Current Pharmaceutical Pipelines Are Testimony to the Intensity of Breast Cancer...

Tue Jan 8, 2008 1:40pm EST

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Current Pharmaceutical Pipelines Are Testimony to the Intensity of Breast Cancer Drug Development with At Least 50 Investigational Drugs/Drug Combinations in Clinical Development

DUBLIN, Ireland--(Business Wire)--Research and Markets
(http://www.researchandmarkets.com/reports/c78845) has announced the
addition of Drug Targets for Breast Cancer to their offering.

Breast cancer is a complex heterogeneous disease characterised by
uncontrolled growth and spread of abnormal cells. It is also very
prevalent, with reports from the World Health Organization estimating
that more than 1.2 million people will be diagnosed with breast cancer
in 2005, worldwide. In the United States, breast cancer is the second
most common cancer in women (following skin cancer) with 212,930 new
cases estimated for 2004 and an associated 40,840 deaths. In Europe,
approximately 200,000 women are diagnosed with breast cancer each year
(41,000 in the UK). Consequently, breast cancer is a high-priority
research area and is recognized as one of the most aggressively
pursued diseases in the history of medicine.

Encouragingly, cancer drug therapy is in a time of major
transition. This time has been described by Bristol Myers Squibb (New
York, NY), as a "golden era," where decades of cancer research are now
being translated into development of next generation therapeutics.
Current pharmaceutical pipelines are testimony to the intensity of
breast cancer drug development with at least 50 investigational drugs
and drug combinations in clinical development.

This report features:

-- An overview of recent developments in breast cancer research

-- Clearly explains the new approaches to tackling this disease

-- Profiles the new treatments coming to market

-- Takes an in-depth look at the portfolios of the major
developers in this market

This report will allow you to:

-- Understand recent developments in breast cancer research and
how they are set to revolutionise the market

-- Track the development activities of your competitors

-- Identify the potential of new treatments and treatment
approaches for breast cancer

Breast cancer is a complex heterogeneous disease characterized by
uncontrolled growth and spread of abnormal cells. It is also very
prevalent, with reports from the World Health Organization estimating
that more than 1.2 million people will be diagnosed with breast cancer
in 2005, worldwide. In the United States, breast cancer is the second
most common cancer in women (following skin cancer) with 212,930 new
cases estimated for 2004 and an associated 40,840 deaths. In Europe,
approximately 200,000 women are diagnosed with breast cancer each year
(41,000 in the UK). Consequently, breast cancer is a high-priority
research area and is recognized as one of the most aggressively
pursued diseases in the history of medicine.

Breast Cancer Therapeutics

Encouragingly, cancer drug therapy is in a time of major
transition. This time has been described by the pharmaceutical
company, Bristol Myers Squibb (New York, NY), as a "golden era," where
decades of cancer research are now being translated into development
of next generation therapeutics. Current pharmaceutical pipelines are
testimony to the intensity of breast cancer drug development with at
least 50 investigational drugs/drug combinations in clinical
development.

Breast cancer treatment generally comprises of combinations that
include surgery, radiotherapy, hormonal therapy, and chemotherapy.
Clinical pipelines now reflect the emergence of two additional new
therapy classes, namely, "innovative therapy" and "immunotherapy."
Presently, treatment is somewhat dominated by hormone or endocrine
therapy as approximately 70% of breast cancers are hormone-responsive.
In particular, and since the mid-1970s, the antihormonal drug,
tamoxifen (Nolvadex(R); AstraZeneca plc, London, UK), has become
established as a "gold standard" of treatment for hormone-responsive
breast cancers. More recently, new and improved hormonal therapies
have emerged and are expected to ultimately replace tamoxifen.

These primarily include the aromatase inhibitors and to a lesser
extent, "pure estrogens." Three key approved aromatase inhibitors are
Arimidex(R) (anastrazole, AstraZeneca plc, London, UK), Femara(R)
(letrozole, Novartis AG, Basel, Switzerland), and Aromasin(R)
(exemestane, Pfizer Inc, New York, NY). Faslodex(R) (fulvestrant;
AstraZeneca plc London UK) is an approved "pure estrogen." Current
pipeline developments include new aromatase inhibitors and additional
indications for approved therapies. Additionally, three endocrine
therapies (known as SERMs) are in development. These therapies have
estrogen-blocking activity against breast and endometrium tissue while
maintaining estrogen protective activity against the bone and heart,
for example. With an increasing range of endocrine therapies comes an
increasing range of options for the physician and patient.

In addition to hormonal/endocrine therapy, the three other classes
of drug therapies relevant to breast cancer are "innovative therapy,"
"immunotherapy," and chemotherapy. Innovative and immunotherapy
represent a new approach in cancer treatment known as targeted
therapies. These "new generation" therapies are built on a foundation
of at least two decades of breast cancer research--and development of
a major knowledge base on the molecular etiology of breast cancer. The
output of these studies is the identification of new drug targets,
which has accelerated drug development. Drugs associated with
innovative therapies generally target key

signaling molecules/pathways associated with cancer development.
These include drugs that target growth factor receptors (e.g. the EGF
or IGF receptor), angiogenesis, farnesylation, the MEK pathway, the
mTOR pathway, apoptosis, DNA synthesis and repair, and the proteasome.
Some small molecules in development target more than one pathway such
as lapatinib (GlaxoSmithKline plc, Brentford, Middlesex, UK), a dual
tyrosine kinase inhibitor that targets EGFR and HER2. This capacity
considerably expands the therapeutic potential of this drug with
potential for overcoming drug resistance that may develop against one
pathway.

The "immunotherapy" class comprises largely of therapeutic
vaccines and monoclonal antibodies. Immunotherapy acts to harness the
potential of patients own immune system (or boost its potential) to
fight cancer. No therapeutic vaccines have yet been approved for
breast cancer but several are in advanced development. PANVAC(TM)-VF
(and docetaxel) is in Phase II of development at Therion Biologics
(Cambridge, MA). This vaccine is based on the principle of educating
the immune system to recognize cancer-specific antigens and cause an
immune response. At Dendreon Corp. (Seattle, WA), a breast cancer
vaccine is in Phase I of development that targets HER2 positive
cancers. In parallel to vaccine development is adjuvant development.
With propensity to enhance the immune response, relevant adjuvants are
in development at Galencia Pharmaceuticals (Birmingham, AL) and Corixa
Corp. (Seattle, WA). Another major component of immunotherapy is
monoclonal antibody development. The first approved monoclonal
antibody for breast cancer is Herceptin(R) (trastuzumab; Genentech,
Inc, South San Francisco, CA). This has been a major success and is
used to treat patients with HER2/neu positive phenotypes.
Herceptin(R), FDA approved in 1998 is now under investigation as a
treatment for early-stage HER2-positive cancer. HER2 diagnostic
testing has been a significant parallel development to Herceptin(R)
approval and has paved the way for tailoring of therapies to a
specific patient, indicative of a new trend towards personalized
medicine or pharmacogenomics.

Chemotherapy, which generally interferes with the process of cell
division of cancer cells, is a treatment approach utilized over many
decades. Although efficacious, new generation therapies hold promise
for much reduced side effects. New technologies such as liposomal
packaging allow more drug to be delivered more efficiently to the
target site. One example of this is Doxil(R) (doxirubicin; J&J
Pharmaceutical R&D (Raritan, NJ). Another approach is reducing the
usage of solvents (and some of the associated side effects) used with
chemotherapy drugs. Abraxane(TM)

(Abraxis Oncology, CA), is a new mode of chemotherapy where drugs
are packaged via binding to albumin. This solvent-free combination
reduces problems such as hypersensitivity and allows more optimal
dosing. Another advance among chemotherapy agents is the increase in
combinations therapies; a factor that expands their therapeutic
potential. In support of the trend towards less harsh chemotherapy,
AstraZeneca has recently doubled its R&D capabilities in the pursuit
of kinder, gentler, more effective cancer medicines.

Breast Cancer Technologies

Underlying development of breast cancer therapeutics is a diverse
array of enabling technologies. These include technologies associated
with gene cloning and characterization, gene expression profiling,
proteomics, RNAi, bioinformatics, population genetics, and biomarkers.
Central to many of these technologies is their ability to probe the
molecular basis of disease. One output of the study of the molecular
basis of breast cancer is the identification of new biomarkers.

These can provide "early warnings" of cancer from simple serum
tests, as available from Tripath Imaging, Inc (Burlington, NC), for
example. At Veridex LLC (Warren, NJ), circulating tumor cells are a
focus for metastasis detection and prognostic information. Molecular
markers or biomarkers also provide a basis for diagnostic tests, which
allows for more accurate prognosis. The FDA approved two diagnostic
tests for HER2 testing as a prelude to Herceptin(R) therapy. These are
the Ventana Inform test (Ventana Medical Systems) and the Pathyvision
test (Abbott-Vysis partnership). Prediction of cancer metastasis is an
area of investigation through gene expression profiling of breast
cancer samples. This facilitates identification of "gene signatures"
relating to breast cancer and is an approach utilized at Agendia BV
(Amsterdam, The Netherlands) and Ipsogen (Marseille, France).
Clinically relevant insights of breast cancer gene expression are also
emerging by application of proteomics to bio-fluids and biopsy
specimens. Integrating the knowledge banks accumulating in breast
cancer is taking place through the emerging science of bioinformatics.
IT-based infrastructure is being utilized in initiatives such as the
National Cancer Institute's Bioinformatics Grid, a platform for data
sharing at a national level.

Breast Cancer Markets

Oncology is recognized as the third largest segment of the world's
pharmaceutical markets. The oncology market has estimated global sales
of $40 billion, with growth projected at 10%. Of this segment, the
market associated with breast cancer therapeutics is approximately
$6.2 billion, the largest market in oncology. In the breast cancer
market, clinical pipelines exhibit a wide range of new generation
"innovative" and "immunotherapy" drug candidates. Consequently,
transformation of the oncology marketplace is predicted over the next
decade. Growth in the market is expected to be driven by the ageing
population and increases in the incidence of breast cancer. Sales
revenues of endocrine therapies in 2004 for breast cancer are just
under $2.0 billion. Revenues have been increased significantly by the
approval and uptake of aromatase inhibitors. This increase
counterbalances a drop in revenue from drugs such as Nolvadex(R),
which have come off patent recently. In looking ahead,
GlaxoSmithKline's lapatinib (an innovative therapy) is forecast to
achieve blockbuster sales in 2012 and is a frontrunner of the
innovative class. In chemotherapy, Abraxane (Abraxis Oncology, CA) is
set to become a key cytotoxic.

The Future and Breast Cancer

Breast cancer treatment is set to change significantly. More
targeted therapies with reduced adverse effects are likely to soon
dominate the market place. Therapeutics relating to the innovative
therapies and immunotherapies are likely to be the most novel. The
sector eagerly awaits progress with therapeutic vaccines in
development, in particular. Realization of the therapeutic potential
of these therapies is likely to make a large impact as concepts such
as "immune surveillance" for micro-metastasis are tested. Approval of
combination therapies is likely to expand therapeutic and market
potential of existing therapies. Similarly, single agents that target
multiple pathways are also likely have increased therapeutic and
market potential. Gentler, more technologically advanced chemotherapy
treatments are emerging. Given these developments, the challenge now
is to intensify research so that the intricacies of molecular
signaling pathways might be further elucidated and more drug targets
identified. These new approaches to cancer treatment, along with
healthy clinical pipelines provide hope for halting breast cancer
progression, amelioration of symptoms, and improvement in a patient's
quality of life.

Companies Mentioned:

-- Aeterna Zentaris Inc

-- Agendia BV

-- American Pharmaceutical Partners, Inc

-- Array BioPharma Inc

-- AstraZeneca plc

-- Bristol Myers Squibb

-- Dendreon Corporation

-- Eli Lilly and Company

-- Genentech, Inc

-- Genta, Inc.

-- Igeneon