Additional thoughts on warfarin, genetic testing and personalized medicine courtesy of Dr Caroline Wright of the Foundation for Genomics and Population Health (a charitable company registered in England and Wales) …
“Just a month after the label for the blood-thinning drug warfarin was updated to explain that genetic variation in specific genes influences how patients respond to the drug (see previous news article), the US Food and Drug Agency (FDA) has approved the first genetic test for warfarin sensitivity.
Warfarin is the most widely used anti-coagulant medication in the world, prescribed to over 2 million people a year to prevent blood clots, heart attacks and strokes. Patients can display markedly different responses to the drug, so doses vary enormously between individuals. Achieving the correct dose is critical, as patients who receive too high a dose are at risk of severe bleeding, whilst those who receive too low a dose may remain at risk of life-threatening blood clots.
The Nanosphere Verigene Metabolism Nucleic Acids Test detects particular variations in two genes, CYP2C9 and VKORC1, which are involved in the metabolism and mechanism of action of warfarin respectively. Specific variants of these genes are identified from a patient sample by hybridization to sequence specific probes (oligonucleotides) attached to a microarray. These are subsequently detected using the Verigene System which measures light scattering from gold nanospheres tethered to another complementary oligonucleotide. Depending upon the genotype, patients can then divided into slow, fast or normal warfarin metabolisers and their doses adjusted accordingly.
FDA states that it cleared the test based on a broad range of published literature together with the results of a study, conducted by the manufacturer, on hundreds of DNA samples. ‘In a three site study, the test was accurate in all cases where the test yielded a result, although 8% of the tests could not identify which genetic variants were present.’ Although the Nanosphere test is not intended as a stand-alone tool to determine optimum drug dosage but to be used alongside clinical evaluation and other tools to determine the best treatment for patients, this approval underlines the FDA’s ongoing commitment to personalised medicineâ€
Remember – PDUFA page 182. Working together we can accomplish great things for the public health.
“Just a month after the label for the blood-thinning drug warfarin was updated to explain that genetic variation in specific genes influences how patients respond to the drug (see previous news article), the US Food and Drug Agency (FDA) has approved the first genetic test for warfarin sensitivity.
Warfarin is the most widely used anti-coagulant medication in the world, prescribed to over 2 million people a year to prevent blood clots, heart attacks and strokes. Patients can display markedly different responses to the drug, so doses vary enormously between individuals. Achieving the correct dose is critical, as patients who receive too high a dose are at risk of severe bleeding, whilst those who receive too low a dose may remain at risk of life-threatening blood clots.
The Nanosphere Verigene Metabolism Nucleic Acids Test detects particular variations in two genes, CYP2C9 and VKORC1, which are involved in the metabolism and mechanism of action of warfarin respectively. Specific variants of these genes are identified from a patient sample by hybridization to sequence specific probes (oligonucleotides) attached to a microarray. These are subsequently detected using the Verigene System which measures light scattering from gold nanospheres tethered to another complementary oligonucleotide. Depending upon the genotype, patients can then divided into slow, fast or normal warfarin metabolisers and their doses adjusted accordingly.
FDA states that it cleared the test based on a broad range of published literature together with the results of a study, conducted by the manufacturer, on hundreds of DNA samples. ‘In a three site study, the test was accurate in all cases where the test yielded a result, although 8% of the tests could not identify which genetic variants were present.’ Although the Nanosphere test is not intended as a stand-alone tool to determine optimum drug dosage but to be used alongside clinical evaluation and other tools to determine the best treatment for patients, this approval underlines the FDA’s ongoing commitment to personalised medicineâ€
Remember – PDUFA page 182. Working together we can accomplish great things for the public health.
