- Data strongly suggest BL-8040 has potent anti-leukemic activity
in combination with Ara-C in AML -
- Results to be presented at 2015 ASH Annual Meeting -
BioLineRx Ltd. (NASDAQ, TASE: BLRX), a clinical-stage biopharmaceutical
company dedicated to identifying, in-licensing and developing promising
therapeutic candidates, announced today positive results from the dose
escalation part of BL-8040’s Phase 2 clinical trial in relapsed or
refractory acute myeloid leukemia (r/r AML). The results will be
presented at the 57th
American Society of Hematology (ASH) Annual Meeting, to be held
December 5-8, 2015 in Orlando, Florida.
Results showed that BL-8040, as a single agent and in combination with
Cytarabine (Ara-C), was safe and well tolerated at all doses tested up
to and including the highest dose level of 1.5 mg/kg, with no major
adverse events. The composite complete remission rate, including both
complete remission (CR) and complete remission with incomplete blood
count recovery (CRi), was 38% in subjects receiving only one cycle of
BL-8040 treatment at doses of 1 mg/kg and higher (n=16). Patients
included in this part of the study were patients that had undergone a
significant number of prior treatment cycles or that were refractory to
induction treatment.
Treatment with BL-8040 had a triple effect on the leukemic cells. First,
following only two days of monotherapy, BL-8040 triggered an average
40-fold mobilization of immature AML progenitor cells from the bone
marrow to the peripheral blood, thereby sensitizing these cells to the
Ara-C chemotherapy and improving its efficacy. Second, BL-8040 showed a
direct and significant apoptotic effect on the immature leukemia
progenitor cells in the bone marrow following the two days of
monotherapy. Last, BL-8040 induced leukemia progenitor cells towards
differentiation, as evidenced by a 58% median decrease in the number of
bone marrow leukemia progenitor cells, along with a three-fold increase
in differentiated granulocytes, in the bone marrow biopsy conducted on
Day 3 of the treatment cycle prior to the Ara-C treatment, as compared
to the biopsy performed at baseline.
Dr. Jorge Cortes, Chief of the AML and CML Sections at the MD Anderson
Cancer Center in Houston, stated, “The clinical results from the dose
escalation stage of the Phase 2 study for BL-8040 in r/r AML are very
encouraging and fully support continued development of the compound in
the AML space.”
Dr. Kinneret Savitsky, CEO of BioLineRx, commented, “We are very pleased
and encouraged by the positive results from the first part of this Phase
2 trial with BL-8040 for the treatment of r/r AML, especially in light
of the severity of the patient population recruited and the short
treatment regimen of one cycle. The results continue to demonstrate that
BL-8040 not only significantly induces mobilization of leukemic cells
from the protective microenvironment of the bone marrow into the
peripheral blood, but also directly leads to apoptosis of leukemic
progenitor cells and triggers terminal differentiation of the cells into
granulocytes. Combined with the reported 38% remission rate from
subjects receiving BL-8040 doses of at least 1 mg/kg, the results
strongly suggest that BL-8040 has potent anti-leukemic activity and, in
combination with Ara-C, may improve the response typically achieved in
this advanced AML population.” Dr. Savitsky continued, “In light of the
encouraging results, we look forward to discussions with the regulatory
authorities regarding the future development plan for AML. We currently
anticipate reporting topline results from the full study by early next
year.”
“In order to further expand and enhance the potential of this unique
oncology platform, we are continuing to perform and plan multiple
additional clinical studies for BL-8040. These include a Phase 2b study
which we recently initiated for BL-8040 as an AML consolidation
treatment; a Phase 2 study in the planning stages as a novel stem cell
mobilization treatment, based on input that we received from the FDA
last month; and two additional studies in certain bone marrow failure
indications and for the treatment of AML patients with the FLT3-ITD
mutation,” concluded Dr. Savitsky.
About the r/r AML Phase 2 study
The Phase 2 trial is a multicenter, open-label study under an IND,
conducted at ten clinical sites in the U.S. and Israel, and is designed
to assess the safety, efficacy pharmacodynamics and pharmacokinetic
parameters of BL-8040 in combination with Cytarabine (Ara-C) for the
treatment of adult relapsed or refractory AML patients. Twenty-two
patients with r/r AML were enrolled in the dose escalation stage of the
study (16 of which received a dose of 1 mg/kg and higher), which
includes a dose escalation stage followed by an expansion stage. In the
dose escalation stage, each patient received a once daily dose of
BL-8040 monotherapy (from 0.5 to 1.5 mg/kg) on days 1-2 followed by the
same dose of BL-8040 plus Ara-C on days 3-7. Extensive pharmacodynamic
parameters, such as mobilization of leukemic cells and induction of
apoptosis, were assessed after monotherapy with BL-8040 using peripheral
blood sampling and bone marrow aspirates at baseline and on Day 3 prior
to Ara-C administration. Clinical response to treatment was evaluated by
bone marrow biopsy on Day 30.
