Medical Device Daily
XDx (South San Francisco, California) earlier this month launched a test for the management of heart transplant patients in the hope that it will eliminate the need for potentially dangerous biopsies, the current method of determining if a heart transplant patient is rejecting the donor organ.
The test was launched at the International Society for Heart and Lung Transplantation’s (Addison, Texas) annual meeting in Philadelphia, where physicians demonstrated the use of what XDx calls AlloMap molecular expression testing. As such, the company said it is “one of the first practical applications of the human genome project.”
Heart transplantation “is where the need is the greatest,” CEO Pierre Cassigneul told Medical Device Daily. “It’s a very high-stakes situation where it’s literally a matter of life and death for patients, and the current methods of biopsy are not satisfactory for clinicians. So we felt that the need was compelling and also provided us with certain advantages for a start-up company.”
The current clinical practice for monitoring heart transplant rejection is endomyocardial biopsy. That procedure requires a small sample of tissue clipped from the heart and then analyzed by a pathologist.
With AlloMap testing, which received CLIA approval in November 2004, a clinician draws a tube of blood and sends it to the XDx reference lab.
“They process it, because we need to extract the cells from the blood sample immediately, because . . . the immune system in the blood continues to express the gene, so we need to stop that reaction, extract the cells, and they are sent by FedEx overnight to us,” Cassigneul said.
The XDx lab begins its processing of the patient’s blood the day it is received, and following quality control procedures the next day, the lab provides a report to the clinician – about 48 hours for the whole process. That is the typical amount of time it takes to complete the traditional endomyocardial biopsy. XDx’s test, however, distinguishes rejection vs. lack of rejection, also known as quiescence, by detecting mobilization of the alloimmune response, rather than through graft damage with biopsy.
XDx also says that its test may detect rejection that could not be determined through a graft.
To develop AlloMap testing, XDx evaluated more than 25,000 gene sequences and, using microarray and real-time polymerase chain reaction technology to measure gene expression, developed a 20-gene algorithm specifically correlated with rejection. The AlloMap test translates gene expression information into “a single, actionable score,” the company said.
While cardiologists have been “incredibly successful at managing” their transplant patients, said Cassigneul – the survival rate at 10 years is about 50% – it usually is enabled by the use of potent immunosuppressive drugs. Those drugs, at about 10 years after the transplant, frequently begin causing problems for the patient, including infection and cancer, because the immune system has been suppressed in order to avoid rejection of the implanted heart.
Another goal of the test is to help cardiologists titrate the drugs, so that patients only get the least amount that they need to both prohibit rejection, yet avoid potential long-term side effects of the medication.
The original concept for the test was identified in 1998, and XDx was founded in 2000. Today, one of the three founders of the company is an employee, while the other two are board members.
Although the concept started out a little broader in scope, in 2001 they began to focus on heart transplantation. One of the advantages of this area of focus was that there are only 200 transplant centers in the U.S., where about 2,300 heart transplants are performed each year. Worldwide, about 4,500 heart transplants are performed annually. The U.S. centers “tend to be closely-knit communities where, if you can convince a few of the leading centers, others will tend to observe and follow. It’s easier for us to do than to reach thousands and thousands of physicians,” Cassigneul said.
He said that the company will be able to reach of about 800 cardiologists associated with the U.S. centers with a small sales and marketing staff.
On the payment side, XDx is seeking reimbursement for the test. However, Cassigneul said that many payers already are reimbursing for the test.
“The important thing is that the Allomap has been designed and priced so that it would actually generate cost savings to the system. Even though it’s new technology, [it] costs less than the current system of biopsies,” he said.
While it can go it alone in the U.S. for heart transplant testing, the company is in the process of forming a partnership in Europe in order to set up the same type of reference laboratory it has here.
XDx also is planning to use its technology to be used on all autoimmune diseases, such as rheumatoid arthritis and Crohn’s disease, which multiplies the number of patients affected to about 20 million.
Cassigneul said the company would be seeking partnerships in the U.S. to reach that market in the future.