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Lessons learned from the fate of AstraZeneca's drug pipeline: a five-dimensional framework

Abstract

Maintaining research and development (R&D) productivity at a sustainable level is one of the main challenges currently facing the pharmaceutical industry. In this article, we discuss the results of a comprehensive longitudinal review of AstraZeneca's small-molecule drug projects from 2005 to 2010. The analysis allowed us to establish a framework based on the five most important technical determinants of project success and pipeline quality, which we describe as the five 'R's: the right target, the right patient, the right tissue, the right safety and the right commercial potential. A sixth factor — the right culture — is also crucial in encouraging effective decision-making based on these technical determinants. AstraZeneca is currently applying this framework to guide its R&D teams, and although it is too early to demonstrate whether this has improved the company's R&D productivity, we present our data and analysis here in the hope that it may assist the industry overall in addressing this key challenge.

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Figure 1: Overview of project success rates and reasons for closure.
Figure 2: Analysis of project closures due to safety issues.
Figure 3: Analysis of project closures due to efficacy issues.
Figure 4: Analysis of patient selection and commercial positioning.
Figure 5: The 5R framework.
Figure 6: Analysis of back-up candidate drugs.

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Acknowledgements

The authors would like to thank S. Curran, J. Curwen, U. Eriksson, G. Johnston, R. Maciewicz, J. Munroe, M. Needham, P. Newham, W. Redfern, M. Snowden, F. Tierney, J.-P. Valentin and J. Waterton for their help in producing and reviewing this manuscript.

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Correspondence to Menelas N. Pangalos.

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All authors are employees and shareholders of AstraZeneca.

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Cook, D., Brown, D., Alexander, R. et al. Lessons learned from the fate of AstraZeneca's drug pipeline: a five-dimensional framework. Nat Rev Drug Discov 13, 419–431 (2014). https://doi.org/10.1038/nrd4309

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