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A decade of innovation in pharmaceutical R&D: the Chorus model

Abstract

Chorus is a small, operationally independent clinical development organization within Eli Lilly and Company that specializes in drug development from candidate selection to clinical proof of concept. The mission of Chorus is to achieve proof of concept rapidly and at a low cost while positioning successful projects for 'pharma-quality' late-stage development. Chorus uses a small internal staff of experienced drug developers and a network of external vendors to design and implement chemistry, manufacturing and control processes, preclinical toxicology and biology, and Phase I/II clinical trials. In the decade since it was established, Chorus has demonstrated substantial productivity improvements in both time and cost compared to traditional pharmaceutical research and development. Here, we describe its development philosophy, organizational structure, operational model and results to date.

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Figure 1: The quick-win, fast-fail model.
Figure 2: Summary of characteristics of the Chorus portfolio.
Figure 3: Time and cost of Chorus programmes.
Figure 4: Ten years of portfolio flow through Chorus.

References

  1. 1

    Munos, B., Lessons from 60 years of pharmaceutical innovation. Nature Rev. Drug Discov. 8, 959–968 (2009).

    CAS  Article  Google Scholar 

  2. 2

    Paul, S. M. et al. How to improve R&D productivity: the pharmaceutical industry's grand challenge. Nature Rev. Drug Discov. 9, 203–214 (2010).

    CAS  Article  Google Scholar 

  3. 3

    Dimitri, N. An assessment of R&D productivity in the pharmaceutical industry. Trends Pharmacol. Sci. 32, 683–685 (2011).

    CAS  Article  Google Scholar 

  4. 4

    Pammolli, F., Laura Magazzini, L. & Massimo Riccaboni, M. The productivity crisis in pharmaceutical R&D. Nature Rev. Drug Discov. 10, 428–438 (2011).

    CAS  Article  Google Scholar 

  5. 5

    Scannell, J. W., Blanckley, A., Boldon, H. & Warrington, B. Diagnosing the decline in pharmaceutical R&D efficiency. Nature Rev Drug Discov. 11, 191–200 (2012).

    CAS  Article  Google Scholar 

  6. 6

    McAndrews, P. Lilly sings a new tune: Chorus unit brings high efficiency note to early R&D. The Pink Sheet 69, 26 (2007).

    Google Scholar 

  7. 7

    Longman, R. Lilly's Chorus experiment. In Vivo 25, 1–5 (2007).

    Google Scholar 

  8. 8

    Bonabeau, E. N., Bodick, N. & Armstrong, R. W. A more rational approach to new-product development. Harv. Bus. Rev. 86, 96–102 (2008).

    PubMed  Google Scholar 

  9. 9

    Ringel, M., Tollman, P., Hersch, G. & Schulze, U. Does size matter in R&D productivity? If not, what does? Nature Rev. Drug Discov. 12, 901–902 (2013).

    CAS  Article  Google Scholar 

  10. 10

    Cook, D. et al. Lessons learned from the fate of AstraZeneca's drug pipeline: a five-dimensional framework. Nature Rev. Drug Discov. 13, 419–431 (2014).

    CAS  Article  Google Scholar 

  11. 11

    Bouchie, A. Lilly's new operating system. BioCentury A7–A8 (2009).

  12. 12

    An audience with... Steven Paul. Nature Rev. Drug Discov. 8, 14 (2009).

  13. 13

    Morgan, P. et al. Can the flow of medicines be improved? Fundamental pharmaocokinetic and pharmacodynamic principles toward improving Phase II survival. Drug Discov. Today 17, 419–424 (2012).

    CAS  Article  Google Scholar 

  14. 14

    Cartwright, M. E. et al. Proof of concept: a PhRMA position paper with recommendations for best practice. Clin. Pharmacol. Ther. 87, 278–285 (2010).

    CAS  Article  Google Scholar 

  15. 15

    McNamee, P. & Celona, J. Decision Analysis for the Professional 4th edn (Smartorg Inc., 2005).

    Google Scholar 

  16. 16

    Genovese, M. C. et al. LY2439821, a humanized anti–interleukin-17 monoclonal antibody, in the treatment of patients with rheumatoid arthritis. Arthritis Rheum. 62, 929–939 (2010).

