dose-escalation study to assess the combination of BL-8040 with standard-of-care Imatinib for improving the response of CML patients in the first chronic phase of the disease who have achieved a less than optimal response with Imatinib alone.
Primary endpoints of the study are the safety and tolerability of BL-8040 in combination with Imatinib, and the secondary endpoints include assessing the efficacy of the combination therapy in achieving improved cytogenetic and molecular response in CML patients. The study will be performed at the Sheba Medical Center, and will include up to 40 patients.
“The bone marrow has a protective effect on CML stem cells, and enables them to evade eradication by existing drugs. Preclinical data have shown that BL-8040 efficiently synergizes with Imatinib in-vitro1 and in-vivo, overcoming the protective effect of the bone marrow, and we therefore hope that the combination of these two drugs will override drug resistance and suppress residual disease," stated Prof. Nagler.
Prof. Nagler continued, "It is conceivable that adding BL-8040 to Imatinib therapy in CML patients who have not achieved optimal cytogenetic or molecular responses may improve their response to Imatinib by directly inducing apoptosis of the tumor cells and by mobilizing leukemic stem cells from the bone marrow’s protective niches and sensitizing them to Imatinib-induced cell death.”