More on New Developments at the FDA in the Era of Precision Medicine

This week the FDA approved the expanded use of the cancer drug Keytruda for any solid tumor that expresses a particular molecular marker. It is the first time that the FDA has approved new uses of a cancer drug in cancers that are defined by a molecular marker independent of the site in the body where the tumor originated. While the expanded use of the drug was based on an accelerated approval supported by surrogate markers, this is another demonstration of the FDA’s continuing adaptation to the new era of precision medicine, in which the appropriate use of a drug is defined by particular genetic and molecular markers rather than the broad traditional disease categories.

Postscript to last week’s post–– I wrote that the approval of Kalydeco for cystic fibrosis patients with 23 additional mutations was, to my knowledge, the first time ever that the FDA had approved new indications for a drug without any human clinical data. The Kalydeco label change was based entirely on an in vitro assay of the drug’s effect on the function of the cystic fibrosis transmembrane receptor. The in vitro assay had correlated well with clinical trial data from the original Kalydeco studies and provided a reasonable degree of confidence that the drug would work in the additional mutations tested. Later reports and an additional statement from the FDA confirmed my initial conclusion that this approval was indeed the first of its kind and a real breakthrough in drug approval. That is good news for the approximately 900 cystic fibrosis patients who have one of those 23 mutations. Of course the 900 patients covered by the 23 additional mutations means that there is, on average, fewer than 40 patients with any one of those mutations, which is why the FDA’s flexibility is so important. Precision medicine will need that kind of regulatory innovation to move forward when, as the FDA’s Janet Woodcock stated, there is a solid understanding of the disease’s biology, a drug with a known safety (and pharmacokinetic) profile, and a good assay to predict the drug’s effect in target populations.