Biomarker Development CNS
PGxHealth’s has developed industry leading know-how and experience in translating the science relating to genetic marker discovery to valuable applications in the clinical setting. The division is accustomed to discovering and in-licensing proprietary markers including but not limited to those in CNS, cardiovascular, oncology. Once the genetic marker is known, and clinical utility is evident, PGxHealth has the experience to validate and commercialize genetic tests based on these markers. The genetic markers that are developed and included in PGxHealth’s test catalog are chosen for commercialization based PGxHealth’s assessment of their economic and clinical value to the key consumers of these tests (including patients, providers, payers). In addition, we work directly with those developing therapeutics to identify genetic markers, incorporate the markers into their commercialization plan, and PGxHealth is positioned to commercialize the resultant genetic tests for our clients as well in the same manner we commercialize our own genetic tests. PGxHealth is committed to funding its in licensing, development and commercialization of these genetic tests but will continue to work with others to accelerate discovery and development where a strategic fit exists.

Why Central Nervous System
Numerous studies have substantiated the contribution of genetic factors to psychiatric and central nervous system disorders and the pace of discovery of biomarkers to guide treatment for these disorders is accelerating. PGxHealth has been at the forefront of this research with its programs to develop genetic tests that can be used to predict the effectiveness and safety of drugs for the treatment of depression and schizophrenia.

Depression
Marker Discovery Example: Vilazodone

In 2003, about 18.8 million American adults suffered from depressive illness. However, since only one-half to two-thirds of patients who require treatment for their depression respond to the current first-line treatment option, Selective Serotonin Reuptake Inhibitors (SSRIs), many are forced to try more than one medication before they experience relief from their symptoms. Typically, patients with these disorders must be treated for weeks to months before their symptoms are meaningfully reduced. During this time, patients and their families suffer the consequences of uncontrolled disease, which may include lost time from work, unwanted side effects of the therapeutic, drug-drug interactions and lack of compliance due to poor or no response. All of these undesirable effects result in increased cost of care and burden to the healthcare system.

By targeting therapy based on genetics, the likelihood of response can be increased. Thus, the right drug will be prescribed the first time, giving patients and their care givers increased confidence that a positive response will be achieved. This should result in increased compliance, less switching, improved physician and patient satisfaction and decreased cost of care.

Clinical Data acquired world-wide exclusive rights to develop and market vilazodone from Merck KGaA. This compound has a novel dual mechanism of action, acting as both a potent selective serotonin-reuptake inhibition (SSRI) and as a 5-HT1A partial agonist, suggesting it may be more effective than currently available SSRIs. Clinical Data initiated the first of 2 pivotal trials for vilazodone in February 2006 in which genetic biomarkers for response to vilazodone will be identified. We anticipate an NDA Filing by end of year 2008.

Vilazodone is being developed as a targeted antidepressant. The drug will be targeted through use of a genetic test that is being developed in parallel with the pivotal trials. This test will be able to predict if a patient is likely to respond to vilazodone. Physicians believe that this strategy will both improve compliance and increase response rates, which will result in decreased cost of care. This will position vilazodone as a unique product in the treatment of depression, a product that can be targeted to an individual patient’s needs. To find out more about vilazodone, please click here.

Schizophrenia
Biomarker Discovery Example: Clozapine

Schizophrenia is a devastating disease afflicting 1% of the population across varied geographical regions of origin. Characterized by delusional beliefs, auditory hallucinations, disorganized thought patterns and apathy, schizophrenia is a chronic disorder that begins in early adulthood. The social and financial implications of schizophrenia are high. Patients withdraw socially, have difficulty sustaining relationships and are often unable to work. The cost of this loss of productivity combined with the burden of medical care is estimated to be $32.5 billion per year in the United States alone.

Clozapine is the only drug used to treat schizophrenia that has been proven to have superior efficacy to conventional neuroleptics in treatment refractory patients and has been demonstrated to reduce the risk of suicide in patients with schizophrenia. However, its use is limited, in part due to the side effect of agranulocytosis experienced in a small percentage of the population, an immune compromising condition that may lead to death. Treatment with clozapine requires the maintenance of patient registries to monitor for a reduction in the white blood count (WBC) and absolute neutrophil count (ANC) and to protect patients who are susceptible to clozapine induced agranulocytosis (CIA) from re-treatment with the drug. Under this “no blood, no drug” policy, patients are required to submit to frequent blood monitoring for the duration of their treatment with clozapine, which may be for many years. These procedures are not only uncomfortable and costly, but are burdensome to many patients, can lead to fibrosed veins over the course of many years of therapy, and may adversely affect patient compliance. This severe side effect, although occurring in only a very small percentage of patients, encumbers an otherwise effective drug with an expensive distribution system that limits use by consumers who suffer from a chronic debilitating illness. For this reason, the decision to start clozapine is a difficult one for many patients and their families. In addition, patients who are already treated with clozapine may be facing the decision whether to continue treatment in the face of falling white blood cell counts.

PGxHealth has completed the first part of a program to discover genetic markers that will identify patients at lower risk for clozapine-induced agranulocytosis. Clinical Data’s genetic test will give physicians, patients and their families new information about each patient’s risk for CIA and lead to a more informed decision about beginning or continuing treatment with clozapine. Further development of such a test has the potential of safely increasing the use of this highly efficacious drug by improving patient compliance, increasing prescriptions, and possibly leading to reduced frequency of blood monitoring in a subset of patients. Clinical Data and its PGxHealth division will work with the US FDA, physicians, testing laboratories, and patients to demonstrate the ability of its genetic test to predict patients who can safely forego blood monitoring with continued clozapine treatment. To find out more about clozapine, please click our e-mail link info@PGxHealth.com.