Stem-Cell Therapy and Patient Safety – The Source Matters

Posted on February 6th, 2012

By Tim Mayleben
President and CEO of Aastrom

Dear Friends of Aastrom,

The issue of safety associated with stem-cell therapies has been in the news recently. Last month, the FDA issued a consumer update describing potential risks associated with the use of stem-cell therapies that have not yet been approved. Also recently, 60 Minutes ran a story about patients with severe illnesses who sought treatment with unapproved stem-cell therapies when no approved treatment options were available. In many cases, these patients paid vast sums of money and traveled to other countries to be treated with potentially dangerous and unregulated cell therapies.

These reports highlight the value of appropriate safety standards in the development of cellular therapies, standards which Aastrom maintains in all of its development, manufacturing and shipping procedures. These stories also raise an important issue about the different types of stem cells used in medical research and drug development, and the need to define clearly which cell types are being used. In many cases, the ethical or safety concerns associated with cell therapies relate to the use of embryonic stem cells, not the use of adult or autologous (“patient-specific”) stem cells which we use at Aastrom. Therapies derived from non-embryonic stem cell therapies are now approved for use in treating more than 70 medical conditions. ^{1, 2}

In the development of our cellular-medicine product, Aastrom uses the patient’s own bone marrow, which is collected in an outpatient setting. After the sample arrives at our laboratory in Ann Arbor, each step of the production process is carefully monitored to meet or exceed the safety and quality standards established by the FDA. After production, the final product, known as ixmyelocel-T, is then shipped back to the doctor for administration to the patient. While ixmyelocel-T is not yet approved for use in the United States, more than 400 patients have been treated with our product candidates in clinical trials.

This quarter we are advancing ixmyelocel-T to a Phase 3 clinical trial for the treatment of critical limb ischemia (CLI) and next quarter a Phase 2b trial for the treatment of dilated cardiomyopathy. Our Phase 3 REVIVE clinical trial in CLI will include 594 patients who have no option for revascularization and who have existing tissue loss. We have worked closely with the FDA, the Center for Biologics Evaluation and Research (CBER) and physician experts to design this trial and ensure that our production process and safety standards comply with all state and federal regulations.

As a developer of new cellular medicines, we believe stem-cell therapies have enormous therapeutic potential and can have a major positive impact on patients with serious, untreatable health problems. We also believe rigorous laboratory and clinical standards are essential to ensuring patient safety and public trust in our products. Aastrom is committed to employing the highest standards of pharmaceutical and medical practice as we advance our therapy toward final regulatory review.

As the field of cellular medicine continues to flourish, we have an obligation to distinguish the different types of stem cells used in the production process and support regulatory requirements for research, manufacturing and patient care that reflect these differences. Only those companies that maintain their commitment to the highest standards of safety and product quality warrant our support.

*For information about the FDA consumer update on stem-cell therapies, visit: http://www.fda.gov/ForConsumers/ConsumerUpdates/ucm286155.htm
**To see the 60 Minutes story about use of unapproved therapies, visit: http://www.cbsnews.com/video/watch/?id=7394380n
1. http://www.americansforcures.org/article.php?uid=1000
2. http://www.visionandvalues.org/2009/07/crucial-differences-between-non-embryonic-and-embryonic-stem-cells/

Unlocking the Potential of Regenerative Medicine

Posted on January 17th, 2012

By Tim Mayleben
President and CEO of Aastrom

Dear Friends of Aastrom,

Regenerative medicine is the term most often used to describe research and drug development involving the use of stem cells to stimulate the body to rebuild and repair damaged tissue.  Based on the results of multiple research programs in the U.S. and other countries, regenerative medicine has the potential to cure or reverse the symptoms of many diseases that affect different tissues in the body, including vascular, muscle, organ, bone and nerve tissues.

Today, the field of regenerative medicine encompasses many approaches to treatment, including:

• therapies administered by injection to promote tissue healing and organ regrowth;
• the growth of new tissue and organs in a laboratory for implantation in patients; and
• the use of biocompatible materials or small molecules to support the body’s natural ability to regenerate tissue.

At Aastrom, our approach to regenerative medicine is to use a patient’s own cells to develop a therapy that includes the optimal range and ratio of cells to treat severe, chronic ischemic cardiovascular diseases such as critical limb ischemia (CLI) and dilated cardiomyopathy.  The product we are developing, ixmyelocel-T, is personalized and custom-made for each patient from a small amount of his or her own bone marrow cells.  Our production process expands the numbers of certain key cell types – CD90+ mesenchymal cells, CD14+auto+ monocytes and alternatively activated macrophages – which, according to our research, seem to play an important role in tissue remodeling, immunomodulation and the growth of new blood vessels.

At the November 2011 American Heart Association Scientific Sessions, Aastrom reported positive results from the RESTORE-CLI Phase 2 clinical trial for ixmyelocel-T.  In this study, patients in the treatment arm showed a 62% reduction in risk relative to placebo in the primary efficacy endpoint of time to first occurrence of treatment failure (p = .0032) (Click here to read more about these results).  We plan to initiate the REVIVE Phase 3 clinical trial for ixmyelocel-T this quarter, making Aastrom the leading regenerative medicine company in the field of CLI and one of the few companies to have successfully advanced a cell therapy product to late-stage clinical development.

