DNAprint Genomics (DNAG)

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Doug/frog...According to this article in Pharmalive Magazine, very few pharmaceutical companies have the core competencies necessary to develop pharmacogenomic tests to accompany their drugs. It is the opinion of the author, that they will likely partner with medical-diagnostics companies to accomplish their ends:

http://www.pharmalive.com/magazines/randd/view.cfm?articleID=1534

...The diagnostic industry is working independently of pharmaceutical companies to bring theranostics to market. Emerging pharmacogenomics technologies are presenting drug-discovery and development companies with the promise of targeted therapies and potential new revenue streams and are creating new opportunities for diagnostic companies to develop tests that can be used to determine patient response to a drug and screen out inappropriate candidates. The increasing interest in theranostics is likely to prompt more pharmaceutical companies to develop diagnostics divisions or acquire diagnostic companies. Future progress in theranostics will draw on developments in pharmacogenomics.

"There’s not an extreme urgency to develop companion diagnostics," Dr. Dorner says. "This has to be done in the next year or so and we have to hurry up and get something on the market. The whole pharmaceutical industry at this point is asking not how urgent is the need but that the need is there. Everyone believes that this is the future for the pharmaceutical industry and the questions are, ‘How can it be practically implemented? What are the technologies, and what are the time lines within the drug development pathway for accomplishing this?’ As health-care costs continue to escalate, as our drugs become more sophisticated and targeted to specific populations of patients, the need for companion diagnostics to direct therapy will become greater and greater."

FDA’s guidance on pharmacogenomic data submission will accelerate the development of theranostics. The guidance specifies when to submit pharmacogenomic data to the agency, what data to submit, and how to submit the data. These data must be focused on diagnostic tests used in conjunction with drugs and show how responses to the drug vary from person to person.

In November 2003, FDA issued a draft guidance to the pharmaceutical industry advising the companies about when to submit pharmacogenomic data to the agency during the drug’s development and review process, what formats may be used for submissions, and how the data will be used in regulatory decision making. The guidance defines pharmacogenomics as the use of a pharmacogenomic test in conjunction with therapy — an assay intended to study interindividual variations in whole-genomic or candidate gene single-nucleotide polymorphism maps, haplotype markers, and alterations in gene expression or inactivation that may be correlated with pharmacological function and therapeutic response.

The regulatory agency acknowledges that the promise of pharmacogenomics lies in its potential to individualize therapy, making it more effective while reducing its risk. FDA says the pharmacogenomic field is in its early-development stage and pharmaceutical companies are reluctant to conduct pharmacogenomic testing during the drug-development stages because they do not know how the agency will use these data in drug-application review process. The guidance was written to clarify the agency’s policy.

FDA envisions that pharmaceutical companies will begin to use pharmacogenomic tests to support drug development and/or to guide therapy. Most pharmacogenomic data are of an exploratory or research nature and are not required to be submitted. Although the submission of pharmacogenomic data is not required under FDA regulations, the agency is encouraging the voluntary submission of these data. The data can be submitted to an investigational drug application, a new drug application, or a biologics drug application. The data can be submitted to support scientific content related to dosing, safety, or efficacy. The agency will not use the information submitted for regulatory decision making but only for scientific and informational purposes.

The agency recommends joint development of the pharmacogenomic tests and the drug, and submission of complete information on the test to the agency. The agency plans to issue another guidances on joint development of pharmacogenomic tests and drugs in the near future.

Many pharmaceutical companies are using biomarkers during Phase I and Phase IIa clinical studies to predict and monitor safety and efficacy outcomes. Few pharmaceutical companies have the core capabilities, however, that would allow the development of those biomarkers into clinically validated and regulator-acceptable surrogate markers of disease outcomes, thus time and costs savings are not yet realized in Phase IIb and Phase III registration studies. Pharmaceutical companies, with their access to large numbers of patients who have undergone therapy with proprietary medicines, represent a resource that can be used to validate biomarkers. In collaboration with a medical-diagnostics company, they can jointly develop these validated biomarkers into a medical-diagnostic test.

Right now, only a few pharmacogenomic tests for certain drug-metabolizing enzymes are considered valid biomarkers in humans. FDA is encouraging pharmaceutical companies to develop pharmacogenomic tests that predict which subpopulations will have a positive response to therapy. Regulators point to the trend that has emerged in the past few years of drug labels becoming more narrow in their indications. The shift has become apparent in the HIV-drug-therapy field, which evolved from broad indications to narrow indications when the drug-resistance tests became available.

The agency is particularly interested in receiving pharmacogenomic data that distinguish patients at greater risk for a serious adverse event, and exploring the correlation in the appropriate populations. For pharmaceutical companies interested in developing the drug solely for populations that exclude the high-risk patients based on pharmacogenomic testing, the agency recommends that the company jointly develop a diagnostic and the drug because the agency would be unable to prove a drug for which the safety profile was predicated on a pharmacogenomic test that was unavailable.

FDA envisions that in the future, pharma-cogenomic markers that predict drug toxicity will be identified and developed on a parallel path with overall drug development. The medicine would be developed in a conventional manner with a parallel effort to identify appropriate predictors of toxicity. If the drug’s risk-benefit profile were acceptable, the drug could be approved before the completion of efforts to refine and develop the relevant pharmacogenomic tests. When the predictive value of a diagnostic test is to be established and the test is to become commercially available, the drug label could be changed to reflect the data.

FDA is countering the perception that pharmacogenomic testing is likely to give very definitive answers about safety and effectiveness in subpopulations. This may happen sometimes, as it happens in oncology, and in these cases the rapid development of a diagnostic test is highly encouraged. This is unlikely, the agency says, to be the ordinary case. In most instances, the gene expression profile is likely to be one of a number of factors.

"FDA had a workshop in March on the concept of how to codevelop a diagnostic assay for pharmacogenomics or pharmaco-
genetics data and a drug and a companion diagnostic should be developed simultaneously, but I am not sure that is possible," Dr. Dorner says. "In most cases, biomarkers for the diagnostic will be identified or will be discovered in a Phase II clinical trial because many times the Phase I clinical trial is healthy volunteers and it isn’t always a diseased population that is going to be targeting in the later-stage trials. In many cases, we will be discovering biomarkers in Phase II to put together an assay to be validated in Phase III and then go to the FDA for registration of the drug as well as some information on what the companion diagnostic should be.

"At this point, we are going to have to develop, perhaps, new paradigms of how to jointly develop a diagnostic that can be used in the label to determine patient-therapeutic options. That is something that FDA is very interested in, understanding how to do this."

Industry observers say the era of the blockbuster market is over. Although there will be more blockbusters, there are not enough blockbusters left to fuel the entire pharmaceutical industry. The innovation in the industry has been more and more in targeted therapies.

"This is a good trend," Dr. Cohen says. "Targeted therapies will allow for many indications and will allow us as physicians to offer better and safer medications over time. We will not have personalized medicine tomorrow, but during the next decade there will be an explosion in the number of drug-development programs that utilize pharmacogenetic-companion tests. This is a natural evolution of molecular medicine."

BTW, isn't that a most interesting definition of Pharmacogenomics:

The guidance defines pharmacogenomics as the use of a pharmacogenomic test in conjunction with therapy — an assay intended to study interindividual variations in whole-genomic or candidate gene single-nucleotide polymorphism maps, haplotype markers, and alterations in gene expression or inactivation that may be correlated with pharmacological function and therapeutic response.


Later,
W2P