Cardium Therapeutics (NYSE Amex: CXM) today reported that a recent medical journal article highlights the challenges facing healthcare providers with respect to finding optimal treatments for patients with non-healing wounds.
As reported in the Journal of the American Academy of Physician Assistants, (JAAPA, August 2009), chronic wounds affect an estimated 5.7 million patients in the U.S. and cost the healthcare system approximately $20 billion annually. The article's author further notes that optimal wound care requires a portfolio of treatments including the only FDA-approved protein-based topical gel Regranex(R) (becaplermin), bioengineered skin substitutes, hyperbaric oxygen therapy, and subatmospheric wound therapy (also known as negative-pressure wound therapy), as well as institutional support from the growing number of nationwide wound-care centers that offer specialized, multidisciplinary approaches to the treatment of chronic wounds. The author also reports that the cost of treating non-healing ulcers of longer than one year's duration is estimated to range from approximately $20,000 to $27,000, based on the level of advanced care.
As reported in the International Wound Journal, (December, 2007) "one of the most feared complications of diabetes is the lower extremity amputation." Other studies report that diabetes is the leading cause of nontraumatic lower extremity amputations in the U.S., amounting to greater than 75,000 per year or over 200 per day. Limb amputation occurs 10 to 30 times more often in a diabetic person than in the general population. Among the patients with lower extremity amputation procedures, 5% to 17% will die during the operation and 2% to 30% will die within 30 days of surgery. Longer term survival is even worse. Mortality following amputation ranges from 13% to 40% at one year, 35% to 65% at 3 years and 39% to 80% at 5 years. These mortality rates are similar or worse than many common types of cancer including prostate, breast, colon and Hodgkin's disease. Despite these grim statistics, many remain unaware of the very serious nature of non-healing lower extremity ulcers in diabetic patients.
Innovative Advanced Care DNA-Based Therapy
Cardium's Excellarate(TM) product candidate is a collagen-based topical gel employing Tissue Repair Company's (TRC's) Gene Activated Matrix(TM) that is designed to locally stimulate the release of platelet-derived growth factor-B protein (PDGF-B), an important key in the human body's wound healing process. Sustained, localized micro-release of PDGF-B by a patient's own cells directly at the wound site is believed to stimulate angiogenesis and granulation tissue formation through the recruitment and proliferation of cells such as monocytes, fibroblasts and endothelial cells. These cell types are critical for the effective stimulation of a variety of wound healing processes.
Excellarate is an advanced care DNA-based biologic product candidate that is being developed to provide physicians and patients with a potentially simpler, easy-to-use treatment as compared to current therapies. Based on the positive data from a Phase1/2 study, the Company believes that the Excellarate topical gel provides a unique opportunity to: (1) improve patient compliance, based on a one or two physician administered treatment regimen, instead of current therapies which require multiple treatments by physicians or patients on a daily or weekly basis for up to 20 weeks, and (2) enhance acceptance by the medical community due to improved ease of use (as a pre-filled syringe, requiring only standard refrigeration and a 15-18 month shelf life), when compared to other treatment options.
With this targeted registration profile, Cardium believes that Excellarate offers the unique potential to become an important new therapeutic class that, in certain cases, may supplant the use of current healing agents and medical devices, and, in certain wounds and under various medical conditions, may be used in concert with other agents and current therapies within an expanding spectrum of advanced wound care solutions. The Company believes that, because of the complex nature of lower extremity diabetic ulcers, patients will benefit from the availability of a multitude of wound healing agents and therapies that can be tailored to appropriately address their specific medical conditions.
Benchmarks with Current Therapy
Regranex Topical Gel - As referenced in JAAPA, current therapy includes the use of a topical protein-based growth factor gel, Regranex (becaplermin; 0.01% recombinant platelet-derived growth factor-B). Regranex is currently the only FDA-approved advanced care biologic topical agent for the treatment of patients with lower extremity neuropathic diabetic foot ulcers. It was initially developed by Johnson & Johnson and is currently marketed by Systagenix. Regranex which is patient administered, requires daily application followed by a daily cleansing 12 hours after the drug treatment over a 20-week period. As a result, during the prescribed 20-week treatment period, Regranex patients are required to undertake approximately 280 interventions (drug administrations and cleansings) to achieve the potential maximum healing effect.
Bioengineered Skin Substitutes - In addition to protein-based therapy, the JAAPA article discusses other advanced wound healing approaches for the treatment of diabetic foot ulcers that include bioengineered skin substitutes, as well as medical devices that provide negative pressure wound therapy. Bioengineered skin substitutes represent an important class of products that include two FDA-approved dermal graft substitutes: Apligraf(R) a combination of human fibroblasts and keratinocytes and Dermagraft(R), consisting of human fibroblasts alone. Based on product labeling and usage instructions, both products require multiple grafting procedures by physicians into the wound area (and may require the use of sutures) on a weekly or bi-weekly basis, by physicians over a 12-week period. Some products in this class require low temperature storage (-70 degrees Celsius) or need to be special ordered by a physician immediately prior to patient treatment because of a very limited shelf life (approximately 10 days).
