Roche's AmpliChip CYP450 test receives FDA clearance

First microarray-based diagnostic test for detection of genetic variations that can influence drug efficacy and adverse drug reactions

18 January 2005

Roche announced that its first microarray-based test, the AmpliChip CYP450 Test, has been cleared by the US Food and Drug Administration (FDA) for diagnostic use in the United States. This test, which is powered by Affymetrix microarray technology, analyses a patient’s Cytochrome P450 2D6 and 2C19 genotypes from genomic DNA extracted from a blood sample. Test results will allow physicians to consider unique genetic information from patients in selecting medications and doses of medications for a wide variety of common conditions such as cardiac diseases, pain and cancer.

Heino von Prondzynski, CEO Division Roche Diagnostics and Member of the Roche Executive Committee, said: "This new test allows physicians access to information that could help to prevent harmful drug interactions and to assure drugs are used optimally. Adverse drug reactions cause a huge number of hospitalizations in the US. Our new test also will, in some cases, enable patients to avoid suboptimal or even harmful treatment choices. For patients it is extremely important to know whether pain killers or anaesthetics might work differently or not at all for them. Poor or slow metabolizers may experience much longer lasting effects of the treatment. The knowledge of the reasons behind this will empower people to ask for different and better-to-tolerate medicines. The use of this test is an important step forward in making personalized medicine a reality and has the potential to help physicians improve patient outcomes."

Two key genetic regions encoding the enzymes of the cytochrome P450 complex are the established as the 'gold standard' of molecular diagnostics worldwide. The knowledge Roche Diagnostics has acquired in the past 18 years is protected by several hundred patents.

The multiple variations in the CYP2D6 gene can result in poor, intermediate, extensive ("normal"), or ultra-rapid metabolism of CYP2D6-dependent drugs from a variety of classes, including anti-depressants, anti-psychotics, anti-arrhythmics, beta-blockers, pain medications, anti-emetics, and some anti-cancer drugs. Variations in the CYP2C19 gene result in either normal or poor metabolism of CYP2C19-dependent drugs from a variety of classes, including anti-convulsants, proton pump inhibitors, benzodiazepines, and anti-malarials.

Poor metabolizers treated with drugs that are dependent on 'normal' enzyme activity are at increased risk for excessive or prolonged levels of the drug in their blood (excessive or prolonged therapeutic effect or toxicity), while ultra-rapid metabolizers may not achieve sufficient therapeutic levels in their blood with standard dosing. In the case of pro-drugs (that is, drugs that require enzymatic action before they become the therapeutic compound in the body), the opposite phenomenon occurs. It is important to note that multiple drugs taken at the same time (concurrent medications) and many other environmental factors such as diet, gender, and overall health, can inhibit or induce Cytochrome P450 enzyme activity.

The AmpliChip CYP450 Test was launched in Europe in the autumn of 2004. The test combines the strengths of two industry gold-standards, Roche’s patented polymerase chain reaction (PCR) amplification technology, which replicates even minute amounts of genetic material to detectable levels, and Affymetrix high-density microarray technology on glass chips no bigger than a thumbnail arrayed with tens of thousands of precisely arranged DNA fragments.

Affymetrix, Inc. announced on December 23rd, 2004 that its GeneChip System 3000Dx instrumentation, on which the AmpliChip CYP450 Test is run, has also received FDA clearance for diagnostic use in the United States.



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