BioLineRx touts early BL-8040 results
JERUSALEM—Preclinical studies showed that BL-8040 was efficient, both alone and in combination with the anti-cancer drug Rituximab, in reducing bone marrow metastasis of lymphoma cells and stimulating lymphoma cell death. That therapeutic promise is in part what led BioLineRx to license the compound from Biokine Therapeutics (previously developed under the name BKT-140).
Now that promise is being further borne out as BioLineRx, a clinical-stage biopharmaceutical company whose business model is to identify, in-license and develop promising therapeutic candidates, has published promising initial results for its BL-8040 drug candidate in a Phase 2 clinical trial for patients with relapsed or refractory acute myeloid leukemia (AML). The early results show that BL-8040, as a stand-alone therapy and in combination with high-dose Cytarabine (Ara-C), is safe at all doses tested to date, and triggers substantial mobilization of cancer cells from the bone marrow to the peripheral blood, thereby increasing the vulnerability of the cells to chemotherapy treatment.
In addition, signs of robust apoptosis (cell death) of cancer cells were observed following administration of the higher doses tested to date. The study has not yet reached the highest planned doses, suggesting that a strengthening of BL-8040’s effects may be observed in future dosing cohorts.
The Phase 2 trial is a multicenter, open-label study under an IND, and is designed to evaluate the safety and efficacy of repeated escalating doses of BL-8040 in adult patients with relapsed or refractory AML. The primary endpoints of the study are to assess the safety and tolerability of BL-8040. Secondary endpoints include the pharmacokinetic profile of the drug and an efficacy evaluation, indicated by the extent of mobilization of cancer cells from the bone marrow to the peripheral blood, the level of cancer cell death and clinical responses.
Eight patients have already been enrolled in the study, out of a total expected enrollment of up to 50 patients at eight clinical sites in the United States and Israel. The study consists of two parts: The current dose escalation phase and a subsequent expansion phase at the highest tolerated dose found during the escalation phase. To date, there reportedly have been no serious adverse events related to BL-8040. The BL-8040 dosing level of the current study cohort is 1 mg/kg, with the highest planned study dose being 1.5 mg/kg.
“We are very excited about the initial results from the Phase 2 trial of BL-8040 in relapsed and refractory AML patients. This is one of our most promising clinical-stage assets, and these results provide further support for the potential of this unique drug,” said Dr. Kinneret Savitsky, CEO of BioLineRx. “We are looking forward to reporting further interim results at the end of the dose escalation phase, expected during the second quarter of 2014, with final study results expected in the second half of 2014. Future development plans for BL-8040 include entering into additional hematological indications, including the commencement of clinical studies in stem cell mobilization and chronic myeloid leukemia during the first half of 2014.”
Dr. Gautam Borthakur, the principal investigator from the MD Anderson Cancer Center in Houston, stated, “AML is a disease with a clear need for new and more effective treatments. Current options are rather limited, and the five-year survival rate is low compared to many other blood cancers. This is particularly true with respect to patients with relapsed or refractory diseases. The initial results of the BL-8040 Phase 2 trial show a remarkable apoptotic effect of the drug on AML cancer cells, and the drug is exceptional in its ability to induce both mobilization of cancer cells from the bone marrow, as well as a concomitant cell death effect. I therefore have high hopes that this drug will become an important addition to the limited drug arsenal for AML treatment.”
BL-8040 is a clinical-stage drug candidate for the treatment of acute myeloid leukemia and other hematological indications. It is a short peptide that functions as a high-affinity antagonist for CXCR4, a chemokine receptor that is directly involved in retention of cancer cells in the bone marrow, tumor progression, angiogenesis, metastasis and cell survival. CXCR4 is over-expressed in more than 70 percent of human cancers and its expression often correlates with disease severity.
“We have strategic relationships with all the leading universities in Israel, as well as substantial connections with many early-stage biotech companies,” Savitsky notes. “Israel is known for its world-leading early-stage research; however, a relatively low number of drugs on the market have historically originated from Israeli technology. BioLineRx was founded in order to bridge this gap.”