Limb Preservation and Amputation

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.

June 6, 2011

Aastrom Biosciences issued results from a phase IIb trial of ixmyelocel-T, their bone marrow-derived cellular therapy for damaged tissue in a lower extremity caused by critical limb ischemia (CLI). This double-blind, placebo-controlled trial, RESTORE-CLI, enrolled 86 subjects with a diagnosis of CLI and no previous major amputations. The subjects received intramuscular injections of ixmyelocel-T or an electrolyte solution into the affected limb and were followed for 12 months after treatment. The primary endpoint was time to first occurrence of treatment failure, measured by the following components: major amputation of the treated leg, all-cause mortality, doubling of wound size from baseline, and de novo gangrene. The trial met its primary safety and efficacy endpoints, demonstrating a statistically significant improvement in the primary endpoint at 12 months.

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.

December 1, 2008

Aldagen reported positive results from a phase I/II trial of ALD-301, a stem cell therapy for the treatment of critical limb ischemia. The randomized study enrolled 21 subjects; 10 of whom received ALD-301 stem cells extracted from their own bone marrow samples, and 10 of whom received multiple injections of their own untreated bone marrow. They were subsequently monitored for up to six months. The primary objective of the trial was to evaluate the safety of ALD-301. Secondary objectives included change in clinical status from baseline to 12 weeks, as measured by the Rutherford category. ALD-301 was well tolerated. Four of the 11 subjects in the ALD-301 treatment group improved in Rutherford category and were no longer categorized as having critical limb ischemia at 12 weeks. One of the 11 subjects in the ALD-301 treatment group worsened clinically over the 24-week trial. There was a statistically significant increase in mean ankle-brachial index (ABI) in the ALD-301 treatment group at 12 weeks compared to baseline (p≡.03). There was also an increase in mean transcutaneous partial pressure of oxygen (TcPO2) in the ALD-301 treatment group at 12 weeks compared to baseline.

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.