Emerging Targets in Diseases with
High Unmet Need: Alzheimer’s
Disease, Lung Cancer, Dyslipidemia, Type 2 Diabetes, and COPD is
a survey of emerging targets in these important diseases. The
report assesses the issues in target-based drug discovery and development
as well as several specific issues that are common to these and
other complex diseases with high unmet medical need.
analysis includes the following:
• Background discussion of the nature of each disease.
• Mechanistic characterization of each disease, and major issues
in diagnosis, stratification, and treatment of each disease.
• Evaluation of leading emerging targets in terms of signaling
pathways and therapeutic strategies.
Currently there are no mechanism-based drugs on the market for
Alzheimer’s disease and COPD, and only one mechanism-based
therapeutic approach is available for lung cancer. While mechanism-based
therapy is available for type 2 diabetes and dyslipidemia, huge
gaps in the therapeutic armamentarium result in inadequate treatment.
Potentially, all of the diseases discussed in this report could
be treated with combination therapies (and, in some cases, possibly
by multitargeted agents) of mechanism-based drugs, if such drugs
Indication-specific highlights presented in this report include
The activities of several companies developing inhibitors of signaling
kinases of the Raf family, which includes B-Raf, are discussed
and evaluated. One such inhibitor, sorafenib (Onyx/Bayer’s
Nexavar) has recently been approved by the Food and Drug Administration
(FDA) for renal cell carcinoma, and is also being developed for
lung cancer. Companies are also developing inhibitors of MEK
(mitogen-activated protein [MAP] kinase kinase) and of Ras
The report chronicles efforts to identify and validate biomarkers
of Alzheimer’s, as well as recent efforts to develop agents
for in vivo imaging of amyloid plaque in animal models and in
human subjects. Emerging drugs, such as Targacept’s selective
small-molecule compounds that target the neural nicotinic receptors
(NNRs), are also evaluated.
An examination of the benefits and limitations of statins is presented,
as well as new approaches to prevention and treatment of cardiovascular
disease. Important activities in this area include efforts to
target CETP. There are now three drug candidates in Phase II
or Phase III clinical trials, including Pfizer’s torcetrapib,
a small-molecule CETP inhibitor delivered in a fixed combination
with the company’s atorvastatin.
Perhaps the greatest problem in discovering new drugs for type
2 diabetes is the lack of scientific understanding of the disease,
and of metabolic syndrome, which usually precedes it. The report
discusses the efforts of companies such as Metabolex, a biotechnology
company whose mission is to discover and develop new diabetes
drugs based on increased scientific understanding.
Many classes of drugs being developed for other inflammatory conditions
might be applicable to COPD. However, in many cases, systemic
and chronic administration of broad-spectrum anti-inflammatory
drugs (such as those that target signal transduction pathways
involved in inflammation) would have unacceptable side effects.
Of drugs under development for COPD, PDE4 inhibitors (specifically,
cilomast and roflumilast) may reach the market in 2006 or 2007,
provided that they can overcome concern with potential side effects
at regulatory agencies. If approved, they will be the first mechanism-specific
drugs with the potential to affect the course of COPD.
About the Author
Allan B. Haberman, Ph.D., is Principal
of Haberman Assoc iates (http://www.biopharmconsortium.com),
a consulting firm specializing in science and technology strategy
for pharmaceutical, biotechnology, and other life science companies.
He is also a Principal and Founder of the Biopharmaceutical Consortium,
an expert team formed to assist life science companies, research
groups, and emerging enterprises to identify and exploit promising,
breakthrough technologies. Dr. Haberman’s consulting activities
include work in new product development and technology strategy,
opportunity assessment, assessment of drug pipelines, and due
diligence on established and emerging biotechnology companies.
He is also the author of numerous publications on the pharmaceutical
and biotechnology industries, their technologies and products,
and on the major therapeutic areas for drug discovery and development.
Prior to forming Haberman Associates, Dr. Haberman was the Associate
Director of the Biotechnology Engineering Center at Tufts University.
He received his Ph.D. in biochemistry and mo lecular biology
from Harvard University.