Thursday, August 18, 2011

Biomarkers: One Step Closer to Bureaucracy and This is a Good Thing (No, Really)

The FDA issued its recommendations on August 10, 2011 for biomarker approval. As expected, the FDA wants to find a clear standard for biomarker approval but also indicates that it will be hard to identify consistent and clear standards. This may seem a bit discouraging. The committee—going by the oh-so-jaunty title of Efficacy Working Group of the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use—does want to establish guidelines that will result in standardized structure for genomic biomarker submission. The committee acknowledged that its recommendations are based on its experiences with previous submissions. Much of the its previous experience in this area is either with a single biomarker or a large scale assay used as a product-marketing application. In other words, the FDA has the best intentions but no significant clarity on the best unified approach to submissions going forward. It is clear, however, that the FDA has faith in the utility of biomarkers (as yet largely untapped) to add substantially to the drug development process from discovery to post-marketing. This is an improvement over the not-so-distant days of having to fight the FDA to consider biomarker data. So, what’s next?

The heart of the matter is how to prove the value of biomarkers throughout the pipeline-from discovery through treatment of targeted populations. There is hope. Earlier this week, Roche and partner Daichii Sankyo received early FDA approval (2 months ahead of PDUFA date) for Zelboraf to be used for the treatment of metastatic melanoma. Zelboraf targets the mutated BRAF gene and has a companion diagnostic, which was approved simultaneously. In clinical trials, Zelboraf was shown to reduce the risk of death by 64%.  By any measure, this is significant – especially in the cancer world. The success in the clinic, which led to early approval, represents a substantive step forward in personalizing treatment for certain cancers. Biomarkers played a role here—particularly the biomarker that indicates mutations in the BRAF gene. Zelbroaf, though sales are estimated to perhaps be a bit lighter than for BMS’s Yervoy, is expected to be a blockbuster. (Analyst and industry consensus for total peak revenues for Yervoy is just over US$1billion, while early consensus for Zelboraf point to US$735 million by 2015. Potential peak revenues could be as high as US 1.5 billion but there is not yet a consensus.) Its companion test will sell for US$150. On a side note, the companies plan to explore whether these two compounds work well together.

Biomarkers remain a bit of a dark horse as far as smooth approval processes goes, but there is progress being made. Biomarkers are being used as an Alzheimer’s early detection tool, for ovarian and prostate cancer and many other disease areas. Researchers and companies already know what the FDA just stated…..  it is not a walk in the park to come up with “consistent standards” that will add structure but still be flexible enough for specific characteristics of the biomarkers in each submission.    

As in nearly everything else to do with biotech, research and even bureaucracy—patience and perseverance will be the key. These recommendations, despite focus on data format and a structure checklist, are a step forward in this evolving situation.

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