This page contains a Flash digital edition of a book.
Personalised Medicine


Addressing stakeholder concerns It is expectable that stakeholder groups may have concerns about the recommended approach of subselecting patient populations. Scientists may be concerned about putting all of their efforts into a programme that hinges on the correct, early identification of the response group. What if the analysis is wrong? How would the complexity of a combination need to be managed? Commercial colleagues might be concerned that the market size and total reim- bursement could be too small to underwrite the costs of discovering, developing and marketing this agent.


These are legitimate concerns that can be addressed. There is a risk if only a specific sub- type were to be studied in a Phase IIa POC study. If that result were negative, then it would not be clear whether the general group of patients would have responded differently. To address that concern, a sponsor could stratify its Phase II study by including the subselected as well as the more general patients in a balanced design. That way, a comparison between the selected subpop- ulation and the entire population could be pro- vided to the sponsor. A data-driven choice could then be made by the team, including additional molecular analyses on both populations. This is similar to the study design for trastazumab effi- cacy in HER-2 positive and negative subjects. Commercial colleagues can use these data to project market capture of subgroup efficacy ver- sus the entire disease population.


Conclusions


The essence of personalised healthcare, ie identify- ing and treating the key, causal factors in a patient’s disease, is a popular topic that has been well discussed by others24,38. This paper specifi- cally focuses on the need for personalised drug dis- covery and development from the beginning of the process. The pharmaceutical industry’s Phase II future successes will likely depend upon effectively enacting this paradigm. To successfully execute a personalised healthcare approach to drug discov- ery and development, including the possibility of combinations, it is critical to categorise patient subtypes in advance (Figure 4). By doing so, bio- logical targets can be carefully chosen and appro- priate mechanistic biomarkers identified in advance of the investigational compound entering the clinic. Modern analytical tools exist that make molecular subsegmentation of disease now possi- ble. It is critical to recognise that advance planning is necessary to enable this approach. Without it,


Drug Discovery World Summer 2011


sponsors will most often be reactive to Phase II data and likely be saddled with the same Phase II success rates.


Acknowledgements


The authors thank Daphna Laifenfeld, PhD for her critical review of the manuscript.


DDW


Dr David A Fryburg is the Chief Medical Officer at Selventa. With more than 20 years of clinical and pharmaceutical research experience, Dr Fryburg is an expert in developing translational medicine strategies for effective drug discovery and development. Prior to joining Selventa, he was at Pfizer and served on the faculty of the University of Virginia Health Sciences Center.


Dr Diane H Song is the Marketing and Scientific Development Manager at Selventa. Dr Song has more than 15 years of oncology and metabolic disorders- related research experience. Prior to joining Selventa, she was a faculty member at Boston Medical Center, where her research was recognised through numerous grant awards and speaking opportunities.


Dr David de Graaf is the President and Chief Executive Officer of Selventa. Dr de Graaf, who has more than 20 years of scientific and opera- tional industry experience, is an expert in systems biology and its application to personalised health- care. Prior to joining Selventa, he was at Boehringer-Ingelheim, Pfizer, AstraZeneca and the Whitehead/MIT Center for Genome Research.


55


Figure 4


Contrasting the current paradigm for drug development and the new paradigm of personalised drug discovery and development. In current practise (panel A), despite recognition that a disease can have one or more mechanistic drivers, drugs are developed to manipulate the clinical aspect of disease. For inclusion in the clinical trial, subjects are generally not selected by mechanism. In a personalised approach, patients are matched to the


mechanisms causing the clinical manifestation of their disease (panel B). This new paradigm has significant implications for the definition of disease, market sizes, and success rates


Page 1  |  Page 2  |  Page 3  |  Page 4  |  Page 5  |  Page 6  |  Page 7  |  Page 8  |  Page 9  |  Page 10  |  Page 11  |  Page 12  |  Page 13  |  Page 14  |  Page 15  |  Page 16  |  Page 17  |  Page 18  |  Page 19  |  Page 20  |  Page 21  |  Page 22  |  Page 23  |  Page 24  |  Page 25  |  Page 26  |  Page 27  |  Page 28  |  Page 29  |  Page 30  |  Page 31  |  Page 32  |  Page 33  |  Page 34  |  Page 35  |  Page 36  |  Page 37  |  Page 38  |  Page 39  |  Page 40  |  Page 41  |  Page 42  |  Page 43  |  Page 44  |  Page 45  |  Page 46  |  Page 47  |  Page 48  |  Page 49  |  Page 50  |  Page 51  |  Page 52  |  Page 53  |  Page 54  |  Page 55  |  Page 56  |  Page 57  |  Page 58  |  Page 59  |  Page 60  |  Page 61  |  Page 62  |  Page 63  |  Page 64  |  Page 65  |  Page 66  |  Page 67  |  Page 68  |  Page 69  |  Page 70  |  Page 71  |  Page 72  |  Page 73  |  Page 74  |  Page 75  |  Page 76  |  Page 77  |  Page 78  |  Page 79  |  Page 80  |  Page 81  |  Page 82  |  Page 83  |  Page 84  |  Page 85  |  Page 86  |  Page 87  |  Page 88  |  Page 89  |  Page 90  |  Page 91  |  Page 92