ABSTRACT
The pharmaceutical industry remains under huge pressure to address the high attrition rates in drug development. Attempts to reduce the number of efficacy- and safety-related failures by analysing possible links to the physicochemical properties of small-molecule drug candidates have been inconclusive because of the limited size of data sets from individual companies. Here, we describe the compilation and analysis of combined data on the attrition of drug candidates from AstraZeneca, Eli Lilly and Company, GlaxoSmithKline and Pfizer. The analysis reaffirms that control of physicochemical properties during compound optimization is beneficial in identifying compounds of candidate drug quality and indicates for the first time a link between the physicochemical properties of compounds and clinical failure due to safety issues. The results also suggest that further control of physicochemical properties is unlikely to have a significant effect on attrition rates and that additional work is required to address safety-related failures. Further cross-company collaborations will be crucial to future progress in this area.
Subject(s)
Drug Delivery Systems/methods , Drug Discovery/methods , Drug Industry/methods , Drugs, Investigational , Animals , Drug Delivery Systems/statistics & numerical data , Drug Delivery Systems/trends , Drug Discovery/statistics & numerical data , Drug Discovery/trends , Drug Evaluation, Preclinical/methods , Drug Evaluation, Preclinical/statistics & numerical data , Drug Evaluation, Preclinical/trends , Drug Industry/statistics & numerical data , Drug Industry/trends , Drugs, Investigational/administration & dosage , Humans , Statistics as Topic/methods , Statistics as Topic/trendsSubject(s)
Clinical Trials, Phase II as Topic/trends , Clinical Trials, Phase III as Topic/trends , Early Termination of Clinical Trials/statistics & numerical data , Clinical Trials, Phase II as Topic/statistics & numerical data , Clinical Trials, Phase III as Topic/statistics & numerical data , Humans , Treatment FailureABSTRACT
Orphan drug incentives have stimulated research into diseases with significant unmet medical need. Although the targeting of orphan diseases is seen by industry as an attractive strategy, there are limited economic data available to support its use. In this paper we show that the revenue-generating potential of orphan drugs is as great as for non-orphan drugs, even though patient populations for rare diseases are significantly smaller. Moreover, we suggest that orphan drugs have greater profitability when considered in the full context of developmental drivers including government financial incentives, smaller clinical trial sizes, shorter clinical trial times and higher rates of regulatory success. The data support the targeting of rare diseases as an important component of a successful biopharma R&D strategy.
Subject(s)
Biomedical Research/economics , Drug Discovery/economics , Orphan Drug Production/economics , Clinical Trials as Topic/economics , Cost-Benefit Analysis , Drug Approval/economics , Drug Discovery/methods , Drug Discovery/organization & administration , Drug Discovery/trends , European Union , Humans , Marketing , Rare Diseases/drug therapy , Rare Diseases/economics , United States , United States Food and Drug AdministrationABSTRACT
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.