On August 7, 2018 BioLineRx Ltd. (NASDAQ: BLRX) (TASE: BLRX), a clinical-stage biopharmaceutical company focused on oncology and immunology, reported the positive results from the lead-in period of the GENESIS trial, a double-blind, placebo-controlled Phase 3 trial comparing BL-8040 in combination with granulocyte colony-stimulating factor (G-CSF), to G-CSF alone, for the mobilization of hematopoietic stem cells (HSCs) used for autologous transplantation in multiple myeloma patients (Press release, BioLineRx, AUG 7, 2018, View Source;p=RssLanding&cat=news&id=2362414 [SID1234528751]).
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The open-label, single-arm, lead-in period of the study was designed to include up to 30 patients, with Data Monitoring Committee (DMC) review after completion of approximately 10, 20 and 30 patients, in order to assess safety and efficacy following treatment with BL-8040 plus G-CSF. Results of the first 11 patients show that BL-8040 in combination with standard G-CSF treatment is safe and tolerable. In addition, the data show that 9/11 patients (82%) reached the primary endpoint threshold of ≥ 6×106 CD34 cells/kg with only one dose of BL-8040 and in up to 2 apheresis sessions. Furthermore, 7/11 patients (64%) reached the threshold of ≥ 6×106 CD34 cells/kg in a single apheresis session only. These data demonstrate the potential of BL-8040 treatment to reduce the number of administrations and apheresis sessions, as well as hospitalization costs, related to the preparation of multiple myeloma patients for autologous HSC transplantation.
"Autologous HSC transplantation following high-dose chemotherapy has significantly improved outcomes for multiple myeloma patients," said Dr. John F. DiPersio, Chief, Division of Oncology at the Washington University School of Medicine, and lead investigator of the study. "Current practice involves mobilizing HSCs from the bone marrow to the peripheral blood, after which the cells are collected by apheresis. Results so far show that mobilizing HSCs with a single BL-8040 dose combined with G-CSF is not only safe and tolerable, but also demonstrates robust efficacy regarding the number of collected cells, and may reduce the number of required apheresis sessions to a single session in the majority of patients. This is a very encouraging result that, if corroborated in the placebo-controlled part of the trial, will be of great value to patients as well as to the medical community. I am looking forward to participating in the trial and to potentially improving the quality of treatment available to multiple myeloma patients."
"We are extremely encouraged by these results. Based on the robust data received from the first 11 patients, the DMC issued a positive recommendation to stop the lead-in part of the study and move immediately to the randomized placebo-controlled part of the study," stated Philip Serlin, Chief Executive Officer of BioLineRx. "This is the first Phase 3 trial for our lead BL-8040 program, and as such, it is an important milestone in BL-8040’s comprehensive development plan. We look forward to the top-line results from the randomized, double-blind, placebo-controlled part of the study, which are expected in 2020."
About the GENESIS Study
The GENESIS study is a Phase 3, randomized, double-blind, placebo-controlled, multicenter study, evaluating the safety, tolerability and efficacy of BL-8040 in combination with G-CSF, compared to placebo and G-CSF, for the mobilization of CD34 HSCs for autologous transplantation in multiple myeloma patients. The placebo-controlled part is designed to include 177 patients in more than 25 centers. Treatment will include 5 days of G-CSF, with a single dose of BL-8040 or placebo on day 4 with the option to expand treatment to up to 8 days of G-CSF and up to 2 days of BL-8040. Apheresis for collection of CD34 cells will be performed on day 5. An additional 3 apheresis sessions may be conducted if needed in order to reach the goal of ≥ 6×106 mobilized CD34 cells/kg.
The primary objective of the study is to demonstrate the superiority of a single dose of BL-8040 in combination with G-CSF, over placebo and G-CSF, in the mobilization of ≥ 6×106 CD34 cells/kg in up to 2 apheresis sessions, in preparation for autologous stem cell transplantation in multiple myeloma patients. Secondary objectives include time to engraftment of neutrophils and platelets, durability of the engraftment, as well as safety and other efficacy parameters.
About BL-8040
BL-8040 is a short synthetic peptide for stem cell mobilization and for treatment of hematological malignancies and solid tumors. It functions as a high-affinity best-in-class antagonist for CXCR4, a chemokine receptor that is directly involved in the retention of stems cells in the bone marrow, as well as tumor progression, angiogenesis, metastasis and cell survival. CXCR4 is over-expressed in more than 70% of human cancers and its expression often correlates with disease severity.
HSCs express CXCR4 and are retained in the protective bone marrow niche via binding to CXCL12 (also known as SDF-1). Blocking of the CXCR4-SDF1 interaction by BL-8040 leads to the mobilization of HSCs into the peripheral blood. In a number of clinical and pre-clinical studies, BL-8040 has shown robust mobilization of HSCs.
Furthermore, BL-8040 induce mobilization of leukemic cells and immune-cells from the bone marrow, thereby sensitizing leukemic cells to chemo- and bio-based anti-cancer therapy, as well as a direct anti-cancer effect by inducing cell death (apoptosis). BL-8040 was licensed by BioLineRx from Biokine Therapeutics and was previously developed under the name BKT-140.