Marcus M. Reidenberg, MD, FACP


NOTES ON THERAPEUTICS
These notes are commentaries giving an individual healthcare expert's perspective on issues having to do with approved drugs and devices. They were created to provide patients, caregivers, and healthcare professionals with evidence-based information and opinions about important therapeutic issues. New notes are added periodically. The Notes may be printed and distributed to patients and anyone else who may find them helpful.



"FDA petition asking for warning"

Science 28 September 2012: Vol. 337 no. 6102 p. 1605

U.S. Basic Research: Delayed Drug Development


Related Resources In Science Magazine

Editorial EDITORIAL: NIH Basics Francis S. Collins Science 3 August 2012: 503.


In his Editorial "NIH Basics" (3 August, p. 503), F. S. Collins articulates the need for continued support of basic research by the U.S. National Institutes of Health (NIH) to enable future therapeutic discoveries. We have gathered more information about the relationship between basic research and new drugs. In 2011, the Food and Drug Administration (FDA) approved 17 new drugs that were considered notable therapeutic advances (1). We reviewed the reference lists from publications about these drugs to determine the most recent basic science paper that contributed to the drug's development. We defined basic science papers as leading to understanding or description of a biologic process without studying any drug candidate. The publication dates of the most recent basic papers for each of the 15 drugs reviewed (two drugs approved in 2011 were excluded) ranged from 1988 to 2007, with a median of 1996 (2). Eight of the 15 papers were from U.S. labs. The earliest patent in the FDA Orange Book for each of the 15 drugs averaged 2 years after the most recent basic paper. Interest in developing these drugs may have preceded the most recent basic publications. An outsider cannot know how important these recent papers were in the decision-making for developing these drugs. Despite these caveats, our findings are consistent with other data showing the delay between basic research and applied results. Paul et al. cite an average duration of 13.5 years for drug development after a drug target has been fully identified and validated (3). The 16-year median interval from the most recent basic paper to drug approval fits with this duration of specific drug development and illustrates the need to shorten the drug development process. It confirms the importance of basic research now for therapeutic advances in the intermediate as well as the long-term future.

Appendix to letter, NIH Basics in Science


Table 1. Latest basic science publication related to development of 15 drugs approved by FDA in 2011 considered providing "significant contributions to the health of patients".

Drug

Most recent basic science paper   Efficacy Patent
1 albiraterone Barrie, 1994 Late stage prostate cancer, survival for 15 mo compared to 11 mo. 1994
2 vemurafenib Davies, 2002 Late stage melanoma, survival at 8 mo, 77% vs 64%. 2006
3 crizotinib Soda, 2007 Selected lung cancers, response rate of in 57%* 2005
4 ipilimumab Leach, 1996 Advanced melanoma, survival of 10 mo vs 6.5 mo. -
5 brentuximab Tazzari, 1992 Hodgkins, 73% response for 7 mo average. * -
6 vandetanib Marsh, 1996 Median progression free survival, 23mo vs 16 mo. 1997
7 eribulin Bai, 1991 Metastatic breast cancer, survived 2.5 mo longer than alternate Rx 1999
8 boceprevir Yan, 1998 Hepatis C, sustained viral response 59% vs 21% at 48 weeks. 2002
9 telaprevir Kolykhalov, 2000 Hepatitis C, sustained virologic response 69% vs 44% for 48 weeks 2005
10 belimumab Khare, 2000 SLE, positive clinical response 58% vs 44% at 52 weeks. -
11 dabigatran Brandstetter, 1992 DVT, same as enoxaparin -
12 ticagrelor Jantzen, 1999 Compared to clopidogrel, CV death,CVA, & MI, 10% vs 12% 1998
13 ceftaroline Tesch, 1988 Community acquired pneumonia, 84% vs 78% clinical cure 1998
14 belatacept Leach, 1996 Renal transplant, efficacy failure (by FDA) 29% vs 28% -
15 icatibant McEachern, 1991 Hereditary angioedema, onset of symptoms relief 2h vs 20h 1994
 * trials without concurrent controls

Efficacy was from the FDA publication (2) or a representative clinical trial.

Most recent basic science papers references:

  • Albiraterone: Barrie SE. J Steroid Biochem Molec Biol 50, 267 (1994)
  • Vemurafenib: Davies H. Nature 417, 949 (2002)
  • Crizotinib: Soda M. Nature 448, 561 (2007)
  • Ipilimumab: Leach DR. Science 271, 1734 (1996)
  • Brentuximab: Tazzari PL. Br J Haematol 81, 203 (1992)
  • Vandetanib: Marsh DJ, Clin Endocrinol 44, 249 (1996)
  • Eribulin: Bai R, J Biol Chem 266, 15882 (1991)
  • Boceprevir: Yan Y, Protein Science 7, 837 (1998)
  • Telaprevir: Kolykhalov AA. J Virol 74, 2046 (2000)
  • Belimumab: Khare SD, PNAS 97, 3370 (2000)
  • Dabigatran: H Brandstetter, et al., J Mol Biol 226, 1085 (1992)
  • Ticagrelor: H-M Jantzen, et al., Thromb Haemost 81, 111 (1999)
  • Ceftaroline: W Tesch, et al., Antimicrob Agents Chemotherapy 32, 1494 (1988)
  • Belatacept: Tesch, op cit
  • Icatibant: AE McEachern, et al., PNAS 88, 7724 (1991)

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