To be presented today at the 34th CTRC-AACR San Antonio Breast Cancer
Symposium (SABCS) in Texas, USA, the status of the clinical trial to
evaluate Reparixin safety and pharmacokinetic profile,
administered orally in combination with paclitaxel in women with
metastatic breast cancer.
The second cohort has been completed in patients where limiting
toxicity has not been observed, supporting the safety profile for
the candidate drug. The evaluation of the third cohort is being carried
out and will be completed in the first quarter 2013. A further 9
patients are expected to be enrolled at 3 prominent Oncological
Centers in the US.
Dr Anne Schott is the Coordinator and Investigator of the study
as well as the author of the presentation. Dr Schott is Associate
Professor in the Department of Internal Medicine at the University of
Michigan Comprehensive Cancer Center. The discovery of the potential
of Reparixin in the treatment of Cancer Stem Cells (CSCs) was
contributed by the director of the UMCC, Prof Max Wicha.
"Reparixin is a promising molecule, with a good safety profile, as
the positive conclusion of the second study cohort on women with metastatic
cancer has shown - states Dr Anne Schott - Such
results motivate us to continue the characterization of this molecule
which could represent an innovative therapy for metastatic breast
cancer, presently still hard to cure."
Based on the excellent safety profile demonstrated, it has been
announced today, at SABCS, the setting up of a new, important,
clinical study aimed at evaluating the effects of Reparixin in oral
monotherapy on CSCs and on tumor microenvironment for the treatment of
women with early stage breast cancer, before surgery.
The study will involve a total of 7 Clinical Centers in the US
coordinated by Dr Lori Goldstein, Director of the Breast
Evaluation Center and leader of the Breast Cancer Research Program
at of the Department of Medical Oncology at the Fox Chase Cancer
Center of Philadelphia (US).
The first center that has been activated is the Methodist Hospital
Research Institute of Houston, Texas, which is expected to enroll
the first patient in December.
"I have always believed that a therapy aimed at cancer stem cells
could represent the future of research in the field of breast cancer
and, more in general, in the fight against cancer. For such reasons, I
have strongly supported the clinical development of Reparixin - asserts
Dr Jenny Chang, Principal investigator and Director of the
Methodist Hospital Research Institute of Houston - What we want to
demonstrate with the new study is that Reparixin can represent a future
opportunity for the treatment of both metastatic disease and early
Reparixin is an inhibitor of the CXCR1 receptor activated by chemokine
interleukin 8. The molecule, discovered and characterized in Dompé's
research laboratories - a biopharmaceutical company - has demonstrated
to be able to selectively attack cancer stem cells of breast cancer.
Therapies aimed at CSCs represent a great promise for the cue of cancer
but the uniqueness of the mechanism requires innovative approaches and
the development of specific biomarkers able to address the selection of
the patient and to follow the drug action. Obtaining a proof of concept
in planned studies can have important implications even in therapies of
other tumoral forms still lacking therapies.
In fact, the particular action mechanism of Reparixin, which modifies
the microenvironment in which cancer stem cells are produced and
developed, could be applied not only for breast cancer but also as a
therapy for other tumors.
"Reparixin is one of the molecules fruit of our commitment in
R&D and the results achieved so far, stimulate us to face a complex and
innovative development program in the field of oncology, an area still
characterized by a high therapeutical need - states Dr Eugenio
Aringhieri, Chief Executive Officer of Dompé Group - We are proud
to be able to contribute to the fight against this disease which affects
millions of Patients globally, as well as establishing the fame of
Italian research at the international level, by counting on the most
important US centers of excellence, committed to preside
over a hot area of research such as that of cancer stem cells."
Reparixin is an inhibitor of the CXCR1 receptor which in the body is
activated by chemokine interleukin-8 that plays a key role in
It is the first in a novel class of low-molecular weight inhibitors that
can selectively modulate the receptor activity via an allosteric
mechanism of action. An allosteric inhibitor can freeze the receptor in
an inactive position binding it to a different site than the site taken
by the natural ligand (IL-8). Made in collaboration with the research
team led by Prof. Alberto Mantovani, world leading expert in chemokine
research, the characterization of the action mechanism of Reparixin is a
mainstay in the research of drugs capable of modulating the activity of
this important receptor family.
About REP0111 - Study on Reparixin in HER-2 negative metastatic
Phase 1b of the study gave the "go ahead" to REP0210, Reparixin has
demonstrated in preclinical studies, to be efficacious both as a
monotherapy as well as combined with (synergic effect) classical
chemotherapies used for breast cancer (docetaxel in particular) to
reduce cancer stem cells.
The primary objective of the study is the evaluation, in women over 18
with HER-2 metastatic breast cancer, of the pharmacokinetic and safety
profile for the combined treatment with Reparixin on CSCs, on the
tumoral microenvironment and on plasmatic levels of inflammatory
cytokines, and the analysis of the tumor response to the treatment as an
indicator of efficacy.
Patients receive a cycle of 3 days of treatment with Reparixin oral
tablets 3 times a day followed by a cycle of combined treatment with
paclitaxel 80mg/m2/week + oral Reparixin 3 times per day for 21 days, in
three different dosages (400 mg, 800 mg, 1200 mg). Safety is evaluated
after the first cycle, and the treatment will continue until the
observation of clinical benefits.
Currently, the second cohort of 3 patients where no toxicity has been
observed has been completed to confirm the safety profile of the
candidate drug. The third cohort is currently enrolling and will be
concluded in the first trimester 2013. Another 10 patients are expected
to be enrolled at three clinical sites in the US.
About REP0111 - Study on Reparixin in early HER-2 negative metastatic
REP0210 is a pilot clinical study in 40 patients with operable breast
cancer, subdivided in 2 different subgroups based on the receptor
characteristics of the tumor, and treated in monotherapy with Reparixin
orally before surgical treatment. The study aims at evaluating, in the
two subgroups, the effects of Reparixin on cancer stem cells (CSCs) in
early stage tumors and in the tumoral microenvironment, namely to verify
whether Reparixin is effectively able to reduce CSCs and related
markers, and to evaluate possible differences between the two subgroups
with the aim to precisely identify the "ideal" target population for
this innovative treatment. The two subgroups of patients will be
Estrogen Receptor positive (ER+) and/or Progesterone Receptor positive
(PR+)/HER2- respectively, and ER- and/or PR-/HER2-.
CSCs will be measured through cytofluorimetry in samples of bioptic
tissue, which will be subjected to PCR-RT and/or immunohistochemistry
and to the dosage of: epithelial-mesenchymal markers, of the
serine/threonine protein-kinase AKT, of the focal-adhesion-kinase(FAK)
and of receptor CXR1 levels. Analogously, the study will also measure
antinflammatory and angiogenesis marker levels, infiltrating leucocytes
and markers of autophagy (P62 and LC3).
A leading pharmaceutical company in Italy Dompé develops innovative
treatment solutions for diseases that have a high social impact, which
are often orphan diseases. Based in Italy with HQ in Milan Dompé focuses
on Research in areas where there are still unmet treatment needs such as
juvenile diabetes, ophthalmology and oncology. Its industrial site in
L'Aquila (Abruzzi) has biotechnology facilities for the production of
monoclonal antibodies and the development of Primary Care drugs that are
sold internationally in over 60 countries. In 2012, Dompé acquired
Anabasis, an Italian biotech company that develops innovative drugs
based on rhNGF (whose discovery earned Professor Rita Levi Montalcini
the Nobel Prize for Medicine) for serious eye diseases for which there
are no effective treatments available.
For more information: www.dompe.com
This press release refers to some information that may not correspond
to future results. Dompé firmly believes in the soundness and
reasonableness of the concepts expressed, but some of the information is
subject to a margin of uncertainty, regarding research and development
and appropriate inspections by the relevant regulatory bodies.
Therefore, for the moment, Dompé cannot guarantee the consistency of
expected results in relation to the above.
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