Cardium Therapeutics (NYSE Amex: CXM) today announced the publication of positive findings from the open label multi-center Phase 1/2 clinical study of Excellarate(TM) (GAM501, Ad5PDGF-B / 2.6% collagen), its product candidate for the potential treatment of non-healing diabetic foot ulcers. The clinical findings, entitled Treatment of Nonhealing Diabetic Foot Ulcers with a Platelet-Derived Growth Factor Gene-Activated Matrix (GAM501): Results of a Phase 1/2 trial (Mulder, et al), are to be published in the October 2009 issue of Wound Repair and Regeneration, a peer-reviewed medical journal of the Wound Healing Society. The publication is now available online at the following website: http://www3.interscience.wiley.com/journal/122648469/abstract.
As reported in the article, the primary objectives of the Phase 1/2 clinical study were to evaluate the safety, maximum-tolerated dose, and preliminary biological activity of the Excellarate product candidate. The open label study evaluated fifteen patients with chronic, non-healing ulcers who were treated with local application at the wound site of either a single administration of the Excellarate product candidate at one of three dose levels, or up to four administrations of Excellarate at one-week intervals.
The principal findings of the Phase 1/2 clinical study as reported in the article include the following:
- Excellarate appeared to be both safe and well tolerated following administration in patients with non-healing diabetic ulcers, with no evidence of systemic or local toxicity at any dose level (therefore no maximum-tolerated dose was reached);
- Ad5PDGF-B and the collagen matrix of Excellarate, as well as the encoded PDGF-B protein, appeared to remain localized within the wound site (as evidenced by an absence of circulating adenoviral DNA, and the absence of any detectable antibodies to either the encoded PDGF-B protein or the collagen in the blood of patients);
- Complete wound closure was observed by 14 weeks in ten of the fifteen patients (67%), seven of whom had received only a single application of the Excellarate product candidate; and
- 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).
The Excellarate product candidate (referred to as GAM501 in the article) is initially being developed to facilitate wound closure in non-healing diabetic foot ulcers. Excellarate is a collagen-based topical gel employing Cardium's Gene Activated Matrix(TM) technology to locally stimulate the release of platelet-derived growth factor-B protein (PDGF-B) and provide a matrix for cell migration, which are believed to be important keys in the human body's wound healing process. The sustained localized production of PDGF-B by a patient's own cells directly in 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. Cardium's customized collagen matrix (Excellagen(TM)), which forms an integral part of the Excellarate product, is believed to support the process of wound healing by promoting retention of Ad5PDGF-B and the encoded PDGF-B protein within the wound site, and also serves as a scaffold to support the infiltration and proliferation of wound repair cells. These activities are considered to be important for the effective stimulation of a variety of wound healing processes.