About BL-8040
BL-8040 is a clinical-stage drug candidate for the treatment of acute
myeloid leukemia, as well as 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 tumor progression,
angiogenesis (growth of new blood vessels in the tumor), metastasis
(spread of the disease to other organs or organ parts) and cell
survival. CXCR4 is over-expressed in more than 70% of human cancers and
its expression often correlates with disease severity. In a Phase 1/2,
open-label, dose escalation, safety and efficacy clinical trial in 18
multiple myeloma patients, BL-8040, when combined with G-CSF,
demonstrated an excellent safety profile at all doses tested and was
highly effective in the mobilization of hematopoietic stem cells and
white blood cells from the bone marrow to the peripheral blood.
Additionally, in a Phase 1 stem-cell mobilization study in healthy
volunteers, BL-8040 as a single agent was safe and well tolerated at all
doses tested and resulted in efficient stem-cell mobilization and
collection in all study participants. Importantly, the results of this
study support the use of BL-8040 as one-day, single-dose collection
regimen, which is a significant improvement upon the current standard of
care.
BL-8040 also mobilizes cancer cells from the bone marrow and may
therefore sensitize these cells to chemo- and bio-based anti-cancer
therapy. Importantly, BL-8040 has also demonstrated a direct anti-cancer
effect by inducing apoptosis. Pre-clinical studies show that BL-8040
inhibits the growth of various tumor types including multiple myeloma,
non-Hodgkin’s lymphoma, leukemia, non-small cell lung carcinoma,
neuroblastoma and melanoma. BL-8040 also significantly and
preferentially stimulated apoptotic cell death of malignant cells
(multiple myeloma, non-Hodgkin’s lymphoma and leukemia). Significant
synergistic and/or additive tumor cell killing activity has been
observed in-vitro and in-vivo when tumor cells were treated with BL-8040
together with Rituximab, Bortezomib, Imatinib, Cytarabine and the FLT-3
inhibitor AC-220 (in NHL, MM, CML, AML, and AML-FLT3-ITD models,
respectively). In addition, the current Phase 2 clinical trial in AML
patients has demonstrated robust mobilization and apoptosis of cancer
cells. BL-8040 was licensed by BioLineRx from Biokine Therapeutics and
was previously developed under the name BKT-140.
About Acute Myeloid Leukemia (AML)
Acute myeloid leukemia (AML) is a cancer of the blood and bone marrow
and is the most common type of acute leukemia in adults. According to
the American Cancer Society, approximately 19,000 new cases of AML were
diagnosed in the United States in 2014, and the median age of AML
patients was 67 years old. The first treatment line for patients with
AML includes a combination of chemotherapy drugs and is called induction
treatment. The median survival for AML patients receiving induction
chemotherapy is less than two years, with shorter survival for patients
over the age of 60 or for those with certain gene or chromosome
aberrations. Due to relapsed or refractory disease (where the disease is
not responsive to standard treatments), the overall five-year survival
rate for AML is between 10 and 40 percent.
About BioLineRx
BioLineRx is a publicly-traded, clinical-stage biopharmaceutical company
dedicated to identifying, in-licensing and developing promising
therapeutic candidates. The Company in-licenses novel compounds
primarily from academic institutions and biotech companies based in
Israel, develops them through pre-clinical and/or clinical stages, and
then partners with pharmaceutical companies for advanced clinical
development and/or commercialization.
BioLineRx’s current portfolio consists of a variety of clinical and
pre-clinical projects, including: BL-8040, a cancer therapy platform,
which is in the midst of a Phase 2 study for relapsed/refractory acute
myeloid leukemia (AML), has recently initiated a Phase 2b study as an
AML consolidation treatment, and has successfully completed a Phase 1
study in stem cell mobilization; and BL-7010 for celiac disease, which
has successfully completed a Phase 1/2 study.
In December 2014, BioLineRx entered into a strategic collaboration
with Novartis for the co-development of selected Israeli-sourced novel
drug candidates. The companies intend to co-develop a number of
pre-clinical and early clinical therapeutic projects through clinical
proof-of-concept for potential future licensing by Novartis.
For more information on BioLineRx, please visit www.biolinerx.com
or download the investor relations mobile device app, which allows users
access to the Company’s SEC documents, press releases, and events.
BioLineRx’s IR app is available on the iTunes App Store as well as the
Google Play Store.
Various statements in this release concerning BioLineRx’s future
expectations, including specifically those related to the development
and commercialization of BL-8040, constitute “forward-looking
statements” within the meaning of the Private Securities Litigation
Reform Act of 1995. These statements include words such as “may,”
“expects,” “anticipates,” “believes,” and “intends,” and describe
opinions about future events. These forward-looking statements involve
known and unknown risks and uncertainties that may cause the actual
results, performance or achievements of BioLineRx to be materially
different from any future results, performance or achievements expressed
or implied by such forward-looking statements. Some of these risks are:
changes in relationships with collaborators; the impact of competitive
products and technological changes; risks relating to the development of
new products; and the ability to implement technological improvements.
These and other factors are more fully discussed in the “Risk Factors”
section of BioLineRx’s most recent annual report on Form 20-F filed with
the Securities and Exchange Commission on March 23, 2015. In addition,
any forward-looking statements represent BioLineRx’s views only as of
the date of this release and should not be relied upon as representing
its views as of any subsequent date. BioLineRx does not assume any
obligation to update any forward-looking statements unless required by
law.
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