Reducing attrition in drug development: smart loading preclinical safety assessment

Research output: Contribution to journalReview articlepeer-review

Authors

  • Stefan Kavanagh
  • Howard R. Mellor
  • Christopher E. Pollard
  • Sally Robinson
  • Stefan J. Platz

Colleges, School and Institutes

External organisations

  • AstraZeneca R&D

Abstract

Entry into the critical pre-clinical ‘Good Laboratory Practice (GLP)’ stage of toxicology testing triggers significant R&D investment yet >20% of AstraZeneca’s potential new medicines have stopped for safety reasons in this GLP phase alone. How could we avoid at least some of these costly failures? An analysis of historical ‘stopping toxicities’ showed that > 50% were attributable to target organ toxicities emerging within two weeks of repeat dosing or to acute cardiovascular risks. By frontloading 2 week repeat dose toxicity studies and a comprehensive assessment of cardiovascular safety, we anticipate a potential 50% reduction in attrition in the GLP phase. This will reduce animal use overall, save significant R&D costs and improve drug pipeline quality.

Details

Original languageEnglish
Pages (from-to)341-347
Number of pages6
JournalDrug Discovery Today
Volume19
Issue number3
Early online date21 Nov 2013
Publication statusPublished - 1 Mar 2014