Drug Discovery Today � Volume 16, Numbers 19/20 �October 2011 EDITORIAL

editorial

Elizabeth Foot

Stratifiedmedicine: making

it happen

‘Tailoring medicines to patients is a key challenge for the$750 billion global pharmaceutical market.’Rt Hon David Willetts (Minster of State for Universitiesand Science)

The need to ‘tailor’ medicines and apply emerging science to

better define disease, moving away from clinical phenotyping to

molecular classification, is viewed as not only feasible but the only

way forward to both improve healthcare cost efficiency and

improve patient benefit for patients. Chalkidou and Rawlins

(pp. 873–877) start their paper with the above quote, given by

David Willetts at the launch of the UK Stratified Medicines Inno-

vation Platform. The challenges in implementation of this new

approach are many, and need to be addressed with collaborative

848 www.drugdiscoverytoday.com 1359-6446/06/$ - s

input from many parties. This special issue of Drug Discovery Today

pulls together the views of many key players in the delivery of new

medicines to patients, and achieving enhanced clinical outcomes

within increasingly stretched healthcare budgets. The papers pre-

sented in this issue are based upon talks presented at the 2nd

London Genetics Pharmacogenetics Conference, November 2010

and themes that will be discussed at the 3rd Conference 8–9th

November 2011.

Since the earliest times man has sought to explore the world

around and try and unravel its complexities, be that the mysteries

of the galaxies or how the body works. Through the centuries our

science and understanding of medicine has evolved, often being

spurred on by new windows of insight being opened by accom-

panying advances in technology. The publication of the draft

sequence of the human genome back in 2000 was widely heralded

as a major breakthrough that had the power to revolutionise our

understanding and in turn, our ability to treat disease and develop

novel and more effective medicines. Has that hope been realised?

There are many that would say ‘yes’ but as many that would also

say ‘no’. To realise the potential of new science requires the

collaboration between many different groups including, though

not limited to, academia, pharmaceutical and biotechnology com-

panies, regulatory bodies and payors. It is perhaps the mis-align-

ment of these different groups that is in part responsible for the

seemingly slow realisation of the potential the insights from the

genome and other emerging technologies can bring. This is now

changing and the new era of more personalised medicines is

starting to be realised with examples now both in the clinic and

on the market, notably in the cancer field.

Professor Munir Pirmohamed’s (pp. 852–861) review highlights

the path of pharmacogenetics from the very first example of a

pharmacogenetics trait back in 500BC to the present day and

further illustrates that although pharmacogenetics has led the

way in shaping thinking around stratified medicine, it is not alone

and is one of many so-called ‘-omic’ technologies, including

transcriptomics, metabolomics, proteomics and the study of the

secretome, that are now being applied by industry to better under-

stand disease sub-phenotypes and responding patient groups. It is

under this broader umbrella of biomarkers that most discussion is

now held and shaping thinking on how to apply emerging science

can deliver more cost-effective, value-based medicines in the most

ee front matter � 2011 Elsevier Ltd. All rights reserved. doi:10.1016/j.drudis.2011.09.004

Drug Discovery Today � Volume 16, Numbers 19/20 �October 2011 EDITORIAL

Editorial

efficient way. Demonstrating clinical utility is a core need echoed

across all the papers in this special issue, combined with the need

to show it makes a difference over existing approaches before

being incorporated into clinical guidelines. This applies equally

to safety and efficacy responses.

There are many questions that remain to be answered but

undisputed is the need for pharma to improve the efficiency

and success rate of drug development and for healthcare providers

to find ways to harness the clinical value of new medicines to

benefit the patient but in the most cost-effective way that delivers

value for money.

