Should the Food and Drug Administration (FDA) provide post-Phase 1 study accelerated review of biomarker-linked cancer medicines? In a recent, provocative article in the New England Journal of Medicine, Bruce Chabner, M.D., argues that they should. Dr. Chabner, former director of the National Cancer Institute’s Division of Cancer Treatment argues that our growing ability to target therapies to patient subgroups based on molecular or genetic diagnostics necessitates a shift to earlier approval.
In his editorial, Early Accelerated Approval for Highly Targeted Cancer Drugs, Dr. Chabner, now at Massachusetts General Hospital Cancer Center, highlights research on two targeted therapies to illustrate how biomarkers can be used to match therapies to patients most likely to benefit and/or least likely to suffer harm from an experimental treatment: PLX4032 (for patients with BRAF mutated melanoma) and crizotinib (for patients with EML4-ALK fusion in non-small cell lung cancer).
Both of these treatments were able to progress directly from Phase 1 to Phase 3 studies through use of validated biomarkers, Dr. Chabner says. But with the typical cancer drug taking seven years to complete clinical trials and gain FDA approval, the process is still “expensive and time-consuming, usually taking two to three years to reach survival end points.” In addition, phase 3 trials still require a control group to receive the standard of care, depriving some patients of the experimental treatment with potentially better response rates and less toxicity.
While other accelerated paths provide patients access to promising therapies (i.e., compassionate-use protocols and accelerated review), if we are able to define populations of patients with high response rates in phase 1 trials, prolonging drug testing and approval raises important issues. A patient with an incurable disease and the right biomarker will want access to a new therapy. Dr. Chabner argues that the new age of molecularly-guided medicine is cause for an even more rapid path to approval: “Given trialists’ ability to define patient subgroups with responsive tumors in phase 1 trials, I propose that for diseases lacking therapies that meaningfully extend survival, the FDA should set flexible standards permitting accelerated approval of new drugs after phase 1.”
Dr. Chabner’s proposal illustrates the growing and likely dramatic impact that personalized medicine will have on research and development as well as regulatory and payment standards. It also offers a potential new pathway for addressing the serious challenge of how to get potentially life-saving medications to patients as expeditiously as possible while maintaining FDA’s gold standard for safety and efficacy. His suggestion reinforces the critical need for science and policy to work hand in hand in the advancement of personalized medicine. As the science leads the way in increasing our understanding of what therapies work best for which patients, regulatory policy will need to evolve as well.