Skip to main content
Premium Trial:

Request an Annual Quote

MDx/CDx Focus: Cepheid Updates BCR-ABL Test; Medicare Covers Transgenomic Plavix Dx; Lungevity Awards


Cepheid Launches Standardized Xpert BCR-ABL Monitor Test

Cepheid has released an updated version of its Xpert BCR-ABL Monitor test, which now incorporates "lot-specific standardization" based on World Health Organization BCR-ABL guidelines.

Xpert BCR-ABL Monitor has CE-IVD marking in Europe and runs on Cepheid's GeneXpert system. According to the company, the test can detect BCR-ABL mRNA transcripts in the peripheral blood of chronic myelogenous leukemia patients in about two hours.

Two years ago, Cepheid and Novartis announced they were collaborating on the development of a test for monitoring BCR-ABL gene transcripts to help doctors more reliably manage Philadelphia chromosome-positive CML patients treated with Novartis' oncologic Gleevec and other tyrosine kinase inhibitors (PGx Reporter 10/13/2010). The companies have said they plan to file for regulatory approval for the test through the US Food and Drug Administration.

"The new lot-specific standardization translates to even greater clinical accuracy for physicians as they compare BCR-ABL values over time within the same patient, as well as comparability across geographic locations where testing is being performed," Cepheid CEO John Bishop said in a statement.

Gleevec has been on the market for more than a decade for the treatment of Ph-positive CML, and among oncologists it is already standard practice to monitor BCR-ABL transcript levels to confirm patients have the disease and to ensure patients aren't relapsing or having a refractory response to treatment. There is a lack of standardized procedures and reference materials in leukemia monitoring, however, which can make it difficult to compare results obtained from different labs.

The WHO-specific lot-to-lot standardization of the updated BCR-ABL monitoring test will allow healthcare providers to compare mRNA transcripts in CML patients' blood between labs, according to a Cepheid statement.

Novartis, in collaborating with Cepheid in this effort, is hoping to reduce variability in BCR-ABL transcript monitoring by developing and commercializing a test that reports results in line with a standard called the International Scale. Published by the European LeukemiaNet consortium, the International Scale was developed with numerous stakeholders at the National Institutes of Health to serve as a global standard for detecting and reporting BCR-ABL transcript levels.

CML is a cancer of the white blood cells caused by an unregulated growth of myeloid cells. A translocation of chromosomes 9 and 22 results in the BCR-ABL fusion gene that drives proliferation of myeloid cells in the bone marrow and in the blood. Since BCR-ABL monitoring is used to assess whether CML patients are responding to treatment, standardized testing methods could help doctors more reliably manage patients receiving tyrosine kinase inhibitors such as Gleevec, Novartis' Tasignia, and Bristol-Myers Squibb's Sprycel.

With the introduction of TKIs, "CML has been transformed into a chronic condition with a good long-term prognosis," Cepheid said in a statement. "The goal of treatment is to reach a major molecular response, defined as a 3 log reduction (

"In order to accurately assess treatment response, it is essential that variability in testing methodologies be tightly controlled," the company added.

Cepheid's Bishop also said in a statement that in addition to this latest update to its BCR-ABL monitoring test, the company is planning to roll out a number of molecular diagnostics on its GeneXpert platform.

Medicare Contractor Agrees to Cover Transgenomic's Clopidogrel Genetic Absorption Activation Panel

Transgenomic this week announced that Medicare contractor National Government Services has agreed to cover its Clopidogrel Genetic Absorption Activation Panel.

“Medicare is the largest US payor and currently covers approximately 75 percent of the patients for whom the C-GAAP test would be ordered," Transgenomic CEO Craig Tuttle said in a statement.

C-GAAP is a saliva-based test that identifies patients with variations in the CYP2C19 and ABCB1 genes associated with response to the anti-platelet drug clopidogrel. As a brand name drug, clopidogrel was marketed by Bristol-Myers Squibb and Sanofi Avenits as Plavix; it went off patent earlier this year.

While clopidogrel's label recommends testing for loss-of-function variants in the CYP2C19 gene to assess which patients may not respond to the drug, inclusion of SNPs in the ABCB1 gene is unique to Transgenomic’s panel. The company stated it has issued and pending patents on ABCB1 gene variations.

According to the company's estimates, there are approximately six million new patients prescribed clopidogrel annually, and half of this population harbors variations in the CYP2C19 and ABCB1 genes. "Patients with dysfunctional CYP2C19 and ABCB1 genes treated with clopidogrel exhibit a 50 percent increase in major adverse cardiovascular event rates than do patients with normal CYP2C19 and ABCB1 genetic function," the company said in a statement.

Transgenomic is marketing the test as a tool that doctors can use in concert with patients' clinical information to choose the treatment they are most likely to benefit from. Although the test is intended to guide treatment decisions for a specific drug, clopidogrel, the company has not yet sought clearance from the US Food and Drug Administration for this test. The FDA has indicated that tests that claim to select which patients should receive a specific treatment need to be approved or cleared by the agency.

