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Current Issues
Biochemical Markers as Tools to Increase Efficiency in Drug Development
a report by
Morten A Karsdal and Dagmar Kasper
Nordic Bioscience, Herlev AAD, and IDS Nordic, Herlev
The current cost of bringing a new medicine to market is estimated to Recently, a novel classification of biomarkers was proposed, referred
be as high as US$0.8–1.7 billion.
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Product development programmes are to as the BIPED classification: Burden of disease, Investigative,
often abandoned after extensive investment of time and resources. This Prognostic, Efficacy of Intervention and Diagnostic. This was proposed
high failure rate increases costs. Even the path to market for successful by by the National Institutes of Health (NIH)-founded Osteoarthritis
candidates is long, costly and inefficient, due in large part to the current (OA) Biomarker Network and has further highlighted the need for
reliance on cumbersome assessment methods. During the last decade, understanding and use of biomarkers in pre-clinical and clinical
the number of new drug and biological applications subimitted to the science. Importantly, an emerging class of biochemical markers that
US Food and Drug Administration (FDA) has declined significantly. are more pathology-specific have been identified. The use of novel
techniques in which specific protein degradation fragments are
As the costs and challenges of medical product development continue investigated has proved valuable for slow-progression diseases such as
to surge, innovation may continue to stagnate or decline; as a result, a osteoporosis (OP) and OA. Specific lessons may be learned from these
long list of health needs will remain unmet. This emphasises the absolute approaches that can be implemented in other diseases. In this article
need to improve the predictability and efficiency of drug development, we will describe two successes in the fields of bone and cartilage, and
thereby providing optimal conditions for projects with the highest describe how some biochemical markers may be unique methods of
probability of success. There is a need for novel methodologies, a drug assessment in translational science (from basic research to clinical
development toolkit containing powerful scientific and technical trials) and therefore could be used as efficacy and safety makers.
methods such as in vitro tests, animal predictive models, biomarkers for
safety and efficacy and new clinical evaluation techniques. We ask the question of whether we can implement what is learned
from diseases such as OP and OA in an optimal drug development
In pre-clinical development it is important to have the necessary tools toolkit that may assist in the safety and efficacy evaluations
to predict human response from disease models. Product efficacy and undertaken between animal and clinical studies. OP is particularly
safety methods are needed to build a brige between disease models suited to this process, as during the last decade the field has evolved
and human experience. However, the combination of better animal from having an absence of assessment techniques and drugs to having
models and tissue-specific biomarkers is important to predict the a selection of validated surrogate markers of efficacy and prognosis
clinical outcome of drugs that are intended for use in any given and a range of potential treatment options. We speculate that this
disease. During the later stages of development in clinical trials there new product development toolkit and methods of application may be
is a demand for innovative and efficient trial designs with improved closer than they appear if the lessons learned from the success of
clinical end-points. assessing protease-generated fragments are further harvested and
applied to other diseases.
A range of important statements have recently been put forward
independently. These may be crucial in the development of a new and Bone and Cartilage – The Challenge of Slow Progression
improved drug development toolkit. Although not exhaustive, this list OP and degenerative joint diseases (DJDs) such as OA and rheumatoid
of important events focuses on two major topics: the ‘Critical arthritis (RA) remain major and growing epidemiological problems
Path Initiative’ and the use of biochemical markers in pre-clinical and worldwide. Due to upward trends of longevity in the elderly
clinical science. populations of industrialised countries, the number of patients
The FDA has articulated a Critical Path Initiative
1
that is a vision
Morten A Karsdal is Head of Research and Development
statement to improve the efficiency of product development
at Nordic Bioscience, which develops treatments and
industry-wide and to identify and prioritise the most pressing diagnostic tools for bone and cartilage diseases. He
development problems for new drugs and therapeutic agents. In
has participated in the development and validation of
a range of biomarkers, both biochemical and image
particular, the FDA Critical Path Initiative attempts to draw attention to
analysis, that are currently used in translational research
new scientific research tools that may revolutionise the regulatory and
and drug development for osteoporosis and osteoarthritis.
He has more than 50 peer-reviewed publications and
scientific process for new product approvals. The FDA stipulates that:
has received investigator awards from various associations
“There is a demand to create new tools to get fundamentally better and societies. Dr Karsdal received his Master of Science from the Technical University of
answers about how the safety and effectiveness of new products can
Denmark in 1998 and his PhD from the Southern University of Denmark in 2004.
be demonstrated, in faster time frames, with more certainty and at
E: mk@nordicbioscience.com
lower costs”.
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© TOUCH BRIEFINGS 2008 17
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