In late 2013, the FDA published Paving the Way for Personalized Medicine: FDA’s Role in a New Era of Medical Product Development, with the intention of describing the agency’s goals to help drive personalized treatments and diagnostics. Within the introduction it is stated that “elegant science” and “well-designed” personalized medicine programs have created the opportunity for the agency to streamline and expedite the approval of targeted drugs such as crizotinib, vemurafinib, dabrafenib, and tremetinib. The report proceeds to explicitly recognize that improved patient outcomes are predicated on the inseparable relationship between gene and protein diagnostic assays with therapeutic products.
Despite the extraordinary advances that have most recently resulted in the rise of the blockbuster targeted immunotherapy drugs, not all clinical programs have recognized the benefits in this approach. Since 2013 a body of research has grown specifically focused on quantifying the impact personalized medicine design has on clinical trials. The results are clear, more effective patient stratification, faster trials, and stronger data across all phases of development.
Much of the research in this area has been driven by Dr. Denis L. Jardim at the University of Texas MD Anderson Cancer Center, and Dr. Maria Schwaederle of UC San Diego’s Moores Cancer Center. The most striking and consistent benefit of adopting the targeted precision medicine design has been found in identifying highly responsive patient cohorts. Dr. Schwaederle just recently reported 30.6% vs 4.9% median response rate for Phase I biomarker-selected therapies in a poster presentation at ASCO 2016. This work built an even stronger association over a larger selection of clinical trials from the MD Anderson Initiative published in 2014. These significant improvements in patient response are carried forward into Phase II and III with 2.95x and 2.1x increases in RR, respectively.
It is well known that costs in clinical trials remain at $1.7 billion, by conservative estimates. Developing a trial design that results in the strongest possible data in terms of hazard ratios and mortality is critical to generating the successful NDAs that justify the expense. Surrogate endpoints have become an important component of developing the comprehensive value associated with new therapeutics.
Dr. Schwaederle’s meta-analysis of 570 Phase II studies indicated a 218% increase in median months of progression-free survival for targeted personalized medicine trials compared to nontargeted trials. Of course absolute survival is the most important measure for any potential new drug and personalized trials were found to also benefit overall survival by 154%.
Most strikingly, data published this July’s in Oncotarget by Dr. Jardim and colleagues has shown that targeted precision medicine studies result in an average reduction in time to NDA from 93.5 to 58.8 months. In total, the reduction in average time to FDA approval was over 25%. The resulting savings in cost due to factors such as reduced retention fees, monitoring, and administration have the potential to reach the hundreds of millions. It is understood that complex biomarker strategies are necessitating more expensive and sophisticated specialty diagnostic procedures. However the results are in and they indicate that the benefits of personalized medicine far outweigh the initial cost investment.
We always understood that precision medicine worked. Now we have the numbers to prove it.