June 12th, 2013
During our first-quarter earnings call last month, I was pleased to report that we began treating patients in the ixCELL-DCM Phase 2b trial, which is evaluating ixmyelocel-T for the treatment of advanced heart failure due to ischemic dilated cardiomyopathy (ischemic DCM). This clinical trial offers a potentially historic advancement in the treatment of patients with advanced heart failure due to ischemic DCM, an indication for which we have an orphan drug designation in the United States.
DCM is a condition in which the heart becomes weakened and enlarged and cannot sufficiently pump blood throughout the body. DCM is the third most common cause of heart failure and the most frequent cause of heart transplantation. A majority of the advanced heart failure patients who no longer respond to medical therapy — more than a quarter of a million patients in the U.S. — have DCM, and approximately 60% of these cases are of ischemic origin due to prior heart attacks or atherosclerosis. These patients typically have maximized their use of prescription and device therapies, and are no longer candidates for procedures to restore blood flow such as angioplasty and bypass surgery. At this stage of the disease, they have very limited treatment options, which generally include placement of left ventricular assist devices and heart transplantation.
What makes advanced heart failure due to ischemic DCM so challenging for patients is its impact on daily life. The condition significantly reduces exercise capacity and quality of life, because for many patients, walking even a short distance causes severe shortness of breath and fatigue. There is a strong rationale for developing ixmyelocel-T for the treatment of ischemic DCM. In preclinical studies, ixmyelocel-T was found to significantly reduce cardiac tissue damage and demonstrated additional cardioprotective effects in relevant disease models. In Phase 2a clinical trials, ixmyelocel-T was found to be well-tolerated and demonstrated positive efficacy trends, including improved symptoms and improved walking distance in treated patients compared to placebo.
The ixCELL-DCM Phase 2b trial is designed to enroll 108 patients at about 30 sites in the U.S. and Canada. This is a double-blind, placebo-controlled trial that will primarily measure mortality, hospitalizations, and heart failure emergency room visits in trial participants. The trial also will examine a range of clinical, functional, and symptomatic measures. The study is on track to complete enrollment by the end of Q1 2014 and show top-line results in Q2 2015.
Aastrom is one of the few companies working to develop a treatment for this major unmet medical need, and our clinical research program for ixmyelocel-T is one of the most advanced global research efforts in regenerative medicine. As we continue to make progress, we look forward to the opportunity to share our results and insights with patients, physicians, and researchers around the world.
May 6th, 2013
As my colleagues at Aastrom participate in important medical meetings on regenerative medicine and cellular therapy, we can see why 2013 has been named the “Year of the Stem Cell” by The Atlantic magazine. The medical community is excited about the therapeutic potential of regenerative medicine and our unique multicellular product candidate ixmyelocel-T is attracting great interest as a promising new treatment modality for serious cardiovascular diseases such as advanced heart failure due to ischemic dilated cardiomyopathy.
It is well understood that there are multiple cell populations and multiple signaling pathways involved in the disease progression involving tissue injury, chronic inflammation, and the resulting tissue damage that leads to loss of organ function, as well as the processes involved in the repair and regeneration of damaged tissue. Therapeutic approaches targeting single signaling pathways in these complex disease and repair processes have not proven effective, and most cell therapy approaches expand a single cell type to attempt to arrest manifestations of the disease. Aastrom is taking what we believe is a highly differentiated and superior therapeutic approach by developing multicellular therapies that utilize an expanded population of the key cell types that the body naturally uses to repair and regenerate damaged tissue.
Ongoing discovery research by Aastrom scientists and our outside collaborators continues to define the mechanism of action of ixmyelocel-T and differentiate our product from other cell therapies based on the activity of the two key cell populations in ixmyelocel-T: mesenchymal stromal cells (MSCs) and M2-like anti-inflammatory macrophages. These key cells have multiple direct activities and beneficial effects on nearby cells that have been shown to promote tissue repair and regeneration by reducing inflammation and promoting angiogenesis and remodeling of damaged tissue. Based on the activities of these cells and the resulting therapeutic effects, Aastrom’s unique multicellular therapy platform offers the potential for multiple therapeutic applications in treating cardiovascular and other fibrovascular disorders of the lungs, liver, kidney and other organs.
There is enormous therapeutic potential for ixmyelocel-T based on its multicellular composition and the promising results in the treatment of ischemic or damaged tissue demonstrated in preclinical and clinical studies conducted to date. We look forward to generating results in our current ixCELL-DCM phase 2b study of ixmyelocel-T for the treatment of advanced heart failure due to ischemic dilated cardiomyopathy, and continuing to explore the potential therapeutic effects of ixmyelocel-T to repair and regenerate damaged tissue in other severe diseases.
April 4th, 2013
Our recent decision to implement a strategic change in our R&D programs to focus on the development of ixmyelocel-T for the treatment of dilated cardiomyopathy (DCM) and stop enrollment in the Phase 3 REVIVE trial in critical limb ischemia (CLI) reflects the significant opportunity that we see to treat advanced heart failure caused by DCM and the challenges that we faced in enrolling the REVIVE study in a reasonable timeframe. While we believe that ixmyelocel-T has strong therapeutic potential to treat CLI, based on previous clinical results showing that ixmyelocel-T was efficacious and well-tolerated in this patient population, the decision was based on our need to allocate resources to advance ixmyelocel-T toward commercialization as quickly as possible. We believe that the DCM program represents our best near-term opportunity to accomplish this goal.
Our previous results in DCM —in both preclinical and clinical studies — suggest that our patient-specific multicellular therapy can produce a range of clinical benefits for patients with severe heart failure whose limited treatment options include heart transplantation. Read More…
February 1st, 2013
Dear Friends of Aastrom,
February is American Heart Month, and it is during this time that we recognize many of the important advances in medical research that may help us prevent and treat cardiovascular disease more effectively. In recent years, breakthroughs in surgery, drug therapy and devices have expanded options for patients, making it possible to lower the risk of a cardiac event and treat the effects of peripheral artery disease (PAD). Despite these advances, cardiovascular disease remains the leading cause of death in the United States. Each year it disrupts the quality of life of millions of people and is the cause of approximately 160,000 amputations and 1.5 million heart attacks in the U.S.
Fortunately, there are reasons to be optimistic. Recent advances in regenerative medicine and cell therapy are encouraging and have shown the potential to improve the lives of patients with the most severe forms of cardiovascular disease. In preclinical and clinical studies, cell therapies have demonstrated the potential to repair damage to the heart muscle and other vascular tissue that can occur with a cardiac event. They also have the potential to help restore blood flow or repair genetic defects. If we continue to make clinical progress in this area, cell therapies may become an effective, less costly treatment option for people with advanced cardiovascular disease. Read More…
January 1st, 2013
Dear Friends of Aastrom,
As the new interim chief executive officer of Aastrom Biosciences, I am honored to lead the company as we continue to advance the clinical research programs for our lead product candidate, ixmyelocel-T. I believe we have a unique opportunity to improve the lives of people with severe, chronic cardiovascular diseases with ixmyelocel-T, and am very pleased to have the opportunity to bring my experience building successful pharmaceutical brands to this development program as we begin to formulate plans related to commercialization. Since I joined Aastrom in August as chief commercial officer, I have seen firsthand the potential of our technology to treat these diseases and the dedication of our team to bring this promising therapy to patients who may benefit from it. Read More…
December 1st, 2012
Dear Friends of Aastrom,
Aastrom’s commitment to transparency was reinforced by the recent announcement from GlaxoSmithKline (GSK). GSK made headlines when it announced a new policy to disclose all clinical data from the company’s drug development programs. Previously, the company had followed prevailing industry standards by releasing results from only some of its clinical studies (generally, only the positive ones). A 2008 study[i] by the University of California, San Francisco found that many drug companies do not routinely report negative clinical data, while some do not make any data available to the public. We welcome GSK’s initiative – it is good clinical practice and consistent with our commitment to transparency at Aastrom. This move toward greater transparency is an important trend with profound implications for the future of research.
We believe that the benefits of disclosing all clinical results, not just the positive study results, far outweigh the real or perceived risks. Full disclosure allows any interested party to review all of the potentially relevant data about experimental therapies. This allows for a much broader and more accurate assessment of both safety and efficacy – the mechanisms of action – and also enables scientists and physicians to identify potential areas for future research. When publicly available information is incomplete, it can lead the medical community to flawed conclusions that may limit the chances of future clinical success or, in extreme cases, actually cause patients harm.
November 1st, 2012
Dear Friends of Aastrom,
There have been many studies over the years highlighting the fact that drug discovery and development is typically a very long, risky, complex and costly process. It is not uncommon for drug development programs to last a decade or more, beginning with early-stage discovery and research, and progressing through late-stage clinical development, regulatory review and approval. Within that timeline, companies must continually monitor progress and determine when and whether to expand their focus to include essential commercialization strategies to prepare to bring promising late-stage product candidates to the patients who need them.
Over the past year, Aastrom has initiated a number of important activities to support the future commercialization of ixmyelocel-T, which is currently in Phase 3 clinical trials for the treatment of patients with severe peripheral arterial disease (PAD) and existing tissue loss, and in Phase 2 trials for the treatment of patients suffering with dilated cardiomyopathy (DCM). Read More…
July 5th, 2012
Dear Friends of Aastrom,
Dilated cardiomyopathy (DCM) is a progressive disease of heart muscle. It is now the third most common cause of heart failure, which affects approximately 4.9 million people in the United States (www.americanheart.org). Dilated cardiomyopathies are associated with both systolic abnormalities (difficulty of the left ventricle to empty or eject blood from its chamber) and diastolic abnormalities (increased resistance to filling of one or both ventricles). The progression of DCM can be rapid; studies have found that 50 percent of the deaths from DCM occur within two years of diagnosis (http://health.usnews.com).
Currently, there is no cure for DCM, but cardiac medications, lifestyle changes and implantable devices can help to control some symptoms. When these treatment options can no longer control symptoms of DCM, heart transplantation may be the only option for many patients – in fact, DCM is now the most frequent cause of heart transplantation (www.americanheart.org). Unfortunately, there are only enough donors for about 2,000 heart transplants each year. More than 95% of patients with moderate or severe heart failure (NYHA Class III or IV) will not be able to get a transplant. (Zacks)
One sign of hope is research showing that mesenchymal cells, monocytes and alternatively activated macrophages can have a positive impact on heart muscle and function damaged by DCM. Read More…