Peripheral Arterial Disease (PAD)

November 7, 2011

Pluristem released long term results from two phase I trials of PLX-PAD, their placenta-based cell therapy for critical limb ischemia. The two phase I studies were conducted in the USA and Germany and enrolled 27 subjects. Twenty-two of the subjects received a single course of PLX-PAD cells injections above and below the knee of the afflicted limb. The remaining subjects received a double dose of PLX-PAD cells from the same placental source in two courses administered two weeks apart. This was done in order to test for a delayed immunological response. In the entire population, four treatment failures occurred over 12 months, resulting in an Amputation Free Survival (AFS) rate of 85.2%, compared to historical control data of 66.8% for the same time period. PLX-PAD demonstrated a safe immunologic profile at all dosage levels. The subjects who received the double dose of PLX-PAD cells did not show evidence of adverse events.

September 20, 2010

Pluristem issued positive pooled results from two parallel phase I trials evaluating PLX-PAD, placenta-derived cell therapy, for critical limb ischemia. These open-label, dose-escalation studies were performed in the U.S. and the E.U and enrolled 21 subjects who received low, intermediate and high intramuscular doses of PLX-PAD. Across all doses, 13 subjects (62%) demonstrated an improvement in the ankle-brachial index (ABI), a measure of blood flow. Eleven subjects receiving the intermediate dose demonstrated a statistically significant improvement from baseline (P≡0.033). Across all doses, 13 subjects (62%) demonstrated an improvement in the Transcutaneous Oxygen Pressure (TcPO2), a measure of tissue oxygenation. This improvement was statistically significant in the European study where the distribution of injections was higher (P≡0.05). In the combined dose groups, 17 subjects (81%) demonstrated an improvement in ABI, TBI or TcPO2. In addition, 15 subjects (71%) from all dose groups demonstrated an improvement from baseline in the reduction of pain as measured by using the VAS, with statistical significance reached in the European study (P≡0.013).

May 10, 2010

Pluristem reported positive interim top-line results from two ongoing phase I studies evaluating their placental derived stromal cell product PLX-PAD for the treatment of limb ischemia from Peripheral Artery Disease. Approximately 27 subjects with critical limb ischemia are expected to be enrolled in the two trials, underway in the U.S. and Germany. At this time, a total of 21 subjects had been enrolled and treated with one of three doses of PLX-PAD. Both trials have met their primary safety endpoints. The administration of PLX-PAD cells did not induce an immune response in any of the patients dosed, demonstrating that injection of PLX-PAD cells is well tolerated. Twelve of the 21 subjects have completed their three-month follow-up. Improvement was assessed by analyzing the hemodynamic measurements as defined in the efficacy parameters in the study protocol: ankle-brachial index, toe-brachial index and transcutaneous oxygen pressure Ten of these 12 subjects (83%) demonstrated an improvement in at least one of these parameters and 83% demonstrated an improvement in their Quality of Life.

March 1, 2010

Aastrom released positive interim results from a phase IIb trial of evaluating autologous vascular repair cells (VRCs) for the treatment of peripheral arterial disease patients with critical limb ischemia. This controlled, randomized, double-blind, multicenter trial (RESTORE-CLI) plans to enroll 150 subjects. The subjects received intramuscular injections of the VRCs or placebo into the affected limb. Interim data are from 46 subjects. The safety profile was similar between the treatment and placebo arms. Based on a composite efficacy endpoint assessing time to treatment failure, the VRCs were more effective than placebo (P<0.05). Other clinically meaningful endpoints, including major amputation rate and complete wound closure, approached but did not reach statistical significance.

June 25, 2007

AnGes announced positive results from a phase III trialof AMG0001 for the treatment of Critical Limb Ischemia (CLI).This randomized, placebo-controlled, double blind study enrolled 40 subjects inJapan. Of the subjects, 27 received AMG 0001 8mg (4mg x 2) and 13 received placebo.The primary endpoints, improvement of rest pain ((VAS (Visual Analog Scale)) orischemic ulcer size, at 12 weeks post dosing, showed statistical significance,with a 70.4% improvement in the AMG0001 group versus a 30.8% improvement in theplacebo group (p=0.014). Treatment was well tolerated, with adverse reactionssimilar between the groups. Based on the results, AnGes stopped the trial earlyto prevent potential ethical issues against the placebo group subjects. The companyplans to move forward with filing for Japanese and US approval.

December 8, 2003

Genzyme reported positive results from two phase I trials investigating an HIF-1alpha gene therapy for the treatment of critical limb ischemia. Results showed that Ad2/HIF-1alpha/VP16 was safe, with no treatment-related serious adverse events reported. The randomized, double-blind, placebo controlled study trial enrolled 28 subjects with advanced critical limb ischemia. Preliminary results were also reported from a companion open-label dose escalation trial. Three placebo subjects from the main trial received Ad2/HIF-1alpha/VP16, and 10 new subjects received Ad2/HIF-1alpha/VP16. Data showed that complete ulcer healing was observed in three of the five treated subjects, assessed at one year. Results were reported at the American Heart Association's annual meeting in Orlando.

January 27, 2003

Spectranetics reported positive results from a pivotal phase II trial investigating LACI (Laser Angioplasty Critical Limb Ischemia), an experimental device for the treatment of limb ischemia. Data showed that the primary endpoint, six-month survival with limb salvage, was achieved in 93% of treatments compared to 87% in the control group. Results showed significant adverse events in treated subjects were nearly 50% less than those of the control group. The trial enrolled 145 subjects who were poor surgical candidates at 14 U.S. and several European sites. Trial data was compared to a control group consisting of 789 subjects with critical limb ischemia treated with a variety of standard therapies.