Can the flow of medicines be improved? Fundamental pharmacokinetic and pharmacological principles toward improving Phase II survival.
In an effort to uncover systematic learnings that can be applied to improve compound survival, an analysis was performed on data from Phase II decisions for 44 programs at Pfizer. It was found that not only were the majority of failures caused by lack of efficacy but also that, in a large number of cases (43%), it was not possible to conclude whether the mechanism had been tested adequately. A key finding was that an integrated understanding of the fundamental pharmacokinetic/pharmacodynamic principles of exposure at the site of action, target binding and expression of functional pharmacological activity (termed together as the 'three Pillars of survival') all determine the likelihood of candidate survival in Phase II trials and improve the chance of progression to Phase III.
Pfizer, Departments of Pharmacokinetics, Dynamics and Metabolism, Ramsgate Road, Sandwich, Kent CT13 9NJ, UK.
Paul
P
Morgan
Piet H
PH
Van Der Graaf
John
J
Arrowsmith
Doug E
DE
Feltner
Kira S
KS
Drummond
Craig D
CD
Wegner
Steve D A
SD
Street
D000631:Aminopyridines / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D065100:CCR5 Receptor Antagonists; D017322:Clinical Trials, Phase II as Topic; D003510:Cyclohexanes / Q000494:pharmacology / Q000627:therapeutic use; D004341:Drug Evaluation; D015658:HIV Infections / Q000188:drug therapy / Q000378:metabolism; D006801:Humans; D000077592:Maraviroc; D009025:Morpholines / Q000494:pharmacology / Q000627:therapeutic use; D009437:Neuralgia / Q000188:drug therapy / Q000378:metabolism; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D010599:Pharmacokinetics; D050637:Receptors, Dopamine D3 / Q000819:agonists; D012735:Sexual Dysfunction, Physiological / Q000188:drug therapy / Q000378:metabolism; D014230:Triazoles / Q000494:pharmacology / Q000627:therapeutic use
D000631:Aminopyridines; D065100:CCR5 Receptor Antagonists; D003510:Cyclohexanes; D009025:Morpholines; C555358:PF 592379; D004364:Pharmaceutical Preparations; D050637:Receptors, Dopamine D3; D014230:Triazoles; D000077592:Maraviroc