Development of a Personalized Medicine Interface for the Safe and Effective Treat

DESCRIPTION (provided by applicant): Improvements in the safety and efficacy of warfarin therapy will result from intelligent application of knowledge derived from inherited characteristics (CYP2C9 and VKORC1) of individual patients, only when this knowledge is applied through a standardized interventional approach. The fundamental pharmacologic influences of CYP2C9 and VKORC1 have been unequivocally established and validated by numerous academic reports including those conducted by PGXL and its affiliated thought leaders. There is a clear cause and effect relationship between inherited variation in these enzymes and complications in warfarin management. Delayed metabolic clearance of S-warfarin (CYP2C9) and a lower concentration threshold for response (VKORC1) have a profound effect on the clinical pharmacology of warfarin and defeat the utility of standard dosing and monitoring practices. Current warfarin dosing practices, which rely on standardized initiation dosing and INR-based dose adjustments, are fundamentally flawed when applied to patients without regard to their unique metabolic and response characteristics. PGXL has developed a personalized medicine interface (PerMIT) which provides interpretive, genotype-based guidance to facilitate appropriate clinical practice modifications accommodating patient individuality. PerMIT:Warfarin is the first HIPAA-compliant and secure pharmacogenetics-based interventional methodology for warfarin anticoagulation management. PerMIT:Warfarin applies fundamental pharmacologic influences of inherited patient characteristics to individually tailor warfarin therapy. The mathematical operations that form the basis of PerMIT have been validated for accuracy, and PGXL is now prepared for prospective interventional trials. PGXL Laboratories has engaged all of the key external resources necessary to construct a comprehensive strategic framework to gather compelling clinical evidence of improved outcomes and to move PerMIT:Warfarin through the regulatory and commercialization processes. This SBIR Phase II Competitive Renewal application is designed to achieve the regulatory compliance and medical evidentiary standards set forth by federal regulatory bodies and the demands of the marketplace. PUBLIC HEALTH RELEVANCE: Individualised therapeutic management based on pharmacogenetic information requires a standardized interventional approach. PerMIT:Warfarin is the first pharmacogenetics-based interventional methodology for warfarin anticoagulation management. PerMIT:Warfarin is a Class II device under FDA classification regulation 21 CFR 864.7750. The Center for Medicare and Medicaid Services (CMS) has established a standard for warfarin pharmacogenetics reimbursement, calling for multi-site randomized controlled trials to assess the benefit of pharmacogenetics to warfarin therapeutic management. This SBIR Phase II Competitive Renewal application is designed to achieve the regulatory compliance and medical evidentiary standards set forth by these regulatory bodies.