Tissue Engineering Technology: Product Programs
Excellarate | Matrix Phase 2B Excellarate Clinical Study | Phase 1/2 Excellarate Clinical Study | Excellagen | MedPodium
Excellarate
Gene Activated Matrix (GAM) Technology
The Excellarate™ product candidate is initially being developed to facilitate wound closure in non-healing diabetic foot ulcers. 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.
Excellarate is a collagen-based topical gel employing TRC’s Gene Activated Matrix™ technology 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.
The Excellarate product candidate is designed to provide physicians and patients with a potentially simpler, easy-to-use treatment regimen compared to most diabetic wound healing agents or devices in use that require repeated administrations over a long term (weeks to months). Based on recently announced advancements, Excellarate will be re-formulated as an easy-to-use single syringe that is pre-mixed and ready to be applied to patients’ wounds. The reformulation will allow Excellarate to be maintained in a physician’s office using a standard refrigerator (at a temperature of about 4°C) and is expected to have a shelf life of 15-18 months.
MATRIX Phase 2b Excellarate Clinical Study
Product Development Pathway
Based on Matrix Clinical Studies
The Company recently reported data from the multi-center Matrix Phase 2b clinical trial of Excellarate™ for the potential treatment of patients with chronic non-healing diabetic foot ulcers. The study evaluated patients treated with the Excellarate product candidate (combination of Ad5PDGF-B and 2.6% collagen) or 2.6% collagen alone compared to patient who received only the protocol specified standard of care. Nearly half of patients (48%) receiving a one-time Excellarate treatment had complete wound closure by 12 weeks, compared to a 31% wound closure rate for standard of care. Among combined one and two dose groups of Excellarate approximately 41% of patients achieved complete closure by 12 weeks. In addition to overall wound closures by 12 weeks, the Phase 2b study also evaluated wound closure rates and trajectories following product administration in order to assess the timing and extent of bioactivity. The data revealed that patients receiving Excellarate exhibited early and rapid wound healing responses as evidenced by substantial reductions in wound radius over the first several weeks following product administration, which responses were both greater and faster than those observed among patients that had received standard of care. For example, a 108% relative improvement (decrease in ulcer radius) compared to standard of care was observed over the first week following administration of Excellarate, and a 50% relative improvement was observed as an average over the first four weeks.
Phase 2b Excellarate Patient Photos
Before Treatment
After Treatment
Patient #1: This patient is a 60-year old male with a non-healing diabetic foot ulcer that had been unsuccessfully treated for five years before enrolling in the Excellarate MATRIX Phase 2b clinical study.
Before Treatment
After Treatment
Patient #2: This patient is a 70 year old female with a non-healing diabetic foot ulcer that had been unsuccessfully treated for five years before enrolling in the Excellarate Matrix Phase 2b clinical study.
Before Treatment
After Treatment
Patient #3: This patient is a 62 year old male with a non-healing diabetic foot ulcer that had been unsuccessfully treated for 12 weeks before enrolling in the Excellarate Matrix Phase 2b clinical study.
Phase 1/2 Excellarate Clinical Study
Excellarate has been studied in a Phase 1/2 clinical trial that evaluated safety and included a preliminary assessment of healing. The positive findings of this open label multi-center Phase 1/2 Excellarate clinical study were published in the November-December 2009 issue of Wound Repair and Regeneration, a peer-reviewed journal of the Wound Healing Society. The principal findings of the study concluded that Excellarate appeared to be both safe and well tolerated and that complete wound closure was observed at 14 weeks in 10 of the 15 patients (67%), seven of whom had received only a single application of the Excellarate product candidate. In addition, Excellarate appeared to be associated with early rapid healing responses (around half of the patients achieved a 50-99% reduction in wound size by week 2).
Excellagen
Excellagen™ is an advanced wound care device composed of highly-refined, soluble bovine dermal collagen (Type I), which is modified to reduce immunogenicity and promote its usefulness in wound settings. Excellagen is designed for use by health care professionals in patients with dermal wounds, which can include diabetic ulcers, pressure ulcers, venous ulcers, tunneled/undermined wounds, surgical and trauma wounds, second degree burns, and other types of wounds. In December 2009, the Company filed a 510(k) premarket notification with the U.S. Food and Drug Administration (FDA) seeking marketing clearance of its Excellagen product candidate based on positive data from the Company’s recently completed Phase 2b clinical trial that demonstrated substantial improvements in wound healing responses in patients with non-healing diabetic foot ulcers following one or two applications of Excellagen. ExcellagenXL is designed for use by health care professionals in a clinical setting and as an adjunct to standard of care topical wound therapy, which in the case of diabetic ulcers typically includes surgical debridement and off-loading. The ExcellagenFX kit is designed for use by health care providers in a clinical setting for the treatment of larger soft tissue or tunneling wounds that may occur with pressure, venous and diabetic ulcers, and surgical wounds. The ExcellagenFX flowable matrix product allows for deeper administration and direct intimate contact with the wound bed in more complex, irregular and difficult to access wounds. Other categories of advanced wound care products are manufactured with alginates, hydrogels and hydrocolloids in structured, membrane or granular product configurations, or require hydration, mixing and reconstitution immediately prior to patient administration. The Company’s Excellagen fibrillar collagen protein gel is a physiologic formulation consisting of a bioactive and biodegradable material that promotes effective wound management by providing a moist protective barrier and stimulates the natural wound healing process through the promotion of cell migration and capillary in-growth to support tissue regeneration. The Company plans to develop additional new product opportunities by incorporating other agents into Excellagen formulations, including antimicrobials, DNA and/or other biologics, which are designed to address particular wound healing and other tissue repair applications.
MedPodium
Cardium’s MedPodium™ product line is an over-the-counter advanced skin care product portfolio for patients with the potential for foot disorders and ailments. The MedPodium product line is designed to promote foot health and comfort and support preventative care, self examination and early detection of foot ulcers, especially for diabetic patients with lower extremity neuropathy. The commercial development of Cardium’s MedPodium patient care product line is intended to provide a first line of defense for individuals at risk for foot ulcers and enhances and expands Cardium’s product portfolio beyond the current Excellagen product candidate platform. The MedPodium product line will initially carry six products and have been formulated to include blended natural and botanical ingredients, and contain no artificial colors and fragrances. The various products contain exfoliants to promote the release of dead skin cells and stimulate the production of new skin cells, natural vitamin antioxidants, certain natural medicinals to aid in circulation as well as other nutrient-rich ingredients to promote soft and supple skin. Click here to view the MedPodium advanced skin care product line brochure.