    CAS  Article  Google Scholar 

  17. 17

    Genovese, M. C. et al. Tabalumab in rheumatoid arthritis patients with an inadequate response to methotrexate and naive to biologic therapy. Arthritis Rheum. 65, 880–889 (2013).

    CAS  Article  Google Scholar 

  18. 18

    Dodick, D. W. et al. Safety and efficacy of LY2951742, a monoclonal antibody to calcitonin gene-related peptide, for the prevention of migraine: a phase 2, randomised, double-blind, placebo-controlled study. Lancet Neurol. 13, 885–892 (2014).

    CAS  Article  Google Scholar 

  19. 19

    Raddad, E. et al. Pharmacometric analyses to support early development decisions for LY2878735: a novel serotonin norepinephrine reuptake inhibitor. CPT Pharmacometrics Syst. Pharmacol. 2, e66 (2013).

    CAS  Article  Google Scholar 

  20. 20

    Sloan-Lancaster, J. et al. Double-blind, randomized study evaluating the glycemic and anti-inflammatory effects of subcutaneous LY2189102, a neutralizing IL-1β antibody, in patients with type 2 diabetes. Diabetes Care 36, 2239–2246 (2013).

    CAS  Article  Google Scholar 

  21. 21

    Bihorel, S. et al. Population pharmacokinetic modeling of LY2189102 after multiple intravenous and subcutaneous administrations. AAPS J. 16, 1009–1017 (2014).

    CAS  Article  Google Scholar 

  22. 22

    Galsky, M. D. et al.A Phase I trial of LY2510924, a CXCR4 peptide antagonist, in patients with advanced cancer. Clin. Cancer Res. 20, 3581–3588 (2014).

    CAS  Article  Google Scholar 

  23. 23

    Adams, C. and Brantner, V. Spending on new drug development. Health Econom. 19, 130–141 (2010).

    Article  Google Scholar 

  24. 24

    Mestre-Ferrandiz, J., Sussex, J. & Towse, A. The R&D Cost of a New Medicine (Office of Health Economics, 2012).

    Google Scholar 

  25. 25

    Christensen, C. The Innovators Dilemma (Harvard Business Review Press, 1997).

    Google Scholar 

  26. 26

    Garnier, J. P. Rebuilding the R&D engine in big pharma. Harv. Bus. Rev. 86, 68–76 (2008).

    Google Scholar 

  27. 27

    Moran, N. Public sector seeks to bridge 'valley of death'. Nature Biotech. 25, 266 (2007).

    CAS  Article  Google Scholar 

  28. 28

    Larsen, C. M. et al. Interleukin-1–receptor antagonist in type 2 diabetes mellitus. N. Engl. J. Med. 356, 1517–1526 (2007).

    CAS  Article  Google Scholar 

  29. 29

    Larsen, C. M. et al. Sustained effects of interleukin-1 receptor antagonist treatment in type 2 diabetes. Diabetes Care 32, 1663–1668 (2009).

    CAS  Article  Google Scholar 

  30. 30

    Donath, M. Y. et al. XOMA 052, an anti-IL-1β antibody, in a double blind, placebo controlled, dose escalation study of the safety and pharmacokinetics in patients with type 2 diabetes mellitus — a new approach to therapy. Diabetologia 51, S1–S588 (2008).

    Article  Google Scholar 

Download references

Acknowledgements

Since its inception in 2002, Chorus has benefited enormously from the people of Chorus, both past and present. This story would not have been possible without the vision, leadership, creativity, passion and talent of so many people. We gratefully acknowledge and thank them all for their contributions. Our story would also not be possible without our many collaborators and partners: external vendors, consultants, key opinion leaders and clinical trial site staff are all part of the Chorus story and we thank them too. A key part of our success has also relied on visionaries and leaders within Lilly; we thank our key supporters for many years of continued collaboration. Particular recognition is deserved by A. Bingham, N. Bodick and M. Clayman who originated, advanced and nurtured the original Chorus concept. I. Wilding, A. Schacht, S. Paul and the referees are gratefully acknowledged for contributions to this manuscript.

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Correspondence to Paul K. Owens.

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Owens, P., Raddad, E., Miller, J. et al. A decade of innovation in pharmaceutical R&D: the Chorus model. Nat Rev Drug Discov 14, 17–28 (2015). https://doi.org/10.1038/nrd4497

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