AB Science Reports Positive Clinical Study
Data
Follow-up of Phase 2 of Masitinib in Second-Line
Metastatic Colorectal Cancer confirms Efficacy in Multiple Survival
Endpoints
AB Science SA (NYSE Euronext - FR0010557264 - AB),
a pharmaceutical company specializing in the research, development
and commercialization of protein kinase inhibitors (PKIs), today
announced encouraging follow-up results from a phase 2 study with
its investigational drug, masitinib, in patients with
nonresectable, metastatic colorectal cancer after progression to
first-line treatment.
This was a prospective, multicenter, open label
phase 2 study testing masitinib in combination with three
standard-of-care chemotherapies including FOLFIRI, FOLFOX, and
gemcitabine. Primary endpoint was overall survival (OS) and
secondary endpoints included progression-free survival (PFS) and
overall response rate (ORR). AB Science has previously reported a
survival benefit for masitinib plus FOLFIRI (irinotecan,
5-fluorouracil and folinic acid) in this indication based on
preliminary data analysis with a median OS of 14.5 months [press
release dated 02 December 2013]. One year later, after a median
follow-up of approximately 23 months, this survival benefit has
been confirmed with a median OS of 18.0 months. Of note,
approximately 50% of the masitinib plus FOLFIRI treatment cohort
were positive for the KRAS mutation. These results compare
favorably to published results for second-line FOLFIRI treatment in
which median OS was reported as 12.5 months in patients with
wild-type KRAS and 11.1 months in patients with mutant KRAS
[Peeters et al. (2010) J Clin Oncol 28: 4706-4713].
The survival endpoints of PFS and ORR were also
favorable for masitinib plus FOLFIRI when compared with historic
benchmarks, regardless of KRAS mutation status. In the overall
study population, median PFS was 6.2 months as compared with 3.9 to
4.9 months for the FOLFIRI benchmark, and ORR was 28% as compared
with 10% to 14% for the FOLFIRI benchmark [Peeters et al. (2010) J
Clin Oncol 28: 4706-4713]. Of significance, one patient reported a
confirmed complete response, which is an exceptional observation in
this clinical setting. Safety data showed that the combination of
masitinib and FOLFIRI has an acceptable safety profile. Full data
has been submitted for publication to the American Society of
Clinical Oncology (ASCO) 2015 Annual Meeting.
The decision to move to the currently recruiting
phase 3 study was based on encouraging preliminary results from
phase 2, a decision that is corroborated by these follow-up
data.
Professor Christophe Borg (University Hospital,
Besançon, France), and a leading investigator on this study
declared: "Results from this phase 2 study are impressive. Of
particular interest is the comparatively high overall response
rate. In comparison the current effect of FOLFIRI alone or in
combination with bevacizumab is very limited regarding response
rate. These data, although preliminary in nature, suggest that
masitinib may potentially offer patients a new active compound for
this disease. Results from the ongoing comparative phase 3 study
will therefore be of great interest."
Professor Olivier Hermine, President of the
Scientific Committee of AB Science commented: "The survival benefit
seen across OS and PFS is consistent with our understanding of
masitinib's mechanisms of action in colorectal cancer. In vitro
data on colorectal cell lines has shown that masitinib acts as a
chemosensitizer of 5-Fluorouracil and irinotecan, the two main
cytotoxic components of FOLFIRI, which may explain improvement in
PFS. Also, the main cellular target of masitinib is the mast cell
and increased mast cell activity in the tumor microenvironment has
been linked to poor prognosis and a protumoral immune response in
colorectal cancer. Moreover, unlike other tyrosine kinase
inhibitors, masitinib acts also as an immune therapy, the benefit
of which is to extend overall survival by controlling the
aggressiveness, transformation, and dissemination of the tumors.
Together, these mechanisms of action represent a strong biological
rationale for masitinib in this indication."
A significant unmet medical need still exists in
metastatic colorectal cancer. The incidence of metastatic
colorectal cancer is estimated at 370,000(1) patients each year in
the countries who cover the cost of the treatment.
