Abstract
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.
Comprehensive 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 were
developed.
Indication-specific highlights presented in this report include the following:
Lung Cancer
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
Alzheimers
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.
Dyslipidemia
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.
Diabetes
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.
COPD
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.
| 
View Cart
