January 1, 1970 (Vol. , No. )

Rod Raynovich

In the October 1 issue of GEN I wrote a review of the impact of genomics in diagnostics and the potential of companion diagnostics or the synergy of diagnostics with therapeutics. Biomarkers will continue to be a hot topic.

Recent scientific developments in genomics and the success of companies such as Myriad Genetics (MYGN) and Genomic Health (GHDX) is the beginning of a trend where better diagnostics (such as biomarkers) will bring more cost effective targeted therapeutics. At Monday’s BIO Breakout Session at 4 pm, a packed room of over 100 scientists and business executives were seeking solutions as to how biomarkers might evolve. The panel moderator Eileen Smith Ewing of K&L/Gates queried entrepreneur Mara Aspinwall, former President of Genzyme Genetics, and Bob Goodenow, President and CEO of Syndax, a cancer therapy company both who believe in the opportunity for the sector.

The subject proved to be quite daunting because of the regulatory issues, clinical study requirements and business model differences between pharma and diagnostics. The FDA provided limited guidelines in 2005 under 21 CFR 3.2(e) that offered the option to pursue a combo biomarker test with a drug or as a stand-alone. The clinical studies and regulatory pathway is infinitely more complex with the “combo test” moreover a business partnership must also be structured. The best market opportunities were thought to be in cancer and infectious disease. For example there is already a demonstrated need for biomarkers with HER2 for colon cancer. There are a number of successful business models that link diagnostics and drugs but not with molecular tests.

A brief case study that can help elucidate the advantages of Dx/Rx linkage is that of that of bone metabolism drugs such as Fosamax (Merck) for osteoporosis and diagnostic bone x-rays (densitometry), which was a marketing and clinical win for both sides. The success was due to the need for a baseline bone measurement in order to prescribe Fosamax a drug that helps reduce bone loss. Key points were the high reimbursement for the diagnostic x-ray in excess of $150 and the strong marketing collaboration among the players.

The conspiracy theory surrounding biomarker development is that the drug companies are stalling on companion diagnostics because they don’t want to run the risk of delaying drug development or having to share royalties with a Dx partner. Moreover it was pointed out that drugs in general are only 30-60% effective so it might expose the weak efficacy of some drugs. (There were no large pharmaceutical companies on the panel but many in the audience). Nonetheless many large drug companies are implementing this strategy such as Roche.

With current biotechnology drugs in the cancer area two markers have shown promise: the HER2 test used with Herceptin therapy and the Kras test used with Erbitux. These genetic tests can identify patients who are likely to be best responders with these drugs.

Some of the issues summarized by both Goodenow and Aspinwall that are key to the linkage of drugs and diagnostics:

1.) Valuable patient samples obtained by drug companies can be provided to biomarker studies to validate clinical utility and efficacy.

2.) Higher reimbursement of biomarker diagnostics in the long run would spur development and help prove drug efficacy.

3.) Drugs may actually be approved sooner with good biomarker data.

4.) A new regulatory pathway and standard may be needed for biomarkers because the current system of PMA’s and 510k’s does not fit.

5.) Drug pricing and reimbursement models can be tailored based upon survival or efficacy data.

6.) Biomarker test revenue will not accelerate without citation in the drug label as a clinical requirement.

7.) The current business model might need modification such as the Rx company managing the distribution of a biomarker.

8.) With the exception of a few large integrated Dx/Rx companies there is business culture conflict between Dx and Rx.

9.) Support for use of biomarkers have come from ASCO and European regulatory authorities.

There are many sources of information on biomarkers and this year’s BIO has several sessions. For example Kevin Wang, CSO of Banyan Biomarkers, will present neuroproteomic and systems biology based tests for traumatic brain injury. Over 200 molecular biomarkers are in various stages of development and data is being published on their ability to predict therapeutic response. The collaboration and clinical linkage of diagnostics and therapeutics for safer and more effective drugs is intuitive and inevitable.

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