Today, nearly every drug development program has a biomarker discovery project with which it is associated. In just the last five years, this has become the standard operation rather than the exception. Why has this happened so quickly? It was because we could. Technologies perfected in the 90s and early this young century have provided the opportunity to make these biomarker discoveries. In some cases it has enabled drugs to be approved that earlier would have no chance of approval. I am sure that you each know of several examples. One of the more recent is Xalkori from Pfizer for Non-Small Cell Lung Cancer (NSCLC). By identifying the ALK (anaplastic lymphoma kinase) positive fusion genotype as responders to the kinase inhibitor Xalkori (Crizotinib), this drug was approved for the 4-5% of NSCLC patients that stand a 90% chance of positive response. I have seen this effect first hand with a very close friend diagnosed with NSCLC. Fortunately, his tumor carried the ALK positive genotype and was able to receive therapy with Xalkori. The results were astounding as he went from his death bed to the golf course in just a matter of months.
This type of success story encourages all of us in this field to continue working diligently to hone and advance these technologies that are the search engines of biomarker discovery. Genotype, gene expression, protein expression as well as metabolomics have had some success. There is no “one-size fits all” approach and all should be embraced. In addition, advances in multivariate, bio-statistical data mining is advancing to meet the needs of the multiplexed biomarker world. This is essential for a struggling pharmaceutical industry as biomarker success often provides for more efficient clinical trials improving the chance of drug approval. Companion diagnostics, often the result of a successful biomarker strategy, will eventually become the norm rather than the exception. In 2013, you will start to see more of these hitting the market with an approved drug in-tow. Pharma has realized that a drug accompanied by a companion diagnostic that identifies those who will benefit most from the drug gains instant market share, albeit in a smaller market. The real struggle today is about who should fund this development; the pharma or the molecular diagnostic company? Shared risk-taking is obviously at the center of these negotiations. It will be a few more years before we see the answer to this question.
Today, we are experiencing the “era of biomarkers”. Much like the other biological discovery era such as bacteriology, virology, enzymes, monoclonal antibodies and recombinant DNA, the era of biomarkers will be defined historically over a defined timeframe. History has shown us that the vast majority of understanding and knowledge is generally acquired in the first 20 years of an “era”. I would estimate that we are about 5-7 years into the biomarker era with great opportunities in the near future. It is hard to imagine what discoveries lay ahead. It is a wonderful time to be involved with this type of cutting edge research.
Ralph L. McDade, PhD
Strategic Development Officer