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.
While other advanced care products for treating diabetic wounds are available, the article also observed that several aspects of those approaches can limit their use and additional new therapies are needed. As noted, "Living skin equivalents (e.g., Apligraf® and Dermagraft®) are effective in accelerating ulcer repair; however, multiple weekly applications are typically required. The usage of these products is limited due to short shelf life (5-10 days) and expense. Becaplermin (Regranex®, platelet-derived growth factor-B homodimer [PDGF-BB], Systagenix Wound Management, Gargrave, UK) is the only growth factor protein approved for use in diabetic ulcers. However, the healing incidence is only 15% greater than placebo-treated ulcers. Problems with maintenance of the protein at the ulcer site (daily application required), and for a sufficient period of time (weeks to months), have been identified as factors contributing to this low rate of efficacy [citations omitted]."
"The publication of the positive safety and open label efficacy findings of our Matrix Phase 1/2 clinical study in the peer-reviewed Wound Repair and Regeneration journal provides an opportunity for the medical community to review the significant advancements that we are making in the fields of DNA-based gene therapy and wound healing. The findings from this Phase 1/2 clinical study are consistent with and further supported by results from our much larger blinded Phase 2b clinical study as reported yesterday, which suggest that both Excellarate and its component collagen matrix known as Excellagen appear to promote wound healing at rates substantially higher than with standard of care and may have important roles as new therapeutic tools for the potential treatment of soft tissue wounds such as diabetic ulcers," reported Christopher J. Reinhard, Cardium's Chairman and Chief Executive Officer.
"Based on collective data obtained in the Phase 1/2 and Phase 2b clinical studies, and approvals related to the use of collagen in a number of clinical settings, the Company plans to advance Excellagen along an abbreviated FDA 510(k) pathway as a medical device - and to advance Excellarate to a Phase 3 clinical development program for the potential treatment of diabetic lower extremity ulcers, which are the leading cause of amputations and associated morbidity and mortality in the U.S. and other industrialized countries," Mr. Reinhard added.