title: An analysis of the attrition of drug candidates from four major pharmaceutical companies.
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.
authors.affiliation: AstraZeneca, Alderley Park, Cheshire SK10 4TG, UK.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Waring
authors.affiliation: Thomson Reuters, 77 Hatton Garden, London EC1N 8JS, UK.
authors.forename: John
authors.initials: J
authors.lastname: Arrowsmith
authors.affiliation: GlaxoSmithKline, Stevenage, Hertfordshire SG1 2NY, UK.
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Leach
authors.affiliation: 1] GlaxoSmithKline, Stevenage, Hertfordshire SG1 2NY, UK. [2] Paul Leeson Consulting, The Malt House, Main Street, Congerstone, Nuneaton, Warwickshire CV13 6LZ, UK.
authors.forename: Paul D
authors.initials: PD
authors.lastname: Leeson
authors.affiliation: Thomson Reuters, 77 Hatton Garden, London EC1N 8JS, UK.
authors.forename: Sam
authors.initials: S
authors.lastname: Mandrell
authors.affiliation: Pfizer, Cambridge, Cambridgeshire CB21 6GS, UK.
authors.forename: Robert M
authors.initials: RM
authors.lastname: Owen
authors.affiliation: AstraZeneca, Alderley Park, Cheshire SK10 4TG, UK.
authors.forename: Garry
authors.initials: G
authors.lastname: Pairaudeau
authors.affiliation: 1] Pfizer, Groton, Connecticut 06340, USA. [2] Takeda Pharmaceuticals, Cambridge, Massachusetts 02139, USA.
authors.forename: William D
authors.initials: WD
authors.lastname: Pennie
authors.affiliation: GlaxoSmithKline, Stevenage, Hertfordshire SG1 2NY, UK.
authors.forename: Stephen D
authors.initials: SD
authors.lastname: Pickett
authors.affiliation: Eli Lilly, Indianapolis, Indiana 46285, USA.
authors.forename: Jibo
authors.initials: J
authors.lastname: Wang
authors.affiliation: 1] Eli Lilly, Indianapolis, Indiana 46285, USA. [2] Novartis Institutes for Biomedical Research, Cambridge, Massachusetts 02139, USA.
authors.forename: Owen
authors.initials: O
authors.lastname: Wallace
authors.affiliation: Thomson Reuters, 77 Hatton Garden, London EC1N 8JS, UK.
authors.forename: Alex
authors.initials: A
authors.lastname: Weir
mesh_terms: D000818:Animals; D016503:Drug Delivery Systems / Q000379:methods* / Q000706:statistics & numerical data / Q000639:trends; D055808:Drug Discovery / Q000379:methods* / Q000706:statistics & numerical data / Q000639:trends; D004353:Drug Evaluation, Preclinical / Q000379:methods / Q000706:statistics & numerical data / Q000639:trends; D004345:Drug Industry / Q000379:methods* / Q000706:statistics & numerical data / Q000639:trends; D015507:Drugs, Investigational / Q000008:administration & dosage; D006801:Humans; D013223:Statistics as Topic / Q000379:methods / Q000639:trends
chemical_list: D015507:Drugs, Investigational