By Patrick Crutcher
Aastrom Biosciences, Inc. (ASTM) has captured investors' attention the past few weeks concerning their upcoming catalyst. The data being presented on November 18th has major implications for the future of Aastrom. With this in mind, we contacted management with some questions.
Aastrom will be giving an update on their Phase 2b trial in critical limb ischemia (CLI) via satellite at the VEITHsymposium on November 18, 2010 at 1:00 pm EDT. The event will feature a presentation by Richard Powell, MD, Principal Investigator in the RESTORE-CLI clinical trial, as well as a Q&A session.
Aastrom is investigating the use of their Tissue Repair Cell (TRC) technology, which is an autologous based platform, for the treatment of cardiovascular diseases. This technology allows them to significantly expand the number of stem and progenitor cells than what would normally be present in the patient’s bone marrow. After the bone marrow is processed with Aastrom’s technology, the mixture of cells is then injected back into the same patient to help repair and regenerate tissue. They are currently running 2 major clinical trials: CLI and dilated cardiomyopathy (DCM), both in Phase 2.They have recently filed for an SPA for their Phase 3 program in CLI and expect to report interim results from their IMPACT-DCM trial sometime in January. The markets for DCM and CLI are substantial (several billion), lack competitors and represent a significant unmet medical need.
We reached out to President and CEO Tim Mayleben, as well as Vice President of Clinical and Regulatory Dr. Sharon Watling, for answers. The following is a transcript of that interview:
BioMedReports: Has ASTM considered partnering their TRC treatment for CLI? Are there any ongoing negotiations or interest? If ASTM plans to partner its technology, when will it seek a partner? After SPA approval is obtained?
ASTM: Aastrom does, and will continue to, evaluate partnering opportunities. However, we are excited about our technology, our stage of development, our experienced development team, and the indications in CLI and DCM that we’re pursuing. We are confident in our ability to conduct and fund the development of our programs but will consider alternatives, such as partnering, if they are economically and operationally attractive.
BioMedReports: ASTM will be doing injections of TRCs into CLI compromised limbs. How are these injections performed? What are the area spacings of injections? How much volume is injected at each site? How do you map the injection sites for consistency between patients? Could you go over some of the guidelines for the procedure?
ASTM: As with all clinical trials, the specifics of our treatment are outlined in the investigators brochure. Our treatment begins with a very small bone marrow aspirate, approximately 50 mL, taken from the patient’s hip bone (illiac crest) in a 20-minute outpatient procedure under conscious sedation or local anesthesia. The bone marrow aspirate is then sent to our cell manufacturing facility and, over the course of 12 days, we manufacture our expanded autologous cell therapy product. The expanded cell therapy is sent back to the physician. Our physician investigators then inject the cell therapy product into the index leg of CLI patients in a single, 15-minute outpatient procedure. Approximately 20 intra-muscular injections are performed in the treatment with spacing determined by the physician using the guidance provided in our study manual associated with the clinical protocols. Each injection is small, < 0.5mL and is injected circumferentially around the index limb in specific quadrants down the leg.
BioMedReports: Will your Phase 3 trials split the patient populations into two groups: diabetics who have notoriously worse healing than the general population and non-diabetics with PAD?
ASTM: Our Phase 3 protocols have been submitted to FDA through the Special Protocol Assessment process. Once we have finalized the Phase 3 protocols through discussions and negotiations with FDA we will be able to comment more specifically. It’s important to note diabetes alone is not the key determinant for success or failure of treatment for CLI patients.
The most comprehensive understanding of the risk factors associated with outcome is incorporated in a Conte paper from Journal of Vascular Surgery (Conte et al, Dec. 2009, Journal of Vascular Surgery; Vol 50(6),1462-1473) and the accompanying website www.criticallimb.org. These meta-analyses suggest that a critical component of risk for events is underlying tissue loss, which is defined as wounds or gangrene. Because of the impact of this, we have incorporated this learning into our Phase 3 planning. We recognize that diabetes increases the probability of developing PAD and CLI. Accordingly, in our Phase 2 trial roughly 60% have diabetes at baseline and we expect the same in our Phase 3 program.
BioMedReports: Can you give us an update on enrollment in the Catheter-DCM trials?
ASTM: We expect enrollment in the catheter trial to complete by December 2010.
BioMedReports: In regards to the IMPACT-DCM trial, can we expect results from this trial sometime in Q1 2011?
ASTM: We expect that the interim analysis of our Phase 2 IMPACT-DCM surgical trial will be presented at a scientific meeting in January 2011. Details on that meeting and presentation will be announced shortly.
BioMedReports: How is administration of TRCs performed for DCM? Superior Vena Cava versus coronary artery administrations via femoral sticks might well have different efficacies. Another approach would be direct cardiac injections of TRCs via a robot assisted transthoracic approach that conceivably would have the greatest efficacy. Still another approach would be intermittent injections of TRCs over a week's time through a supraclavicular route to the right atrium. One approach may not rule out the efficacy of an alternate approach. Are other approaches being considered for the administration of TRCs for DCM?
ASTM: We have investigated a surgical approach in which a mini thoracotomy is performed and the cells are directly injected in the peri-infarct area (for ischemic patients) and in an extensive pan-LV approach in non-ischemic patients. In catheter, the cells are delivered by percutaneous catheter injection into the endothelium of the LV. These injections are also in the peri-infarct region. We continue to consider and investigate other approaches.
BioMedReports: Has ASTM considered using TRCs in other future indications? In the past ASTM explored long bone fractures.
ASTM: Aastrom has an active research and development department looking at potential future indications for our expanded autologous cell therapy. As these research efforts mature and move into development, we will present and publish this work.
Disclosure: Long ASTM