Diffusion Pharmaceuticals LLC announced positive results of its phase I/II proof-of-concept study of Trans Sodium Crocetinate (TSC) in patients suffering from walking impairment due to Peripheral Artery Disease (PAD). The study results, presented orally to an international audience at the American Heart Association Scientific Sessions, demonstrate that TSC could improve walking ability, delay onset of leg pain and enhance overall quality of life for people with PAD. TSC is a novel small molecule drug that treats hypoxia, the lack of oxygen in tissues that underlies PAD.

“Based on these encouraging results, we are exploring opportunities with several companies to advance the development of TSC,” said David Kalergis, chief executive officer of Diffusion Pharmaceuticals. “Our goal is to bring to market a safe and effective therapy as quickly as possible, providing new hope for patients with PAD, cardiovascular disease, cancer and other conditions related to hypoxia.”

In this 48 patient study, a notable dose-response was observed for peak walking time on a graded treadmill test at several TSC dosing levels after five days of treatment. There was a clinically meaningful improvement for the patients who received 1.50 mg/kg of TSC that was nearly three times the improvement observed with the placebo group.

“PAD remains a challenging condition to treat, with an inadequate number of approved therapies. Given the dearth of successful clinical research options in PAD, these study results are exciting,” said study presenter William Hiatt, MD, professor of cardiovascular research in the Department of Medicine, University of Colorado School of Medicine; President of CPC Clinical Research and chairman of the American Heart Association’s Peripheral Vascular Disease Council.

“The magnitude of improvement that we saw with TSC after 5 days of treatment is in the range of that seen after months of therapy with a marketed product for PAD, but with a potentially superior safety profile for TSC” he exclaimed.

The phase I/II trial was a randomized, double-blinded, placebo-controlled study of TSC in patients with intermittent claudication symptoms from PAD. The study enrolled 48 patients, with 5 patients each receiving TSC at doses of 0.25, 0.50, 0.75, 1.00, 1.25, 1.50, 1.75 and 2.0 mg/kg and a placebo arm. Study medication was dosed intravenously as a bolus injection once daily for five consecutive days. Forty patients received TSC and 8 received placebo. TSC was safe and well-tolerated at all doses in this elderly PAD population. Adverse events were not predominant on any drug dose relative to placebo.

The trial was sponsored and funded by Diffusion Pharmaceuticals and conducted in collaboration with CPC Clinical Research, a not-for-profit academic research organization affiliated with the University of Colorado and specializing in the clinical testing of new approaches to the treatment of PAD. CPC is headed by Dr Hiatt.

TSC is a novel small molecule that treats hypoxia by enhancing the diffusion of oxygen selectively to oxygen-deprived tissues. TSC alters the structure of blood plasma through the creation of hydrogen bonds. More hydrogen bonds among water molecules create a less dense liquid, which enables a faster rate of oxygen diffusion.

Its ability to safely promote the movement of oxygen to hypoxic tissue has been consistently demonstrated in animal models, including haemorrhagic shock, stroke and heart attack. A 40 patient Phase-I safety clinical trial was successfully completed in 2007, with TSC well-tolerated in the study. An oral formulation of TSC is in development.

Hypoxia, the lack of oxygen in tissues, remains a challenging factor underlying many serious medical conditions with unmet treatment needs. A safe and effective treatment for hypoxia, which has thus far eluded the scientific and medical community, could address unmet medical needs in the treatment of many conditions, including Peripheral Artery Disease (PAD), cardiovascular disease, cancer, and respiratory disorders; as well as critical care uses such as trauma, haemorrhagic shock, stroke and heart attack.

PAD, which affects 10 million Americans, is a circulation problem characterized by hypoxia. The leading cause of PAD is atherosclerosis, when blood flow is restricted by the build-up of plaque, preventing blood from passing through narrowed or blocked vessels, and restricting oxygen and other nutrients from getting to normal muscle tissue. The most common symptom of PAD is claudication, leg pain that occurs when walking and disappears when the person rests.

In more severe cases of PAD, the patient may experience continuous pain, and in the most severe cases, insufficient blood flow leads to ulceration, gangrene and limb amputation. PAD is a debilitating condition whose current treatment options are often considered inadequate.

Diffusion Pharmaceuticals is a clinical-stage company developing first-in-class drugs to treat hypoxia in serious conditions with unmet medical needs. These proprietary small molecules work by a novel mechanism of action that enhances the diffusion of oxygen selectively to hypoxic tissue.