October 15, 2008 (Vol. 28, No. 18)

Genomas Seeks to Improve the Use of Drugs Already on the Market

A recent review in the Journal of the American Medical Association concluded that genomic medicine should be part of the risk assessment and treatment of common chronic diseases, yet knowledge about genomic medicine is not being integrated into clinical practice.

Gualberto Ruano, M.D., Ph.D., an internist and geneticist, is striving to bring personalized medicine to the clinic. He founded Genomas in 2004 to discover biomarkers to identify patients who are susceptible to known side effects of common drugs. “We are a healthcare-delivery company developing a biomarker platform to improve the use of drugs already on the market,” says Dr. Ruano, president and CEO.

The firm’s technology, called PhyzioType™ systems, is a DNA-guided platform aimed at personalizing drug delivery. PhyzioType Clinical Management Systems consist of an ensemble of inherited DNA markers genotyped by arrays and interpreted by biomathematical algorithms to advise physicians about drug treatments for individual patients.

“Today’s medications do their job, but side effects that disable patients and require a lot of clinical time are common. If we could prevent common side effects everybody would win, including patients, the healthcare system, and pharmaceutical companies,” adds Dr. Ruano.

The PhyzioType technology, which the FDA classifies as a medical device, is in the research-and-development stage. Genomas plans to submit its biomarker platform for FDA approval by 2009. Each PhyzioType system requires about 20 biomarkers or SNPs to predict the side effects of a drug. Patents are pending on some ensembles of biomarkers and bioinformatic methods for interpreting the genotypes and calculating risks.

When approved, Genomas will sell biomarker kits, hardware, and software to clinical laboratories. Physicians will use the information to guide their decisions about the likelihood of side effects occurring in individual patients. “Our markets are patients, hospitals, and doctors,” says Dr. Ruano.

Genomas operates a prototype genotyping service at Hartford Hospital, where clinical laboratories test patients for potential side effects from antidepressants and warfarin. When the FDA approves PhyzioType systems, national expansion will begin through reference laboratories, diagnostic companies, and healthcare networks.

PhyzioType Systems in Development

Genomas focuses on finding biomarkers for medications prescribed to treat cardiovascular disease, psychiatric illnesses, and diabetes. Because a large sector of the population takes drugs for these disorders, “there’s a substantial need to improve the precision of treatments in these areas,” Dr. Ruano explains.

Most advanced is the PIMS PhyzioType system to prevent psychotropic-induced metabolic symptoms associated with atypical antipsychotic drugs. Up to one-third of patients who take drugs such as Risperdal® (resperidone) and Zyprexa® (olanzapine) experience drug-induced prediabetic metabolic symptoms like weight gain and increases in blood lipid levels. “We can predict, based on PhyzioTypes, who is susceptible to these side effects,” says Dr. Ruano.

In the May 2007 issue of Molecular Psychiatry, Dr. Ruano and colleagues at the University of Kentucky Mental Health Research Center showed that resperidone and olanzapine target different metabolic pathways. Olanzapine induces a series of SNPs coding for apolipoproteins E and A4, which are associated with weight gain.

A different series of SNPs coding for leptin receptor and a neuropeptide Y receptor are associated with weight gain in resperidone-treated patients. “We can even differentiate between medications of the same type to give safety guidance,” Dr. Ruano insists.

The SINM PhyzioType system targets statin-induced neuromyopathy, a side effect of statin drugs. About 15% of patients experience disabling side effects from statin drugs including muscle aches, cramps, weakness, and muscle injury. In March, Genomas received a $1.2 million Fast-Track Phase I-II SBIR grant from the NIH to find biomarkers to predict an individual’s risk of statin-induced neuromyopathy.

The GLIM PhyzioType system looks at glucose and insulin modulators used for managing diabetes. The oral thiazolidinedione drugs Actos® and Avandia® are used to lower insulin resistance. But in one-fifth of patients the drugs cause weight gain, edema, and fat accumulation, which worsen diabetes symptoms and lead to heart failure. “We have the technology to predict which patients will have problems,” Dr. Ruano reports.

To improve the accuracy of its personalized medicine platform, Genomas established a new program at the University of Puerto Rico Medical Sciences Campus. The population of Puerto Rico is highly genetically diverse due to its history, making it a good place to develop DNA-guided systems for clinical management. “It allows us to check our algorithms to see how they work in a heterogeneous population,” says Dr. Ruano.

The first program will focus on warfarin dosing. The observational data collected in Puerto Rico will make the bioinformatic models more accurate. “If you are developing rules for DNA-guided treatment, the best place to improve them is in a place where the population is heterogeneous,” says Dr. Ruano. Eventually, the information will be incorporated into evidence-based medicine to impact the practice of internal medicine. Doctors will use the decision-making rules to prescribe drugs.

The business model at Genomas calls for using biomarkers to improve the prescribing of drugs already on the market. The company does not plan to use the biomarker data that it collects to develop new drugs of its own. Clues about new drug targets, however, gleaned from the technology platform could be licensed to others who are in the drug development business.

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