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The Invader® UGT1A1 Molecular
Assay Workflow

for In Vitro Diagnostic Use

Confidence

  • 100% accurate as compared to bi-directional sequencing of 285 clinical samples.4
  • 98% reproducibility in a multi-center clinical study.4

Convenience

  • Minimal Hands-On Time (<2 hours, including DNA isolation).

Background

  • UDP-glucuronosyltransferase 1A1 (UGT1A1) is a polymorphic enzyme responsible for the metabolism of endogenous compounds and drugs, including the chemotherapeutic agent irinotecan (trade name CAMPTOSAR®).1,2
  • The most common polymorphism is a variation in the number of TA repeats in the TATA box region of the UGT1A1 gene. The presence of seven TA repeats (UGT1A1*28) instead of the normal six TA repeats (UGT1A1*1) reduces gene expression and results in impaired metabolism. This variant allele is common in many populations, and occurs in 38.7% of Caucasians, 16% of Asians and 42.6% of Africans.1,2
  • Studies have shown that impaired metabolism in patients who are homozygous for the UGT1A1*28 allele results in severe, dose-limiting toxicity during irinotecan therapy. These findings led to a recent update in the irinotecan label to include dosing recommendations based on the presence of a UGT1A1*28 allele.3
  • Individuals with the UGT1A1*28 allele may require dose modifications for other drugs that are metabolized by the UGT1A1 enzyme.

The Invader® UGT1A1 Molecular Assay

  • First IVD pharmacogenetic test using the patented Invader® Chemistry.
  • Determines UGT1A1*28 genotype as recommended in the recent label update for the chemotherapeutic irinotecan, which is approved as first-line therapy for metastatic colorectal cancer.
  • Identifies patients at risk for severe toxicity when treated with irinotecan therapy.
  • Studies ongoing to determine clinical utility for UGT1A1*28 genotyping for new and existing drugs metabolized by UDP glucuronosyltransferase.
Patient Group Assay Result Prevalence Risk of Neutropenia
All Patients No Test - - - 10 in 100
Wildtype *1/*1 Genotype 6/6 50% 0 in 100
Heterozygous-deficient *1/*28 Genotype 6/7 40% 12 in 100
Heterozygous-deficient *28/*28 Genotype 7/7 10% 50 in 100
Invader Reagents

References

  1. Innocenti F, Undevia SD, Iyer L, Chen PX, Das S, Kocherginsky M, Karrison T, Janisch L, Ramirez J, Rudin CM, Vokes EE, Ratain MJ. Genetic variants in the UDP-glucuronasyltransferase 1A1 gene predict the risk of severe neutropenia of irinotecan. J Clin Oncol 2004; 22(8); 1382-1388.
  2. Beutler E, Gelbart T, Demina A. Racial variability in the UDP-glucuronosyltransferase 1 (UGT1A1) promoter: a balanced polymorphism for regulation of bilirubin metabolism? Proc Natl Acad Sci U S A 1998;95:8170-4.
  3. http://www.pfizeroncology.com/hcp/camptosar.aspx
  4. The Invader® UGT1A1 molecular assay 510k summary (K051824) (For detailed instructions and equipment specifications, please see the Invader® UGT1A1 Molecular Assay package insert.)
  5. Camptosar® is a registered trademark of Pfizer Corporation.
  6. Invader® is a registered trademark of Third Wave Technologies, Inc. All rights reserved. The Invader® chemistry is protected by foreign and domestic patents. ©2007 Third Wave Technologies, Inc.

The Invader® chemistry is protected by foreign and domestic patents.