Personalised Medicine
Implications for combination development There is another alternative, however. There may be a larger subpopulation of patients in whom more than one mechanism contributes to the man- ifestation of disease. This construct, in fact, is like- ly the most often observed scenario in common, non-monogenic diseases. In many therapeutic areas, including oncology, metabolic diseases, inflammatory diseases, etc, combination therapy is the most common treatment paradigm that patients see. The prevalent use of combinations suggests that healthcare providers intuitively recognise that more than one drug is needed to effectively change clinical manifestations of dis- ease. That is, the correction of more than one mechanism is a necessary part of therapy. In this alternative, instead of seeking solely one dominant path to manipulate (see discussion, vide supra), several molecular pathways may need to be adjust- ed to bring about clinically meaningful treatment outcomes.
The selection of combinations, however, should be data-driven, rather than based on individual agents that appear to have some monotherapeutic
efficacy and are simply combined in anticipation of achieving greater additive efficacy. Similar to the application of anti-viral cocktails in the treatment of HIV, different facets of the pathobiology should be selectively attacked. To do so, the advanced planning and analysis as described above for single targets is critical to enable this effort. Moreover, sponsors would need to focus on the combination as the final product, rather than the individual components. The reason for doing so is that it changes the preparatory work that would be done as well as expectations from any single component. Combinations also have appeal regarding drug
safety. In the current paradigm, single target thera- peutic agents are often designed to inhibit the bio- logical mechanism to the greatest extent possible. If the targeted mechanism plays a critical biological role, then excessive inhibition can create a genetic- like syndrome and yield adverse complications of therapy. In some cases, these complications can force restriction of dosing and a less-than-desired response. By not requiring maximal inhibition of a single target, intelligent combinations have the potential to open new therapeutic possibilities.
KEYNOTES AT DRUG DISCOVERY 2011 Dr Jamie Thomson
University of Wisconsin, Madison
“Current State of Induced Pluripotent Stem cells as compared to Embryonic Stem cells and their role in creating terminal tissue models”
Closing Debate The closing debate has become a signature event at the
Drug Discovery meeting. In 2011 attendees will hear two world-leading, engaging and provocative speakers address the topic of:
‘The future of Drug Discovery: Small Molecules and Biopharmaceuticals’
Advocating for Small Molecules – Chris Lipinski, Melior Discovery Advocating for Biopharmaceuticals – Kevin Johnson, Index Ventures
The Plenary Keynote Presentations are supported by eight scientific sessions across two days.
Register for your FREE place at the best Drug Discovery conference in 2011 at
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54 Drug Discovery World Summer 2011
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