While there have been many important advances in regenerative medicine in recent years, developing new therapies in this field has been challenging.  Aastrom’s success in advancing ixmyelocel-T is the result of a number of key decisions and efforts by the Aastrom team:

• We are developing ixmyelocel-T as a treatment for severe, chronic ischemic cardiovascular diseases for which there are no other treatment options.
• We use only adult human stem cells from each patient’s own bone marrow.  As a result, our production process is not associated with the ethical issues surrounding the use of embryonic stem cells.  In addition, because we use the patient’s own cells to develop ixmyelocel-T, there is minimal risk of rejection.
• We collect a small amount of bone marrow and administer ixmyelocel-T rapidly in an out-patient procedure.
• We use a proprietary production process and a centralized cGMP manufacturing facility to ensure that every patient receives a safe, consistent, high-quality product derived from his or her own cells.
• Our development team is following a clear regulatory path established by other autologous cellular therapies that have been approved by the FDA in recent years.

These attributes distinguish ixmyelocel-T from other experimental cell therapies and have contributed to our success to date, but much work remains to be done.  To unlock the potential of regenerative medicine to improve human health in the years ahead, we believe swift action in several key areas is needed:

• We must encourage closer collaboration among leading academic research centers to identify and advance promising early-stage drug candidates to clinical-stage research conducted by industry partners.
• Additional sources of non-dilutive federal funding are needed to support research, early-stage drug development and job creation.
• We must continue to clarify and expedite the regulatory process for regenerative medicines by taking into account the unique production requirements and mechanisms of action of these therapies.
• Finally, we must continue to expand science education in the U.S. to train the next generation of innovators in cellular and regenerative medicine.
• Action will require careful planning, coordinated efforts and government action to be effective.  But if we take action now, I feel confident that we can realize the full potential of regenerative medicine in the coming decade and position the U.S. to maintain and expand our global leadership position in this rapidly evolving and highly promising field.

With regards,

Tim

Aastrom Nearing Launch of Phase 3 Revive Clinical Trial for Critical Limb Ischemia

Posted on December 9th, 2011

By Tim Mayleben
President and CEO of Aastrom

Dear Friends of Aastrom,

As you may have noticed, we recently redesigned the Aastrom website to help visitors access more information about our company. We hope this redesign makes it easier to learn about our work, mission and progress. To support the new site, we are also introducing a new blog about Aastrom where we will offer perspectives on important issues associated with our work and industry. I am very pleased to begin this new series with some comments on the disease that has been a primary focus of our work and research at Aastrom for the past several years—critical limb ischemia (CLI). (Learn more about critical limb ischemia or Aastrom’s CLI clinical trials, or watch the Living with CLI video.)

The importance of our CLI program cannot be overstated, as the need for a new treatment to help the millions of people affected by this terrible disease has never been greater. Having just returned from our clinical investigators’ meeting to prepare for the launch of our Phase 3 REVIVE clinical trial, I can attest to their excitement about evaluating our product candidate, ixmyelocel-T, as a potential treatment for people living with CLI who have no other treatment options. We are equally excited about the clinical and commercial potential of ixmyelocel-T following the positive results of our Phase 2b RESTORE-CLI clinical trial, which were presented in November 2011 at the American Heart Association Scientific Sessions.

CLI is a devastating and often fatal disease with few or even no treatment options available for many patients. In people with CLI, an obstruction of the arteries causes a decrease in blood flow to the extremities (hands, feet and legs). CLI is the most severe form of peripheral arterial disease (PAD). Currently, there are more than 10 million people living with PAD in the United States and one million people living with CLI.

In many cases, CLI results in a series of increasingly painful and challenging symptoms that can have a profoundly negative impact on a patient’s quality of life. These include:

• pain or numbness
• shiny, smooth, dry skin in the extremities
• nail thickening
• reduced pulse and blood pressure in the extremities
• development of sores, skin infections or ulcers that will not heal
• gangrene

These symptoms can lead to devastating health consequences, especially if they are not diagnosed early. Patients describe the pain associated with CLI as debilitating, making it impossible for them to complete many of the activities of normal life. People with CLI are often unable to sleep or relax without the use of the most powerful pain medications. In addition, the sores associated with CLI typically do not respond to conventional wound-healing treatments. As these wounds linger and progress, patients often develop gangrene and eventually require amputation—first minor amputations, but often ultimately leading to major amputation of the leg.

While there are many risk factors associated with CLI, the most prominent are a history of smoking, diabetes, obesity and atherosclerosis. Treatment options for earlier stages of CLI can include medications (statins, metformin, etc.), lifestyle changes including efforts to stop smoking, and open and endovascular surgical procedures to try to restore blood flow to the lower extremities.

My Aastrom colleagues and I are committed to finding a treatment for CLI and improving the lives of people afflicted by this devastating disease. Throughout our research we have been fortunate to meet and work with many of the world’s leading experts in vascular surgery and other specialties, as well as many CLI patients and their families, all of whom have helped us better understand the impact of this disease. During the past year, we have also worked closely with the FDA and key medical opinion leaders to develop the protocol for the Phase 3 clinical program we will be launching shortly. The REVIVE clinical trial will be the largest of its kind and an important test and milestone for ixmyelocel-T.

Thank you for visiting our site and taking time to learn more about Aastrom. We look forward to sharing new insights about our company and the patients we are committed to helping in the months and years ahead.

With regards,

Tim