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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".

D> D> D> D> D> D> D> D> D> D> D> D> D> D> D>

Drug

Most recent basic science paper   EfficacyPatent
1albirateroneBarrie, 1994Late stage prostate cancer, survival for 15 mo compared to 11 mo.
2vemurafenibDavies, 2002Late stage melanoma, survival at 8 mo, 77% vs 64%.
3crizotinibSoda, 2007Selected lung cancers, response rate of in 57%*
4ipilimumabLeach, 1996Advanced melanoma, survival of 10 mo vs 6.5 mo.
5brentuximabTazzari, 1992Hodgkins, 73% response for 7 mo average. *
6vandetanibMarsh, 1996Median progression free survival, 23mo vs 16 mo.
7eribulinBai, 1991Metastatic breast cancer, survived 2.5 mo longer than alternate Rx
8boceprevirYan, 1998Hepatis C, sustained viral response 59% vs 21% at 48 weeks.
9telaprevirKolykhalov, 2000Hepatitis C, sustained virologic response 69% vs 44% for 48 weeks
10belimumabKhare, 2000SLE, positive clinical response 58% vs 44% at 52 weeks.
11dabigatranBrandstetter, 1992DVT, same as enoxaparin
12ticagrelorJantzen, 1999Compared to clopidogrel, CV death,CVA, & MI, 10% vs 12%
13ceftarolineTesch, 1988Community acquired pneumonia, 84% vs 78% clinical cure
14belataceptLeach, 1996Renal transplant, efficacy failure (by FDA) 29% vs 28%
15icatibant McEachern, 1991Hereditary angioedema, onset of symptoms relief 2h vs 20h
 * 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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