OBJECTIVE: To determine the risk of failure during drug development in castration resistant prostate cancer (CRPC) and see what factors can improve outcomes.
While several studies have performed similar methods for the industry as a whole, this is one of the first dealing exclusively with a single disease indication.
METHODS: CRPC was investigated by analyzing compounds in Phase I to Phase III clinical trials between 1998 and April 2011. Drug development failures were classified as medical or commercial and compared with industry expectations. Compounds were excluded from analysis if: their Phase I occurred before 1998; they targeted patients that were not hormone refractory; or they did not assess outcomes such as overall survival, time to disease progression, or PSA levels.
RESULTS: Thorough searches of clinicaltrial.gov and other databases yielded 77 compounds that fit the inclusion criteria. The cumulative pass rate for first line compounds in CRPC is 3% and is far below aggregate industry expectations. In total, there are nearly equivalent numbers of commercial and medical failures. Biologics have had greater relative success than small molecule drugs and biotechnology firms have been slightly more successful than pharmaceutical firms in this disease indication. Phase III failures are high despite equally high failures during phase II.
CONCLUSION: Currently, one in 33 compounds that enter clinical testing will be awarded FDA approval. This appears to be the highest risk indication investigated to date, based on clinical trial studies alone, with an average cost of $1.411 billion to bring a new drug to market when adjusted for risk. Development of radical therapeutics such as immunotherapies may also be warranted over classical antineoplastic therapeutics. Given the high clinical trial risk, efforts may have to shift to biomarker and surrogate endpoint efforts to manage future clinical trial risk in prostate cancer.
Written by:
Tenuta A, Klotz L, Parker JL. Are you the author?
Department of Biology, University of Toronto at Mississauga, Toronto, ON, Canada.
Reference: BJU Int. 2013 Jun 17. Epub ahead of print.
doi: 10.1111/bju.12309
PubMed Abstract
PMID: 24053150
UroToday.com Prostate Cancer Immunotherapy Section
