Pluristem Therapeutics Inc. reported that data from clinical trials show the company’s placenta-derived cell therapy, PLX-PAD, is safe and improves quality of life as well as other efficacy measurements in patients with Critical Limb Ischemia (CLI), the end-stage of Peripheral Artery Disease (PAD).

The three-month follow-up data involved 21 patients afflicted with CLI in two open-label, dose-escalation, phase I clinical trials conducted at Duke University Medical Center, Stanford University Medical Center, the Center for Therapeutic Angiogenesis in Birmingham, Alabama and St. Franziskus Hospital, supported by the Charité - University Medicine Berlin. The results of these clinical trials have enabled Pluristem to select the target treatment dose of PLX-PAD for additional studies focused on the cell therapy’s efficacy. Pluristem has communicated with both the US Food and Drug Administration (FDA) and European Medicines Agency (EMA) concerning the design of an optimal multinational study that will support an approval for marketing PLX-PAD for the treatment of CLI.

The two phase I studies were designed to evaluate the safety of PLX-PAD cells and included accessing the patient’s immunological profile before and after the local administration of PLX-PAD. In addition, efficacy parameters were assessed and five different doses of PLX-PAD were evaluated. These studies were performed in parallel in the EU and USA and represent the first time that Pluristem’s PLX-PAD cells were administered to humans. PLX-PAD cells are derived from human placenta, a non-controversial, non-embryonic, adult stem cell source.

Results included the findings that PLX-PAD cells can be administered safely as an “off-the-shelf” product without a need for matching between donor and patient. Additionally, efficacy was demonstrated across all doses with a statistically significant improvement noted in the pain score and quality of life. The intermediate dose also showed a statistically significant improvement in the Ankle Brachial Index (ABI), a measure of blood flow.

Edwin M Horwitz, MD, PhD, chairman of Pluristem's Scientific Advisory Board, President of the ISCT (International Society of Cell Therapy) and Director of Cell Therapy in the Division of Oncology / Blood & Marrow Transplantation at Children’s Hospital of Philadelphia stated: “Interestingly, the statistically significant improvement in the symptom of pain as measured by the Visual Analogue Score (VAS) suggests PLX cells may be effective therapy for other pain syndromes, such as the neuropathic pain associated with Herpes Zoster (shingles). Neuropathic pain includes an ischemic and inflammatory etiology. The previous announcement that PLX cells significantly improved the outcome in two different animal models of neuropathic pain, in addition to the significant VAS improvement in this study, suggests PLX cells may also be used as a potential pain therapy”.

Safety Endpoints: No significant unfavourable effects due to the administration of PLX-PAD occurred. One major amputation was reported in the PLX-PAD high dose group and was determined not to be related to the administration of PLX-PAD cells. This case represented 4.7 per cent of all patients treated in this study and compares to historical data that indicates a 35-40 per cent major amputation rate in CLI patients/yr.

None of the patients developed an anti-HLA antibody response and no specific anti-PLX HLA class-I or class-II antibodies were detected in the patients tested. This indicates PLX-PAD cells are immune competent and can be given to the patient “off-the-shelf” without a need for matching.

Immunological profiles demonstrated a rise in anti-inflammatory and angiogenic protein secretion post-dosing suggesting PLX-PAD cells function to deliver appropriate therapeutics proteins in response to the ischemic, inflammatory process of CLI.

Efficacy Parameters: Across all doses, 13 patients (62 per cent) demonstrated an improvement in the ankle-brachial index (ABI), a measure of blood flow. Eleven patients receiving the intermediate dose demonstrated a statistically significant improvement from baseline (P=0.033).

Across all doses, 13 patients (62 per cent) 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).

Across all doses, 17 patients (81 per cent) demonstrated an improvement in ABI, TBI or TcPO2.

Across all doses, 17 patients (81 per cent) demonstrated a statistically significant improvement from baseline in the King’s College Score for Quality of Life (QoL) assessment (P< 0.001). Eleven patients receiving the intermediate doses demonstrated the best improvement from baseline in the QoL score (P< 0.001).

Across all doses, 15 patients (71 per cent) demonstrated an improvement from baseline in the reduction of pain as measured by using the VAS. This improvement was statistically significant in the European study where the distribution of injections was higher (P=0.013).

“The results of these trials provide a strong indication of the potential success of commercializing PLX-PAD,” said Zami Aberman, president, chairman and CEO of Pluristem. “We have proven our PLX-PAD cells are safe and well tolerated when given intramuscularly as an allogeneic, “off-the-shelf” product that can be given without the need for matching between the donor and the patient. Additionally, Pluristem has been able to choose the appropriate dose of PLX-PAD to move commercialization of the product forward”.

Pluristem is a clinical stage biotechnology company with patented technology for the development and manufacturing of standardized cell therapies derived from the human placenta.