Negative Pressure Wound Therapy - Negative pressure wound therapy for the treatment of diabetic ulcers consists of medical devices employing the use of specialized wound dressings connected to an air supply line linked to a microprocessor-controlled air pump to create a healing environment around the wound. These systems are designed to create a moist wound environment, reduce edema and promote formation and perfusion of granulation tissue. They have been proven to be safe and effective, accommodate a wide range of wound sizes, and are used in a broad range of other types of wounds including surgical as well as trauma wounds. However, effective therapy generally requires that these systems be used by patients on a 24/7 basis for up to 16 weeks (based on recently published studies). As a result, they are complex and challenging for patients to use over extended periods of time, impair patient mobility, and require repeated physician visits, equipment cleansings and dressing changes.
Wound Care Centers - Chronic wounds represent a significant unmet medical need as evidenced by the emergence and growth of wound care centers across the U.S. These centers were developed by healthcare providers to provide specialized treatment to chronic wound patients. There are an estimated 1,000 outpatient wound care centers across the U.S. Wound care centers offer a broad spectrum of specialized care as well as best clinical practices for managing wound healing. Many centers provide hyperbaric oxygen therapy and most have access to a multidisciplinary medical team. Usually associated with a hospital, these centers provide a focused approach to wound management with the goal of reducing the need for inpatient care and surgical procedures such as amputation.
Excellarate Product Candidate - Cardium's Excellarate product candidate is initially being developed to facilitate wound closure in non-healing diabetic foot ulcers. The Company believes that the ability to achieve closure of chronic, non-healing wounds following the treatment of a simple-to-use, physician administrated topical gel offers the potential for considerable benefit to patient populations with chronic diseases such as diabetes. Currently available advanced wound care products for these patients have a number of limitations such as requiring a regimen of repeated wound cleanings and product re-administrations, multiple trips to a treatment center, or custom-produced and expensive skin substitutes. In addition, many patients, including approximately one in seven participants in the MATRIX clinical study, have wounds that do not close even after previous treatment with what are regarded as the most advanced wound care therapies currently available (i.e., repeat-administration therapies using becaplermin protein or negative pressure pumps, or "living-skin" equivalents).
Market Opportunity and Pharmacoeconomics
Diabetic foot ulcers affect about 15% of the almost 24 million diabetic patients in the United States, or 3.6 million people. Each year, over 1.3 million patients in the U.S. develop diabetic foot ulcers. Of these patients, 6 percent will be hospitalized due to infection or other ulcer-related complications. The cost of diabetic ulcers to the U.S. healthcare system is approximately $5 billion per year with treatment and subsequent lower limb amputations adding an additional $1 billion per year. Diabetes is the leading cause of non-traumatic lower extremity amputations and approximately 14 to 24 percent of patients with diabetes who develop foot ulcers eventually have an amputation. The three year survival rate after amputation is only 50 percent.
Emerging trends in wound healing and a growing market demand are evidenced by the recent success of negative pressure wound therapy products, such as those marketed and sold in the U.S. by Kinetics Concepts Inc. and Smith & Nephew, representing the first $1.0 billion product segment in the wound care market. Based on these trends and needs, agents designed to accelerate the rate of wound healing are expected to play a more prominent role in the future of advanced wound care. As reported by MedTech Insight, the wound care market is projected to experience double digit growth over the next 3 to 5 years, with advanced wound care products comprising the fastest growing segment of the total wound care market. There are an estimated 91.3 million wounds in the U.S., which include 67.0 million surgical wounds, 17.6 million trauma wounds including burn injuries and amputations, 2.5 million pressure ulcers, 3.6 million diabetic ulcers and 3.3 million venous stasis and arterial ulcers. The ability to effectively address even a small proportion of these wounds would represent major new market opportunities for the Company's Gene Activated Matrix (GAM) technology.
Excellarate Phase 2b Clinical Trial Data
Earlier this week, Cardium announced that all patients enrolled in the Company's MATRIX clinical study have completed their initial 12-week evaluation period and that it plans to provide detailed safety and efficacy data around the end of September 2009. The Phase 2b MATRIX clinical trial is a prospective, randomized, double-blind, placebo-controlled study of Excellarate for the potential treatment of chronic diabetic foot ulcers. This landmark gene therapy clinical study was designed to evaluate safety and efficacy in patients receiving the Excellarate drug candidate compared to placebo controls. A standard of care reference arm was also included in the study. The safety and key efficacy measures of the MATRIX study include complete wound closure, time to complete wound closure, absolute and percent change in ulcer area, and wound healing trajectories at various time points, as well as other safety and healing metrics, which will be used to develop the planned Phase 3 clinical study. In addition, following the initial 12-week efficacy evaluation period, patients whose wounds have successfully closed will be followed for three months to further evaluate wound healing durability.
Cardium recently announced its plans to develop a DNA-based orthobiologics product portfolio based on research and development that will initially focus on non-union bone fractures for medically-compromised patients, and spinal fusions for patients with degenerative disc disease. Orthobiologics is a rapidly growing segment of the orthopedics market and represents biologically-active products designed to enhance musculo-skeletal repair and regeneration. The initial orthobiologics focus will be on the development of Osteorate(TM), a DNA-based non-surgical injectable bone graft gel to repair bone fractures and regenerate tissue in certain medically-compromised patient populations. Osteorate will be based on reformulation of Cardium's DNA-based Excellarate wound healing product candidate, which is designed to stimulate localized and sustained cellular production of platelet-derived growth factor-B (PDGF-B) protein, as a treatment for patients with non-healing diabetic foot ulcers. The Gene Activated Matrix technology allows for a broad spectrum of biocompatible matrix formulations which would include, but not be limited to, collagen, demineralized bone, allograft and synthetic graft materials.