AlloMap molecular expression testing

Pierre Cassigneul, CEO of XDx, on the impact the Human Genome Project had on his company.

Patients who have had a heart transplant have been through illness, fear, and trauma that most us will never know. For most patients, their new heart gives them a renewed lease on life. However, to ensure that their immune systems are not rejecting their heart, they must submit to dozens of endomyocardial biopsies, an invasive procedure that takes pieces of heart tissue, in the years following their transplant. The biopsy procedures are uncomfortable, sometimes painful, and while uncommon, the procedure can generate side effects that are occasionally serious. Further, multiple studies show a considerable amount of variability in biopsy interpretation among pathologists, who examine the samples for visual evidence of cellular rejection.

Because of these issues, there was a critical need for a noninvasive test that had a high level of confidence and reproducibility in assessing acute cellular rejection. AlloMap molecular expression testing is proving to be that test. Using a blood sample rather than heart tissue, the AlloMap test examines activity in the genes of the immune system, and helps physicians determine a patient’s rejection status.

Technologies developed during the Human Genome Project (HGP) helped lead to the development of AlloMap molecular expression testing, the first and only noninvasive test that rules out rejection in patients with a heart transplant. The HGP was an international 13-year effort culminating with the complete sequence of the human genome being deciphered and made available to medical researchers in a wide variety of fields.

AlloMap testing was developed over four years through a multi-center study in which eight of the leading heart transplant centers participated. During the study, over 5000 blood samples were compared to an equal number of biopsy samples from nearly 800 patients. Using the blood samples, over 7,000 blood-related genes (out of the 30,000 genes in the genome) were identified as potential candidates for determining acute cellular rejection. The study winnowed out all but the best genes for the job, taking into consideration gene stability and other factors that increased reproducibility and performance of the test. In the end, 20 genes were selected for the AlloMap test, and a sophisticated algorithm was developed that converts the individual gene activity readings into a single score for use by the physician. The test has been available commercially in the US for over two years and is growing in use, with about one third of all heart transplant centers using the test.

How does AlloMap testing compare in cost to heart biopsy? The list price for AlloMap testing is $2,950 while biopsy costs payers between $3,000 and $4,000 on average. But the primary advantage of the AlloMap test is the objective, quantitative and reproducible result. obtained without the discomfort and risks associated with the endomyocardial biopsy.

The quantitative performance and reproducibility of the AlloMap test enable the physician to monitor patients longitudinally by comparing changes from one test result to another. This approach allows for individualized patient management based on each patient’s immune response. This test and others that may follow from the work at XDx are providing a basis for personalized medicine.

With research and development projects underway for lung transplant patients and lupus patients, the common thread in XDx’s ongoing work is the identification of specific immune and inflammatory processes from blood samples before significant organ damage occurs. This research will lead to a better understanding of diseases and disorders of the immune system. Further, as this understanding of diseases at the molecular level increases, it may allow pharmaceutical companies to develop improved, targeted therapies for critical disease mechanisms. Other possible outcomes of this development work are tests that correlate with drug efficacy, enabling clinicians to optimize the therapeutic regimen for each patient by maximizing therapeutic efficacy while minimizing undesirable side effects. Patients will reap the benefits as gene expression technology is widely adopted.

Key points:

• Gene expression technology provides a noninvasive, objective, reproducible and specific test for ruling out heart transplant rejection
• The same technology is likely to be applicable to assessing the rejection process of other solid organs, as well as autoimmune diseases
• These tests provide a basis for personalized medicine and may lead to new developments in therapeutics specific to the disease state

Pierre Cassigneul has 30 years of senior management experience in the diagnostics industry. Prior to joining XDx, he held top management positions at Stone Bridge Management, Becton Dickinson, Bayer, Ortho (J&J) and Abbott. Mr. Cassigneul holds a management degree from Ecole Supérieure de Commerce de Reims, France.