Sunday, December 4, 2011

28% of Phase III Failures are in Oncology Trials

John Arrowsmith of Thomson Reuters, who described these numbers in a Nature Reviews Drug Discovery article, listed three major reasons for Phase III failures in oncology:

(1) lack of a complete understanding of relevant pathways and target biology, 
(2) over-optimism and wishful thinking by drug companies who in their eagerness to replenish pipelines rush into Phase III on the back of less-than-robust Phase II or proof-of-concept data, and 
(3) assumption that a drug working in one cancer-type has a high chance of success in another type of cancer.  Executives pushing the envelope sometimes overlook the fact that cancer is a heterogeneous disease.  For example, inspite of finding a similar molecular driver, cancer of lung would be as different from renal cancer as baseball is from cricket--two classic examples are sunitinib (Sutent, Pfizer) and bevacizumab (Avastin, Genentech) failures in hepatic and gastric cancers, respectively.  The Phase III failures were due to lack of efficacy (66%) or toxicity (21%).  This article did not say what percent of all oncology trials fail or pass?  Below are some additional numbers.
  • Only 34% of cancer drugs tested between 2003 and 2010 passed Phase III hurdle (see Barry 2011). 
  • According to BIO (Biotechnology Industry Organization) the Phase II success rate of oncology drugs between 2003 and 2010 was 29%.  And the overall success rate from Phase I to Market was 11%, and only 2% for those tested for secondary indication passed. (read at Internal Medicine News Feb. 2011).
  • However, about 800 anti-cancer drugs are inn development which represents a 143% increase over the last decade (Arrondeau et al. Discovery Medicine. October 26, 2010).

Arrowsmith J (2011). Trial watch: phase III and submission failures: 2007-2010. Nature reviews. Drug discovery, 10 (2) PMID: 21283095 | DOI |

Berry DA (2011). Adaptive clinical trials in oncology. Nature reviews. Clinical oncology PMID: 22064459

Kola, I., & Landis, J. (2004). Opinion: Can the pharmaceutical industry reduce attrition rates? Nature Reviews Drug Discovery, 3 (8), 711-716 DOI: 10.1038/nrd1470

1 comment:

  1. Excellent explanation,
    I appreciate your writings. job well done.