LOS ANGELES--(BUSINESS WIRE)--CytRx Corporation (NASDAQ:CYTR - News), a biopharmaceutical company engaged in the development and commercialization of human therapeutics, today announced that iroxanadine, its next drug candidate in the pipeline believed to stimulate the normal cellular protein repair pathway through the activation of "molecular chaperones," has demonstrated the ability to dramatically and reproducibly accelerate the healing of skin wounds in diabetic animals. Based on these favorable preclinical results and earlier clinical study data, CytRx plans to move into a Phase II clinical trial with iroxanadine for the treatment of diabetic foot ulcers in the first half of 2008, subject to FDA clearance.
The animal study included a group of 10 mice genetically predisposed to diabetes (called db/db) and a second group of 10 non-diabetic sibling mice (called db/-). Each mouse received two surgical circular skin wounds to its back, which were then bandaged. As a means to quantitatively measure wound repair, study mice were monitored to determine the time required for half of the wounds to heal to closure, or the median closure time. Similar to human diabetic ulcers, the wounds healed more slowly in the diabetic animals compared with normal non-diabetic animals. In untreated diabetic mice, the median closure time was 23.5 days, significantly slower (p less than 0.0001) than the 13.6-day median closure time in the untreated non-diabetic animals.
When the diabetic mice in this study were treated daily with oral iroxanadine starting the day of wounding, healing was accelerated to a median closure time of 14.0 days, significantly better than the untreated diabetic animals (p less than 0.0001), and statistically indistinguishable from the non-diabetic animals. The wound surface area was also measured during healing for each group, again indicating a significant improvement in healing in iroxanadine-treated mice (p less than 0.005). This result is similar to results from a previous study, demonstrating that the improvement in diabetic wound healing by iroxanadine is reproducible. Iroxanadine did not accelerate wound healing in non-diabetic animals, showing that the therapeutic effect is specific for the damage that occurs due to diabetes. Furthermore, there was no detectable effect on serum glucose levels, suggesting a direct affect by the drug on the wound itself, rather than on the underlying cause of diabetic complications, high serum glucose.
"These encouraging new preclinical results with iroxanadine further substantiate the broad therapeutic potential of our molecular chaperone platform technology and suggest iroxanadine's therapeutic potential in helping patients recover from one of the more serious complications of diabetes - foot ulcers that won't heal properly," said CytRx President and CEO Steven A. Kriegsman. "If effective in human clinical trials, treatment with iroxanadine could represent a major breakthrough in quality of life for the estimated three million American patients with these ulcers, especially for the 82,000 patients each year who would otherwise suffer amputation from this debilitating condition. Iroxanadine could represent a major revenue opportunity for CytRx in a market that it is $5 billion in the US alone."
Mr. Kriegsman added, "We are now accelerating our clinical programs with three significant (one potentially pivotal, two Phase II) clinical trials expected to commence during the next 12 months, subject to FDA clearance."
Orally-administered iroxanadine was previously demonstrated to be safe and well-tolerated in two Phase I studies in healthy volunteers and in one Phase II clinical trial in patients with chronic high blood pressure. This latter clinical trial further demonstrated a significant improvement in a certain type of damage to blood vessels, called "endothelial dysfunction," which occurs in this hypertensive patient population.
"We suspected that iroxanadine might accelerate diabetic wound healing because of its previously-demonstrated ability to repair damaged endothelial cells that line the interior surface of blood vessels, a result that has been demonstrated in both human and animal studies," stated Jack Barber, Ph.D., CytRx's Chief Scientific Officer. "We believe that these cells become damaged and dysfunctional due to the accumulation of misfolded toxic proteins under adverse conditions such as high blood pressure, high serum cholesterol and diabetes. It is thought that iroxanadine works by enhancing 'molecular chaperones' to remove misfolded toxic proteins that may accumulate on endothelial cells due to the stress of diabetes." Dr. Barber added, "Based on our results to date we plan to commence a Phase II clinical trial with iroxanadine, while continuing to pursue our clinical programs with our other small molecule drug candidate arimoclomol for the treatment of ALS in the second half of this year and for stroke recovery in the first half of 2008."
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