Aastrom's cardiac repair cells for dilated cardiomyopathy fails to impress physicians due to modest
effects, delivery concerns
by Jacqueline Kwong in New York
 Patient enrollment for Phase II to be completed by end of 2009
 Injecting CRCs into the heart wall has low engraftment rate because a heart pulse will cause cells to eject from the wall
 With Aastrom's current delivery technique, only 10% of the CRCs become engrafted into the Heart
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Aastrom’s (NASDAQ:ASTM) cardiac repair cells (CRCs) for dilated cardiomyopathy (DCM) have a modest effect due to delivery
concerns, physicians said. An improvement in delivery techniques could increase their efficacy, they added.
Aastrom’s CRCs are in Phase II trials for the treatment of dilated cardiomyopathy and the company is completing patient enrollment
for the trials. Patients with end-stage heart failure are being recruited for these trials, such as those with Stage III and Stage IV heart
failure. Patients must also have controlled dilated cardiomyopathy with current medical therapies.
The Phase II trials will run for approximately one year with a primary endpoint of time until a major cardiac adverse event, which
includes cardiac death, cardiac arrest, and myocardial infarction. Patient enrollment will be completed by the end of this year.
Aastrom’s CRCs are a combination of stem cells and progenitor cells cultured from the patient’s own bone marrow. After extracting a
small portion of bone marrow from the patient, Aastrom purifies stem and progenitor cells from the bone marrow, and expands the
cell population. These cells are then injected back into the patient’s heart, in which the cells hopefully differentiate into healthy heart
muscle cells.
Progenitor cells are like stem cells, as they have the ability to differentiate into a specific cell type. However, progenitor cells are
limited to differentiating into one specific cell type whereas stem cells may have the ability to differentiate into a variety of cell types.
The evidence currently shows that CRCs have a modest and transient effect in patients, said Dr. Kenneth Chien, the director of the
MGH cardiovascular research Center at the Harvard Stem Cell Institute. This therapy is not greatly efficacious because few CRCs get
into the heart, and even fewer of them turn into heart cells, he noted.
A spokesperson from Aastrom noted that preclinical and clinical studies indicated that there was no limited duration to the
effectiveness of the therapy. Aastrom’s technique of delivering CRCs to the heart results in a low engraftment rate, noted Dr.
Glenn R. Gaudette, an assistant professor of biomedical engineering at Worcester Polytechnic Institute. Less than 10% of the cells get
into the heart, because when the heart pulses, it ejects cells from the cardiac wall - where the CRCs are injected, he explained. This
indicates that few CRCs will differentiate into heart cells, he said.
Dr. Antonio Carlos de Carvalho, a professor of physiology and biophysics at Federal University of Rio de Janeiro, agreed that the
efficacy of this treatment was questionable. Aastrom’s technique of delivering the CRCs, by making a small incision in the ribs and
injecting the cells into the myocardium, is practical but it allows few cells to make it to the heart, he said. Furthermore, studies have
shown that this treatment lasts only for six months, which may require patients to undergo several treatments, he added. Receiving
repeated incisions in the ribs may become problematic for patients, noted Carlos de Carvalho.
When asked about different delivery techniques, Gaudette and Dr. Marc Penn, the medical director of the cardiac intensive unit at the
Cleveland Clinic, both pointed to alternative methods. Cells could be grown on a scaffold and implanted on the outside wall of the
heart, according to Gaudette. This method results in a higher rate of engraftment, but is not as non-invasive as Aastrom's method, he
added. Penn noted that he was currently working on placing "homing" factors in the heart to enhance stem cell targeting, which would
increase the engraftment rate. Gaudette said such improved delivery techniques should be available in a couple of years.
Aastrom's therapy should be limited to end-stage heart failure patients who have no other options for medical treatment, said Carlos de
Carvalho. For these patients, the benefits of potentially alleviating heart disease outweigh the risks of receiving multiple incisions, he
noted.
Penn agreed that six months of potential disease improvement was very beneficial for end-stage heart failure patients. These patients
are very ill and have a 30% chance of death, said Penn. Giving these patients an additional six months to live is better than nothing, he
added.
The hope is that by injecting CRCs into the heart, heart cells will be regenerated and the stem cells will help vascularize the heart, said
Gaudette. Unfortunately, that theory has yet to be proven, he added. However, when asked whether the FDA would require the
mechanism of CRCs to be known, Gaudette said it was unlikely it would be required for approval. Aastrom has a market cap of USD
59.54m.