This morning at the Sixth International Conference on Cell Therapy for Cardiovascular Disease, Aastrom Bio (ASTM) presented interim data from the first 40 patients at 6-months from the company’s IMPACT-DCM program. As a reminder, the Phase II IMPACT-DCM (surgical) program looked at the safety and efficacy of direct injection of Tissue Repair Cells (TRCs) into damaged areas of the myocardium. The trial was a prospective, open-label program with a crossover extension study for the control patients.
Baseline patient characteristic show a good distribution between both ischemic and non-ischemic subjects, with the majority of patients having significantly impaired ejection fraction (<30%) and are classified as NYHA III. These are “no option” patients heading towards transplant.
IMPACT-DCM Baseline Characteristics …
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Proof-Of-Concept Clearly Evident …
Proof-of-Concept is clearly evident by analyzing the data. Given the small size of the trial, no results are statistically significant, but the signs point to a quality of life benefit with TRCs. This will be explored further in a larger-scale phase IIb program to start later in 2011. The data notes an improved outcome for the ischemic DCM patients vs. the non-ischemic DCM patients.
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… Safety Assessment Looks Clean …
Given the baseline characteristics of very sick patients, that fact that there were no discontinuations due to adverse events and that events were pretty similar between the control and TRC group is highly encouraging. Post-surgery, there was no difference in the incidence of AEs across the TRC and control groups.
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We think the data above are clearly indicative of efficacy. Management will present full data from this program at the 12-month timeframe during the second quarter 2011.
… Cather-DCM Continues …
Management is also continuing enrolling patients in the phase II Catheter-DCM study to determine the safety and tolerability of administering expanded autologous cell therapy via a catheter (J&J’s NOGA) to patients with heart failure due to dilated cardiomyopathy. This trial completed enrollment at 23 patients in December 2010. Interim 6 month data from the Catheter study should be available in the third quarter 2011. The next step in DCM will be for Aastrom to meet with the U.S. to outline the design for a phase IIb study.
We expect the Phase IIb program will be a fully-control catheter program using the NOGA device. The trial will most likely seek to enroll about 100-150 patients with clearly objective endpoints such as heart function, 6-minute walk test, VO2 max, exercise capacity, or MACE. This will be large enough to clearly provide a roadmap for the phase III program, which we expect management will secure an SPA. We remind investors that the FDA has granted Orphan Drug designation to Aastrom for use of its TRCs in DCM. We are tentatively modeling this program to start in the calendar fourth quarter 2011, with data late 2012.
DCM is a condition in which the heart becomes weakened and enlarged, and cannot pump blood efficiently. The expansion of the heart and the decreased function results in poor blood circulation and affect the lungs, liver, and other body systems. In patients with DCM, the left or right ventricular systolic pump function of the heart becomes impaired, leading to progressive cardiac enlargement and hypertrophy, a process called remodeling.
There are an estimated 200k to 250k people living (prevalence) in the U.S. with DCM, with roughly 20,000 new cases (incidence) each year. About one in three cases of congestive heart failure (CHF) is due to DCM. The 1-year survival rate for a patient diagnosed with DCM is roughly 75%. The 5-year survival rate drops to only 30% because many patients with DCM go un-diagnosed until the disease has progressed to the most severe stages.
As a general rule for idiopathic DCM, after 1-year, 1/3rd of patients exhibit improved cardiac function, 1/3rd have stable cardiac dysfunction, and 1/3rd progress to significant cardiac dysfunction. These 1/3rd that progress to severe cardiac dysfunction will require a heart transplant.
Standard of care for patients with DCM is often to treat secondary co-morbid conditions such as hypertension or renal failure. As such, patients with DCM are often prescribed angiotensin-converting enzyme inhibitors, diuretics, beta-blockers, and sometimes digitalis. Anticoagulants may also be used. Artificial pacemakers and left ventricular assist devices (LVADs) may be used in patients with intra-ventricular conduction delay, and implantable cardioverter-defibrillators in those at risk of arrhythmia. These forms of treatment have been shown to improve symptoms and reduce hospitalization. They can cost upward of $75,000 each, and many patients will require re-implantation or an upgraded or new device in a year.
However, for patients with advanced disease who are refractory to medical therapy, cardiac transplantation is the only option. LVAD are commonly known as a "bridge to transplantation.” The problem however, and the reason this is such as a significant medical problem, is that only about 2,000 heart transplants are done in the U.S. each year. That means of the estimated 150k NYHA Class 3 or 4 patients with dilation, over 95% will never get a transplant. Accordingly, this is why mortality rates start to rise dramatically after a patient has been diagnosed with DCM.
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