Targeting CLI: A Major Unmet Need for Patients and a Significant Opportunity for Aastrom
Dear Friends of Aastrom,
Over one million people in the U.S. are living with critical limb ischemia (CLI), a severe form of peripheral arterial disease (PAD). CLI is a devastating and often fatal disease where blood flow to extremities is restricted, resulting in debilitating pain, life-threatening infections, loss of limbs, and death. There are currently no FDA-approved therapies to treat CLI; the most frequent treatment option is revascularization surgery to restore blood flow to affected areas. However, all too often, especially for very ill CLI patients, revascularization surgery is not effective. At Aastrom we are applying our proprietary cell-processing technology to develop an entirely new approach to the treatment of CLI.
The Challenge in Treating CLI
CLI is caused by chronic inflammatory processes associated with atherosclerosis. In patients with CLI, arterial plaque restricts blood flow to the legs, feet and hands, leading to pain, numbness, open sores, skin infections, ulcers, and gangrene. Major amputation is often the only treatment alternative when overwhelming infection threatens a patient’s life, rest pain cannot be controlled, or there is extensive skin and tissue loss.
The risk of CLI is higher among people with diabetes, high cholesterol levels (dyslipidemia), and renal failure. The elderly and people who are smokers, sedentary, or overweight are also more likely to develop CLI. There are few treatments for CLI today; patients are generally prescribed medications to relieve pain and instructed to improve some risk factors. While revascularization surgery to restore blood flow is an option for some, up to 40% of CLI patients are not candidates for surgery and are considered “no-option.” In addition, revascularization surgery is often unsuccessful. From 35% to 85% of surgeries for no-option CLI patients are unsuccessful, depending on the presence of other risk factors (such as diabetes or renal failure). Researchers are studying a range of options to treat CLI, including the use of growth factors, protein therapies, and cell-based therapies.
A Strong Fit for Aastrom’s Cell-Processing Technology
As the leader in the development of patient-specific, expanded multicellular therapies to treat severe, chronic cardiovascular diseases, Aastrom is committed to finding an effective therapy for patients with CLI who have no other treatment options. We believe our proprietary cell-processing technology and investigational product, ixmyelocel-T, are unique among cell therapies because we start with the patient’s own cells. Our production process expands the numbers of certain key cell types found in the patient’s bone marrow stem cells, including CD14+auto+ monocytes and alternatively activated macrophages to reduce chronic inflammation, and CD90+ mesenchymal stromal cells for tissue remodeling and growth of new blood vessels. The resulting therapy includes the optimal range and ratio of these and other cells to treat the multi-factorial disease that is CLI.
While ixmyelocel-T is not yet approved for use in the United States, more than 200 patients have been treated thus far in our clinical trials, and initial results are encouraging. In November 2011, we presented the results of our Phase 2b RESTORE-CLI clinical trial, which demonstrated that treatment with ixmyelocel-T improved time to treatment failure by 62% in patients with CLI compared to the control group. Equally important, the most severely ill CLI patients – those patients with wounds at baseline – demonstrated an improvement in amputation-free survival. In the first quarter of this year, Aastrom initiated the REVIVE Phase 3 clinical trial for ixmyelocel-T. In this study, 594 CLI patients will be treated at 80 treatment centers in the United States.
Targeting a Major Commercial Opportunity
Without treatment, many “no-option” CLI patients will die or undergo a major amputation of a limb, which reduces their quality of life and ability to participate in many daily activities. According to The Amputee Coalition, nearly half of all people who have an amputation due to vascular disease will die within five years, a higher five-year mortality rate than breast cancer, colon cancer, or prostate cancer patients. Nearly 60% of amputations are paid for by Medicaid and Medicare, costing taxpayers more than $5.2 billion in 2008. In 2009, hospital costs associated with amputation totaled more than $8.3 billion.[i]
We look forward to completing our Phase 3 testing program in CLI and finding other unmet medical needs where we can apply our innovative cell-therapy technology and drug development expertise to develop new treatment options for patients and sustainable long-term value for our shareholders.