Transgenomic launched C-GAAP in November last year as a lab-developed test. Formerly called PGxPREDICT:Clopidogrel, C-GAAP came under Transgenomic's pipeline with the firm's 2010 acquisition of Clinical Data's diagnostics business (PGx Reporter 12/1/2010).

Last year, the FDA rejected premarket approval for Nanosphere's Verigene CYP2C19 Plavix Metabolism Test and asked the firm to provide additional data before it would review the test. In 2010, the FDA granted 510(k) clearance to AutoGenomics' Infinity CYP2C19 Assay, but based on the data submitted as part of the application the company cannot market the assay as a pharmacogenetic test to predict which patients will likely respond to Plavix (PGx Reporter 6/22/2011; 10/27/2010).

According to industry players, adoption of genomic testing to guide clopidogrel administration has been hindered by conflicting meta-analysis on the association of CYP2C19 loss-of-function markers and reduced drug response. Meanwhile, Transgenomic is likely hoping that Medicare coverage and the ABCB1 variations in its test will give it a leg up over competitors.

It is unknown whether Transgenomic is planning to or has submitted an application with the FDA to garner marketing approval for C-GAAP. The company did not respond to questions from PGx Reporter.

Lungevity Awards $1.5M to Molecularly Guided Lung Cancer Research

Lung cancer advocacy group Lungevity Foundation has awarded $1.5 million in grants to researchers investigating molecularly guided strategies for early lung cancer detection and personalizing treatments.

Recipients of the organization's Career Development Awards for Translational Research include Jennifer Beane of Boston University ("Biomarkers of Pre-malignant Disease Progression for Lung Cancer Detection"); Lauren Byers of University of Texas MD Anderson Cancer Center ("PARP1 as a Novel Therapeutic Target in Small Cell Lung Cancer"); Mohamed Hassanein of Vanderbilt University Medical Center ("Developing New Non-invasive Methods for the Diagnosis of Lung Cancer"); Christopher Maher of Washington University, St. Louis ("Molecular Predictors of Outcome in Non-small Cell Lung Cancer"); and Viswam Nair of Stanford University ("In-vivo and In-vitro Diagnostics to Improve Lung Cancer Care").

The grant recipients will get $100,000 per year for up to three years, participate in a mentoring program at their institutions, and become ex officio members of Lungevity's Scientific Advisory Board for the duration of the award.

Lungevity's Career Development Awards for Translational Research aim to "identify a cohort of future research leaders who will keep the field of lung cancer research vibrant with new ideas," the group said in a statement announcing the grants. The award program is supported by Genentech, a drug developer that is significantly invested in advancing personalized medicine strategies in cancer.

Genentech is currently planning to expand the indication of its drug Tarceva in non-small cell lung cancer patients who harbor EGFR mutations in their tumors. Last year, the European Commission approved the use of Tarceva as a first-line treatment for NSCLC in patients with EGFR mutations (PGx Reporter 9/7/2012) and last month, the UK's National Institute for Health and Clinical Excellence issued a draft guidance recommending that the country's National Health Service pay for Tarceva as an option for this patient population. The company is in discussions with the US Food and Drug Administration about launching Tarceva in this population (PGx Reporter 06/08/2011).

In addition to the Career Development Awards for Translational Research, Lungevity and its partners are providing $2 million for ongoing lung cancer research projects, many of which are exploring molecularly driven strategies for the early detection of lung cancer. Recipients of these second-year research grants include: Jeffrey Borgia of Rush University Medical Center for "Autoantibody-based Biomarkers to Aid in the Early Diagnosis of Lung Cancer;" York Miller of University of Colorado Denver for "Biomarkers to Improve Clinical Assessment of Indeterminate Lung Nodules;" Suzanne Miyamoto of the University of California-Davis for "A System Biology Approach to Biomarkers for Early Detection of Lung Cancer; and Edward Patz of Duke University Medical Center for "Serum Biomarkers for the Early Detection of Lung Cancer."

Lungevity is also awarding second-year funding to advance research on targeted treatments for lung cancer. The grant recipients are: David Carbone of Vanderbilt University Medical Center for "Biomarkers for Personalizing Adjuvant Therapy in NSCLC - Increasing Cures;" Edward Gabrielson of Johns Hopkins University School of Medicine for "Examining LKB1 Status as a Biomarker for Response of Lung Cancer to Metformin;" Rebecca Heist of Massachusetts General Hospital for "Identifying Tumor Genomic Changes in Lung Cancers;" John Heymach of University of Texas MD Anderson Cancer Center for "Predictive Blood-based Markers of Response to VEGF Inhibitors in NSCLC;" and Alexander Steven Whitehead of University of Pennsylvania for "Folate-related Biomarkers as Predictors of Response to Pemetrexed Therapy."

According to Lungevity, approximately 226,000 people will be diagnosed with lung cancer in the US this year and 84 percent of these patients will die less than five years after their diagnosis. The foundation's 17-member scientific advisory board decides which lung cancer research projects to award grants to.