Positive Findings from Excellarate(TM) Phase 1/2 Clinical Study Published in Journal of Wound Repair and Regeneration
October 15 2009 - 8:00AM
PR Newswire (US)
SAN DIEGO, Oct. 15 /PRNewswire-FirstCall/ -- 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.
(Logo: http://www.newscom.com/cgi-bin/prnh/20051018/CARDIUMLOGO) 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. Findings of the
Phase 1/2 Excellarate Clinical Study The Phase 1/2 study was a
multi-center, open label, dose-escalation study. Fifteen patients
with previously non-healing foot ulcers were enrolled and received
either a single dose of Excellarate or up to four administrations
of Excellarate at one-week intervals and were then evaluated for up
to seven months. In addition to the application of Excellarate,
patients also followed a standard of care treatment regimen for the
entire treatment and evaluation period. Standard of care consisted
of surgical debridement, dressing changes and use of an off-loading
device. The mean size of ulcers at treatment was 3.0 +/-1.8 cm2
(range 1.17 - 7.2 cm2), and these ulcers were considered chronic,
having remained unhealed prior to treatment for a mean of 76 weeks
(range 8 - 284 weeks). In this study, 10 of the 15 patients (67%)
achieved ulcer closure during the study period with two additional
patients achieving at least a 50-99% decrease in ulcer area. The
onset of response was rapid with 7 of 15 (47%) patients achieving a
50-99% decrease in ulcer area by week 2, and 9 of 15 (60%) patients
achieving a 50-99% decrease in ulcer area by week 6. Overall, most
of the patients (93%) had a positive response, as assessed by
decreases in ulcer size. The chronic non-healing nature of these
diabetic ulcers prior to treatment and comparison of the healing
response for Excellarate-treated ulcers with the previously
published healing incidence in standard of care trials of 24% at 12
weeks, support a potential biological effect of Excellarate in
promoting wound healing. The researchers concluded that "the
potential benefits from a single (or double) administration of
GAM501 [Excellarate] could one day offer medical practitioners and
their diabetic patients an important new treatment option having a
higher degree of therapeutic efficacy than SOC (standard of care),
and a simplified treatment regimen compared with other advanced
therapies that require strict patient compliance for prolonged
periods of time. Such a new treatment option could thereby provide
a better daily quality of life and perhaps reduce amputations for
patients suffering from chronic diabetic foot ulcers." The
Excellarate clinical development program is focused on developing
new and innovative ways to enhance the treatment of diabetic foot
ulcers, which affect about 15% of the almost 24 million diabetic
patients in the United States, or 3.6 million people. Each year,
over 800,000 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. Gene Activated Matrix Technology
Platform Cardium's proprietary Gene Activated Matrix(TM) technology
platform is designed to provide a therapeutic level of protein
synthesis at a specific site in the body and can be used in soft
tissue such as skin, ligament, tendons and cartilage, as well as in
hard tissue such as bone. The technology is distinctive in that it
is immobilized gene delivery that allows for gene uptake restricted
to the application site. The Gene Activated Matrix comprises any
biocompatible matrix containing a gene or DNA vector encoding for a
growth factor or any therapeutic protein. The technology allows for
a broad spectrum of formulations and the use of any biocompatible
matrix, natural or synthetic, which would include, but not be
limited to, collagen, de-mineralized bone, allograft and other
synthetic graft materials. The Company's studies have shown that
proliferative cells migrate into the Gene Activated Matrix and then
take up the immobilized gene resulting in localized and sustained
production of small but physiologically active quantities of growth
factor proteins or other therapeutic proteins based on the
protein-producing DNA of choice. Compared with current protein
therapy, which may be limited due to the inherently short half-life
of proteins, the Company believes that the localized and sustained
production of therapeutically significant concentrations of
DNA-driven proteins at the delivery site can significantly enhance
the stimulation of localized therapeutic processes such as tissue
repair. About Cardium Cardium is focused on the acquisition and
strategic development of new and innovative bio-medical product
opportunities and businesses that have the potential to address
significant unmet medical needs and definable pathways to
commercialization, partnering and other economic monetizations.
Cardium's investment portfolio includes the Tissue Repair Company
and Cardium Biologics, medical technology companies primarily
focused on the development of innovative therapeutic products for
wound healing, bone repair, and cardiovascular indications. In July
2009, Cardium completed the sale of its InnerCool Therapies medical
device business to Royal Philips Electronics, the first asset
monetization from the Company's biomedical investment portfolio.
News from Cardium is located at http://www.cardiumthx.com/.
Forward-Looking Statements Except for statements of historical
fact, the matters discussed in this press release are forward
looking and reflect numerous assumptions and involve a variety of
risks and uncertainties, many of which are beyond our control and
may cause actual results to differ materially from stated
expectations. For example, there can be no assurance that
Excellarate or our other candidates will prove to be sufficiently
safe and effective, or that results or trends observed in one
clinical study or procedure will be reproduced in subsequent
studies or procedures, or that clinical studies even if successful
will lead to product advancement or partnering; that the
Excellarate product candidate offers the potential for simpler or
more cost-effective treatment for physicians and patients than
other FDA-approved products that currently are or will be on the
market; that the Matrix clinical study program or other human
clinical trials can be conducted and completed in an efficient and
successful manner; that we can develop a DNA-based orthobiologics
product portfolio; that our products or product candidates will not
be unfavorably compared to competitive products that may be
regarded as safer, more effective, easier to use or less expensive;
that FDA or other regulatory clearances or other certifications, or
other commercialization efforts will be successful or will
effectively enhance our businesses or their market value; that our
products or product candidates will prove to be sufficiently safe
and effective after introduction into a broader patient population;
or that third parties on whom we depend will perform as
anticipated. Actual results may also differ substantially from
those described in or contemplated by this press release due to
risks and uncertainties that exist in our operations and business
environment, including, without limitation, risks and uncertainties
that are inherent in the development of complex biologics and in
the conduct of human clinical trials, including the timing, costs
and outcomes of such trials, our ability to obtain necessary
funding, regulatory approvals and expected qualifications, our
dependence upon proprietary technology, our history of operating
losses and accumulated deficits, our reliance on collaborative
relationships and critical personnel, and current and future
competition, as well as other risks described from time to time in
filings we make with the Securities and Exchange Commission. We
undertake no obligation to release publicly the results of any
revisions to these forward-looking statements to reflect events or
circumstances arising after the date hereof. Copyright 2009 Cardium
Therapeutics, Inc. All rights reserved. For Terms of Use Privacy
Policy, please visit http://www.cardiumthx.com/. Cardium
Therapeutics(TM) and Generx® are trademarks of Cardium
Therapeutics, Inc. Tissue Repair(TM), Gene Activated Matrix(TM),
GAM(TM), Excellagen(TM), Excellarate(TM) and Osteorate(TM) are
trademarks of Tissue Repair Company.
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http://photoarchive.ap.org/ DATASOURCE: Cardium Therapeutics
CONTACT: Bonnie Ortega, Director, Investor/Public Relations,
Cardium Therapeutics, Inc., +1-858-436-1018, Web Site:
http://www.cardiumthx.com/
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