The regulators have been active in the area working with

pharmaceutical and biotechnology companies to help leverage

the more in-depth understanding of drug response offered by new

technologies. Breckenridge and Prasad (pp. 867–872) provide a

perspective from the Medicines and Healthcare Products Regula-

tory Agency on their experiences, the regulatory guidance and

other initiatives aimed at both engaging with and guiding the

industry on how to incorporate these new approaches. Refresh-

ingly as well as reassuringly, regulatory agencies are also seen to be

working collaboratively in this area with discussions between the

US Food and Drug Administration, European Medicines Agency

and the Japanese Pharmaceuticals and Medical Devices Agency on

pharmacogenetics in drug development. Those involved in drug

development should take all opportunities to access the advice

being offered and to start dialogue with regulators as soon as

possible in the development path of a new medicine.

The concern that revenue will be lost by the development of

niche busters has undoubtedly been troubling the pharmaceutical

industry. Blair and Blakemore (pp. 902–905) provide data of the

value that can be gained by taking a more targeted approach with a

focus on drug-diagnostic co-development. A success in this area,

cited by a number of the authors in this Special Issue is the HIV

medication, abacavir, which exemplifies how both economic gain

and improved patient healthcare can both be achieved. In this

case, demonstration of the association between HLA-B*5701 and

risk of abacavir hypersensitivity led to a drug label change, incor-

poration of gene testing into clinical guidelines and widespread

adoption into clinical practice. Importantly, for the patient this

has enabled greater access to this effective medicine together with

a significant decrease in the incidence of this serious adverse event.

Absolutely key for the future of drug development is the ability

to show cost-effectiveness for any new medicine. With escalating

healthcare costs across the world, the focus on cost-effectiveness is

set to stay. The UK government, for example, has recently

announced moves to introduce value-based pricing from 2014.

Although these incentives for both payers and pharma are impor-

tant for the incorporation of pharmacogenetics and other biomar-

kers into clinical medicine, Chalkidou and Rawlins (pp. 873–877)

from the National Institute for Health and Clinical Excellence put

forward that the major obstacle for adoption is the weak evidence

of effectiveness. Generating the required data can only be achieved

by incorporating these approaches early into clinical trials. They

suggest that dialogue around CEA (cost effective analysis) and

pharmacogenetics is a two-way street between the payors and

pharma companies, emphasizing again this need to work together

to demonstrate clinical utility and address the issues of develop-

ment and commercialisation.

The drivers to identify biomarkers and develop targeted med-

icines are strong. However, identifying robust biomarkers and

demonstrating clinical utility are major challenges for incorporat-

ing into drug development. The perspective on how to overcome

these challenges is presented by the various articles by Nohaile,

Flynn, Wu and Jorgensen (pp. 878–883). Once again the need for

collaboration is seen as central to success particularly in harnessing

the expertise from both drug and diagnostic development and the

science coming out of academia. Consideration of these issues

early in drug development, along with building biomarker

hypotheses into the development path, is critical. To guide think-

ing in this area of biomarker discovery and validation, the Eur-

opean Medicines Agency has developed a Biomarker Qualification

process and issued guidance to help industry in the use of bio-

markers within drug development. In July of this year it issued for

comment (deadline 25th November 2011) a draft reflection paper

on the use of pharmacogenomic biomarkers as patient selection

and treatment stratification tools in drug development. Further

reflection papers have also been released for consultation. Every-

one involved in this field should be encouraged to read and

comment on these documents. These include a Reflection Paper

on methodological issues associated with pharmacogenomic bio-

markers in relation to clinical development and patient selection

and a Reflection Paper on co-development of pharmacogenomic

biomarkers and assays in the context of drug development. A third

is due for release 3Q2011, a Reflection Paper on genomics and

personalised medicines (http://www.ema.europa.eu/).

The goal of clinical development has always been to identify

those patients most likely to achieve optimal benefit from a given

drug. The tools are now available to more effectively predict who

these patients are. However realising these opportunities is chal-

lenging, from identification of robust biomarkers early in the

development path, through to the ability to show cost effective-

ness. There are many players with critical roles in realising the

potential of emerging science. By working together it is hoped that

the ultimate goal of more cost-effective medicines meeting patient

unmet need will be achieved.

Elizabeth FootLondon Genetics Limited, United Kingdomemail: efoot@londongenetics.com

www.drugdiscoverytoday.com 849