Co-development of CDx
Companion Diagnostics
Companion Diagnostics or theranostics is the term used to describe the proposed process of systematically reviewing patient's individual medical and or genetic profile to develop preventative or therapeutic care specific to that patient's genetic makeup and the relationship to a given drug. A key attribute to this model is the ability to utilize molecular assays to measure specific genes, proteins or other biomarkers to help identify and individual's ability to potential respond to a specific drug and or to tailor the dose of a drug to a patient's individual profile.
The theranostics opportunity arises by applying methylation detection to different predictive oncology questions both “classic” genotoxic1 chemotherapy and “modern” targeted therapies2. The opportunity to improve therapeutic treatments is significant especially in oncology as indicated in table I. On average, oncology therapeutics have efficacy rates of approximately 25%. The consequences of low response rates are enormous in terms of quality of life and cost of care, forcing patients to seek additional treatment options and contend with medical bills from ineffective treatments. The successful application of methylation-based theranostic markers would have a significant impact on improving treatments outcomes in the field of oncology.
Predictive assays predict which drug or treatment regimen is likely to be most effective for a specific patient by analyzing the molecular make-up of the individual patient’s tumor. The goal of pharmaco Dx tests is to provide information to the physician for a rational optimization of each patient’s drug therapy. Along these lines, MDxHealth is developing a similar Pharmaco Diagnostics molecular diagnostic test for use with a Merck/Schering-Plough alkylating agent drug temozolomide, initially for brain cancer.
MDxHealth has discovered new biomarkers for therapy response and resistance, and is in the process of developing these Pharmaco Dx products together with pharmaceutical and biotechnology companies.
The anticipated success of personalized medicine depends largely on a molecular-targeted drug having a linked or ‘’companion’’ diagnostic test designed to determine precisely whether a patient will benefit from the specific treatment. There are two main groups of companion diagnostics:
- Tests that have been developed after a drug has come to market
- Tests that are being developed in conjunction or as a companion to the drug (co-development)
There is an increasing number of diagnostic (Dx) tests that are paired to therapeutic (Rx) drugs. Patient advantages include: improving median survival and overall response rates to chemotherapy. For Pharma advantages include: fast-track approval with the FDA based on the test/drug combination data proving that studying a subset of responders based on a theranostics can shorten the drug development and approval times. Regulatory agencies like the U.S. Food and Drug Administration (FDA) and the European Medicines Agency ( EMA) are encouraging the use of biomarkers (theranostics) in informing prescribing decisions. The FDA and EMA have recently recommended that biomarker testing be performed during clinical trial evaluations. Several products are currently approved to be used as a medical assessment tool prior to prescribing certain drugs.
As a result, pharmaceutical companies increasingly rely on companion diagnostics to stratify patients for clinical trials (ie. select those patients in whom the drug under investigation would be most effective). This allows companies to conduct clinical trials faster and with smaller patient cohorts. In addition, regulatory authorities are starting to require pharmaceutical companies to integrate companion diagnostics, particularly in connection with targeted therapies, to ensure safety and efficacy, and control costs.
Brain Cancer product
Predict MDx for Brain, MDxHealth’s most advanced personalized treatment product is a test for predicting patient response to alkylating agents, a class of chemotherapy drugs. The test assesses the methylation status of the MGMT gene, which is correlated with response to drug therapy. The MGMT gene is a crucial DNA repair gene. MDxHealth’s MGMT assay determines the methylation status of the MGMT gene in tumor tissue, and can be used as a predictive assay for the treatment of brain cancer.
The MDxHealth MGMT gene test has been shown on thousands of patients to be able to distinguish which cancer patients are likely to respond to the most commonly used class of brain cancer drugs called alkylating agents. This patented methylated gene test is attractive for new brain cancer drug developers since they can more easily target their new drugs to the patients who usually do not respond to the traditional alkylating agent drug regime.
For further information see also:
Colon cancer product
PredictMDx for Colon Cancer is a molecular test which provides physicians with predictive information. This information, in conjunction with traditional risk factors, provides physicians valuable information on the likelihood that a patient will benefit from the use of Irinotecan based chemotherapy cocktails, allowing an informed decision between Oxaliplatin and Irinotecan based treatment courses.
About 20% of colon cancer patients are diagnosed with metastatic, stage IV disease. Stage IV colon cancer is usually treated with chemotherapy cocktails containing either Oxaliplatin (FOLFOX) or Irinotecan (FOLFIRI). These two regimens have similar efficacy, but have different toxicity profiles. There is a need for biomarkers that predict to which therapy regimen the patient will respond and that help reduce needless toxicity.
For further information see also: