An analysis of the attrition of drug candidates from four major pharmaceutical companies

ANALYSIS

An analysis of the attrition of drug candidates from four major pharmaceutical companies

Michael J.Waring1, John Arrowsmith2, Andrew R.Leach3, Paul D.Leeson3,4, Sam Mandrell2, Robert M.Owen5, Garry Pairaudeau1, William D.Pennie6,7, Stephen D.Pickett3, Jibo Wang8, Owen Wallace8,9 and Alex Weir2

Abstract | The pharmaceutical industry remains under huge pressure to address the high attrition rates in drug development. Attempts to reduce the number of efficacy- and safety-related failures by analysing possible links to the physicochemical properties of small-molecule drug candidates have been inconclusive because of the limited size of data sets from individual companies. Here, we describe the compilation and analysis of combined data on the attrition of drug candidates from AstraZeneca, Eli Lilly and Company, GlaxoSmithKline and Pfizer. The analysis reaffirms that control of physicochemical properties during compound optimization is beneficial in identifying compounds of candidate drug quality and indicates for the first time a link between the physicochemical properties of compounds and clinical failure due to safety issues. The results also suggest that further control of physicochemical properties is unlikely to have a significant effect on attrition rates and that additional work is required to address safety-related failures. Further cross-company collaborations will be crucial to future progress in this area.

AstraZeneca, Alderley Park, Cheshire SK10 4TG, UK.

Thomson Reuters, 77 Hatton Garden, London EC1N 8JS, UK.

GlaxoSmithKline, Stevenage,

Hertfordshire SG1 2NY, UK.

Present address: Paul Leeson Consulting, The Malt House, Main Street, Congerstone, Nuneaton, Warwickshire CV13 6LZ, UK.

Pfizer, Cambridge, Cambridge shire CB21 6GS, UK.

Pfizer, Groton,Connecticut 06340,USA.

Present address: Takeda Pharmaceuticals, Cambridge, Massachusetts 02139, USA.

Eli Lilly, Indianapolis, Indiana 46285, USA.

Present address: Novartis Institutes for Biomedical Research, Cambridge, Massachusetts 02139, USA. Correspondence to M.J.W. email: mailto:[email protected]

Web End =mike.j.waring@ mailto:[email protected]

Web End =astrazeneca.com doi:10.1038/nrd4609 Published online 19 June 2015

Reducing the high attrition rates in drug development continues to be a key challenge for the pharmaceutical industry. The number of failures of small-molecule drug candidates due to poor pharmacokinetic profiles seems to have diminished significantly in recent years, but this has been accompanied by a shift towards failures due to efficacy and safety issues, and overall attrition rates remain high13. However, ascribing single reasons for compound failure could be an oversimplification because there may be multiple factors contributing to the decision...