Pharma-diagnostics outsourcing alliances for personalized medicine

For many years now a plethora of articles have been published in industry magazines and journals preaching that personalized medicine is not only an option but will be a requirement. Although the concept that drugs work best when targeted to specific patients is widely accepted it is not so certain that biomarkers in the form of specific molecular profiles will be an effective enough tool to accurately identify patients who will respond to a particular drug. After a decade, only the HER2Neu tests are used to determine patient selection for drug efficacy to Herceptin This is the original and essentially only drug, for which patients are selected by a diagnostic test.

There are several recent examples of EU and FDA approved commercial genomic assays especially in the oncology testing area. Examples include Genomic Health’s oncotype Dx, Aviara Diagnostics breast Cancer Reoccurrence assay, Agendia‘s Mammaprint and Applied Genomics Mammostrat. The assays from these companies all have high prognostic value applied to breast cancer reoccurrence.

They all also have their own unique and patent protected gene signatures. This information is valuable since it adds an additional management tool for the physician. However, the predictive value is limited to the practical use of ruling out (20-30%) of breast cancer patients for chemotherapy. They do not inform physicians which drug to choose to effectively treat the patient. There are no new tests associated with specific biodrugs, which with a high probability of success direct the physician to a specific therapy.
 
A good analogy presented by Dr. Richard Bender at the November 2007 AACC sponsored conference, Making the Case for New Cancer Diagnostics was his comparison of genomics testing to a swallows nest. Being from San Juan Capistrano, Dr. Bender pointed out that although every nest looks identical even from a short distance close up there are subtle differences to each and any every nest. Similarly, small genetic differences in individuals and in their diseases make a single test or single molecular profile specific for all individuals very difficult. A molecular profile that provides highly specific predictions of which drugs will be effective in all of a particular population such as breast cancer patients is still elusive.

Only very large clinical patient trials can provide enough data to identify most of these responder/non-responder profiles in order to make the test statistically useful enough with regard to specificity. When clinical drug trial data is positive, particularly in the late trial stages then partnerships with diagnostic companies are logical to successfully introduce the biomarker test into the IVD marketplace. Notable recently announced alliances, GE Global Research with Eli Lilly and Celera with Merck&Co are offered as evidence of a trend. However, these alliances are research collaborations intended to discover and develop biomarker and pharmacogenomic tests. These particular diagnostic companies may not be the best choices to bring the developed tests into the in vitro diagnostic (IVD) market.

The IVD industry consists of only about 20 sizable companies (by diagnostics standards) who constitute 80% or more of the major world markets including the US, Europe and Japan. These dominant companies are supported by hundreds of smaller companies who provide FDA and ISO 9001 produced products and services enabling the large companies to support current diagnostic test products and to develop new ones.

These supporting companies are suppliers who provide critical reagents, biochemicals and devices as well as, consulting, engineering, device, reagent, assay development and manufacturing services. These supporting companies offer pharma an opportunity to invest in biomarker development and manufacture for clinical trial use in a measured and less financially risky manner than internal investment or early stage partnerships with large diagnostic companies. Small diagnostic niche companies, which tend to have specific expertise, are more time responsive and sensitive to clients needs.

Niche experts in diagnostics can make early stage clinical trial biomarker tests to FDA and ISO quality standards inexpensively. Since new bio drugs are reported in recent years to have a FDA approval success rate of about 5% it would seem imprudent to commit large investments in biomarker development and manufacture before the drug has a high probability of approval.