(1) Globocan 2008 - Colorectal Cancer Incidence
and Mortality Worldwide in 2008. "Colorectal cancer is the third
most common cancer in men (663 000 cases, 10.0% of the total) and
the second in women (571 000 cases, 9.4% of the total) worldwide.
Almost 60% of the cases occur in developed regions."
www.snfge.asso.fr: « Les métastases sont observées dans 40 à 60%
des cas » p.2
Characteristics of the ongoing phase 3
study in metastatic colorectal cancer
This is an international, multicenter,
randomized, double blind, placebo-controlled, 2-parallel group,
phase 3 study to evaluate the efficacy and safety of masitinib in
combination with FOLFIRI (irinotecan, 5-fluorouracil and folinic
acid) for second-line treatment of patients with metastatic
colorectal cancer. A total of 550 patients enrolled will be
randomised in two groups:
- Group 1: masitinib at 6 mg/kg/day + FOLFIRI (irinotecan,
5-fluorouracil and folinic acid), until disease progression
- Group 2: matching placebo + FOLFIRI (irinotecan, 5-fluorouracil
and folinic acid), until disease progression
The study will measure overall survival as a
primary efficacy criterion. One of the objectives of this ongoing
phase 3 study in colorectal cancer will be to identify those
subgroups that best respond to masitinib.
Status of masitinib clinical development
in human medicine
Masitinib is currently developed in 13 phase III
indications; 7 in oncology, 3 in inflammatory diseases, and 3 in
neurodegenerative diseases. Additionally, a large phase II clinical
program is ongoing, mainly in oncology. In case of positive
results, phase III studies will be initiated following these phase
II studies. Overall, clinical development has been initiated in
more than 30 countries, without any licensing agreement. Therefore,
AB Science has retained full ownership of masitinib.
About masitinib
Masitinib is a new orally administered tyrosine
kinase inhibitor that targets mast cells and macrophages, important
cells for immunity, through inhibiting a limited number of kinases.
Based on its unique mechanism of action, masitinib can be developed
in a large number of conditions in oncology, in inflammatory
diseases, and in certain diseases of the central nervous system. In
oncology due to its immunotherapy effect, masitinib can have an
effect on survival, alone or in combination with chemotherapy.
Through its activity on mast cells and consequently the inhibition
of the activation of the inflammatory process, masitinib can have
an effect on the symptoms associated with some inflammatory and
central nervous system diseases and the degeneration of these
diseases.
About AB Science
Founded in 2001, AB Science is a pharmaceutical
company specializing in the research, development and
commercialization of protein kinase inhibitors (PKIs), a
class of targeted proteins whose action are key in signaling
pathways within cells. Our programs target only diseases with high
unmet medical needs, often lethal with short term survival or rare
or refractory to previous line of treatment in cancers,
inflammatory diseases, and central nervous system diseases, both in
humans and animal health. AB Science has developed a proprietary
portfolio of molecules and the Company's lead compound, masitinib,
has already been registered for veterinary medicine in Europe and
in the USA. The company is currently pursuing thirteen phase 3
studies in human medicine in first-line and second-line GIST,
metastatic melanoma expressing JM mutation of c-Kit, multiple
myeloma, metastatic colorectal cancer, metastatic prostate cancer,
pancreatic cancer, mastocytosis, severe persistent asthma,
rheumatoid arthritis, Alzheimer's disease, progressive forms of
multiple sclerosis, and Amyotrophic Lateral Sclerosis. The company
is headquartered in Paris, France, and listed on Euronext Paris
(ticker: AB).
Further information is available on AB Science
website: www.ab-science.com.
This document contains prospective information.
No guarantee can be given as for the realization of these
forecasts, which are subject to those risks described in documents
deposited by the Company to the Authority of the financial markets,
including trends of the economic conjuncture, the financial markets
and the markets on which AB Science is present.
AB Science - Financial Communication & Media
Relations investors@ab-science.com
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