Organ rejection is the chief concern for heart transplant patients long after surgery is completed. They have to revisit physicians on a regular schedule to insure that their bodies are not rejecting the foreign tissue and current tests to check for rejection are invasive and dangerous.

XDx (Brisbane, California) has received market clearance from the FDA for AlloMap Molecular Expression Testing, a blood test used to aid in the management of heart transplant patients after surgery. AlloMap will eliminate the need for endomyocardial biopsies, the current method used to determine if a heart transplant patient is rejecting the donor organ. That procedure requires a small sample of tissue clipped from the heart and then analyzed by a pathologist.

"AlloMap indicates whether or not a heart transplant patient is at risk of acute cellular rejection," XDx president/ CEO Pierre Cassigneul told Medical Device Daily. "When the heart is transplanted into a patient, the immune system of the patient is designed to attack foreign elements like a virus or a transplanted heart. This clearance and the FDA's focus on this field underscore the growing importance of molecular diagnostics in the care of patients."

The blood test — which costs $2,950 — would be performed at as many intervals as suggested by the physician. Heart transplant patients have a survival rate of 50% at 10 years. The powerful immunosuppressive drugs frequently begin causing problems, including infection and cancer, because the immune system has been suppressed in order to avoid rejection of the implanted heart.

AlloMap assays the RNA levels of 11 rejection biomarker genes and nine control genes. When these genes turn on or off, the white blood cells respond by either quieting down or increasing their activity, which can cause rejection.

XDx developed AlloMap using blood and biopsy samples and other information collected from heart transplant recipients at nine U.S. heart transplants centers participating in the Cardiac Allograft Rejection Gene expression Observational study (CARGO). CARGO provided data from 153 patients on 300 medical visits at various times after heart transplant study.

AlloMap is just the fourth in vitro diagnostic multivariate index assay (IVDMIA) cleared by the FDA. IVDMIAs are medical devices that combine the values of multiple variables to yield a single, patient-specific result.

Development of a similar test, for lung transplant patients, will be completed by XDx by the end of 2009.

Cassigneul said XDx plans to spin the same technology out in a series of tests aimed at better management of immune-mediated conditions such as lupus, multiple sclerosis and rheumatoid arthritis.

"Physicians try to minimize damage that flares cause in these diseases," Cassigneul said. "We're developing tests [based on the same AlloMap technology] to provide a flare predictor so physicians can act before they see symptoms of flare." He expects the first of those tests, for lupus, to be ready for market by 2011.

XDx launched the AlloMap in 2005 after receiving CLIA approval in November 2004. But further FDA review was required for U.S. marketing.

"We had to comply with CLIA," Cassigneul said. "But since then, the FDA has expressed intentions to regulate this type of test further."

Last year the FDA issued draft guidance, explaining that the agency seeks to identify IVDMIAs as a discrete category of device, and to clarify that IVDMIAs must meet pre- and post-market device requirements under FDA regulations, including premarket review requirements in the case of most class II and III devices.

IVDMIAs are medical devices that combine the values of multiple variables to yield a single, patient-specific result. Other IVDMIAs that have received FDA clearance include:

• MammaPrint, developed by Agendia (Amsterdam, the Netherlands), is used to determine the likelihood of breast cancer returning within five to 10 years after a women's initial cancer (MDD, Feb. 7, 2007)

• The Pathwork Tissue of Origin test, developed by Pathwork Diagnostics (Sunnyvale, California) and approved last month, helps healthcare professionals determine what specific type of cancer cells are present in a malignant tumor (MDD, Aug. 4, 2008).

• The Previstage GCC Colorectal Cancer Staging Test, for which DiagnoCure Oncology Laboratories (West Chester, Pennsylvania) received certification last month to help answer the fundamental question that every colorectal cancer patient asks after surgery: "Am I cured or has my cancer spread?" (MDD, Aug. 28, 2008).

Not only is XDx the only company producing a test of this kind, it also has cornered the market on lab processing. All blood samples are sent to its own reference labs.

Cassigneul said that, of the 190 heart transplant centers in the U.S., about 70 have ordered the test with some frequency already.

"Last year we had sales of $10.3million with that test alone," he said, which has also been launched in the European Union.

Medicare already is providing reimbursement, but private insurers are continuing to review reimbursement for AlloMap "on a case-by-case basis," Cassigneul said, adding that FDA clearance "will provide a rationale for payers to pay for the test."

XDx last October filed for an initial public offering. "We intend to go public sometime, [but] unfortunately the market conditions are not favorable right now," he said. The company will seek a private round of financing this year to keep moving its business forward.