I-SPY and now AGILE Cancer Programs

By Harley Everett Wilcox, MBA

Senior Scientific Advisor

ABC Laboratories
www.abclabs.com

Historical clinical cancer studies lack efficiency and require significant time for often an overall survival improvement of only 60 days versus standard treatment. The inefficiencies may be related to the need for adequate safety evaluation, single agent studies, and limited tumor biological information for individual patients.  Approval of a new oncological agents require 10-15 years of clinical drug development and in rarer cancers, patient populations available for study are lacking .New investigation drugs require evaluation in diseased patients prior to approval and often before combination with other attractive agents. With the advancements in biological test procedures, and better understanding of cancer biology, an individual tumor may be profiled to determine the theoretical optimum drugs, combination of drugs and dosing schedule.

The I-SPY program is a novel personalized cancer treatment study supported by the FDA, NIH and a consortium of pharmaceutical companies via the Foundation for the National Institutes of Health (FNIH). The design allows for investigating new drug therapies with standard treatment and flexibility to modify treatment protocols on the fly, saving time, money, and optimal treatment regimens for breast cancer patients.  Multiple company intellectual property have been combined in a single phase II like program to access the best therapy based on tumor biology and proof concept of activity prior to surgery in resistant tumor types. The goal will be to bring effective treatments to market with fewer patients and in less time.  

Targeting another type of cancer in an adaptive trial approach is MD Anderson and the recently announced AGILE study.  Glioblastoma multiform has yet to see a new chemical treatment option in ~10 years with the standard chemotherapy Tremodar and radiation providing an overall survival improvement of just 2 months.  MD Andersons’ Mitchel Burger, MD states the uniqueness of the study, like the I-SPY uses biological tumor profiling and Bayesian statistics to limit the number of clinical patients.  The statistical method allow for a probability approach to advance drug winners more quickly. As stated earlier, one issue with rare cancers is adequate patient populations for supporting multiple clinical studies. With~10,000 GBM cases a year combined with aggressive disease, brain cancer clinical programs often require longer time to complete enrollment.

These adaptive clinical trial programs will hopefully provide more meaningful outcome for clinical trial participants and more rapid approval for needed treatment options.

References:

http://ispy2.org

Target Oncology (targetdonc.com)

21st Century Cures Act – Is It Truly Progress?

By Glenn Petrie, Ph.D.
Senior Scientific Advisor
ABC Laboratories
www.abclabs.com

Dr. Francis Collins, Director of NIH, has stated that it takes “around 14 years and $2 billion or more “to develop a new drug. Based on statements like these, Congress has come to the conclusion that the drug approval process is too onerous and lengthy and is the primary impediment to the discovery and approval of new drugs. In response they have passed the 21^st Century Cures Act with nearly unanimous, bipartisan approval. But is this a fallacious assumption? Some argue that the FDA review and approval process is the fastest and most streamlined in the world and that accelerating the approval process may impact patient safety.

In an editorial in the New England Journal of Medicine, Dr. Jerry Arvon states ”The bill would also encourage the FDA to rely more on biomarkers and other surrogate measures rather than actual clinical end points in assessing the efficacy of both drugs and devices.” While surrogates have previously been utilized as endpoints by the FDA to support accelerated approvals, this was only for drugs intended to treat life threatening illnesses.  Dr. Arvon goes on to state that biomarkers “may not always predict the drug’s capacity to improve patient outcomes “. The literature has many examples of cancer drugs approved utilizing these criteria that not only do not extend life, but have side effects.

While the argument regarding expedited drug approval continues, one aspect of the new law has unanimous support; an additional $8.75 billion in funding for NIH over the next 5 years.  According to a study published in Health Affairs, federal funding of basic research played a major role in the origin of transformative drugs approved between 1984 and 2009.