Date: 2011-11-03
Type of information:
phase: 1
Announcement: results
Company: Pluristem Therapeutic (Israel)
Product: PLX-PAD cells
Action
mechanism: The company's patented PLX (PLacental eXpanded) cells drug delivery platform releases a cocktail of therapeutic proteins in response to a variety of local and systemic inflammatory diseases. PLX cells are grown using the company’s proprietary 3D micro-environmental technology and are an off-the-shelf product that requires no tissue matching or immune-suppression treatment prior to administration. The PLX-PAD comprehensive clinical development plan has been recognized by both the EMA and FDA, targeting a sub-population of 20 million patients in the Peripheral Artery Disease (PAD) market.
Disease: Critical Limb Ischemia
Therapeutic area: Cardiovascular diseases
Country: USA Germany
Trial
details: Two Phase I clinical studies were conducted in the USA and Germany in accordance with protocols approved by the FDA and the PEI, respectively. Twenty-seven CLI patients were treated with PLX-PAD cells and followed for 12 months following the administration of the initial doses in the USA and for 24 months in Germany. During the clinical follow up period patients underwent clinical examinations, blood flow measurements, scores for quality of life and pain, ECGs and peripheral blood samples were drawn during their follow up visits for chemistry and immunological analysis. Twenty-two of the twenty seven patients in the US and Germany received a single course of PLX-PAD cells with either 30 or 50 IM injections above and below the knee of the afflicted limb in a treatment that took, on average, approximately 20 minutes to complete. The remaining five US patients received a double dose of PLX-PAD cells in two courses administered two weeks apart. These five patients received both courses of PLX-PAD cells from the same placental batch. This was done in order to test for a delayed immunological response. Three dosage levels of 200, 300 and 600 million PLX-PAD cells were evaluated. The five patients treated with the double dose of PLX-PAD cells received each a total dose of 600 million PLX-PAD cells [Dose variance equals +/- 10%].
Latest
news: * On November 3, 2011, Pluristem Therapeutics has announced positive 12-month data from its Phase I open-label, dose-escalation clinical trials conducted under protocols approved by the FDA in the USA and the Paul-Ehrlich-Institute (PEI) in Germany. PLX-PAD cells met all the clinical studies’ protocol endpoints, demonstrating a safe immunologic profile at all dosage levels and found to be potentially effective in treating patients suffering from Critical Limb Ischemia (CLI). The endpoints of these Phase I trials included data on tumorigenesis, adverse events, immunological reactions, laboratory and ECG findings. The results of these two trials are combined for reporting purposes. No malignancies were reported and all serum sample levels of tumor markers (PSA, CEA, CA125, AFF and NSE) were within normal range for all patients tested. Monitoring for malignancies was required only in the clinical trial conducted in Germany. It was concluded that treatment with PLX-PAD cells does not induce tumorigenesis. No clinical evidence of adverse events or toxicities related to the intramuscular (IM) administration of PLX-PAD cells was observed in twenty-six of twenty-seven patients. Only one patient in the US trial experienced a transient local cutaneous inflammation after PLX-PAD was administered. A transient change was noted in the leukocyte and lymphocyte count in the patients, which returned to pre-injection baseline levels within 7 days and without evidence of absolute lymphopenia. No ECG abnormalities were detected during the treatment and monitoring periods. Additionally, five of the twenty-seven patients received a double dose of PLX-PAD cells from the same placental batch two weeks apart without evidence of adverse events.
Table 1: Cumulative Event Rate Comparison
Based on the above data it was concluded there were no significant safety issues and PLX-PAD cells can be safely given IM to patients without matching, even if the patients are dosed twice from the same placental source. According to the study protocols, the clinical follow up was completed 3 months after the administration of PLX-PAD cells. During that time, statistically significant improvements were noted for the following efficacy parameters - Ankle-Brachial Index (ABI) - a measure of blood flow (P=0.033). - Transcutaneous Oxygen Pressure (TcPO2) - a measure of tissue oxygenation (P=0.05) - Quality of Life (QoL) - (P< 0.001) - Visual Analogue Score (VAS) – a measure of pain (P=0.013) The European Medical Agencies (EMA) and the FDA require the primary endpoint for CLI pivotal clinical trials to be Amputation Free Survival (AFS) rate. AFS data was collected during the Phase I studies and compared with another published CLI trial's data. From a total of twenty-seven patients, four treatment failures occurred during the observation period of twelve months, which resulted in an AFS rate of 85.2%, as opposed to historical control data of 66.8% for the same time period. This corresponded to an event rate of 14.8%, as opposed to historical control data showing a 33.2% event rate, as outlined in Table 1 below. Therefore, based on the endpoint of AFS at 12 months, it was concluded there is a trend towards efficacy of PLX-PAD cells in the treatment of CLI.
* On April 13, 2011, Pluristem Therapeutic has announced that following completion of three and six month clinical follow-up, data from its two open-label, dose-escalation, Phase I clinical trials conducted in the US and Germany suggests that its placenta-derived cell therapy, PLX-PAD, is safe, improves quality of life, and is potentially effective in treating patients and reducing amputations in those suffering from Critical Limb Ischemia (CLI), the end-stage of Peripheral Artery Disease (PAD). Among the 27 patients treated with PLX-PAD, only one amputation was recorded, representing a 3.7% amputation rate. This represents a 75% reduction in amputation rate compared to historical data, which varies from 20-40%.
Full results of Pluristem's clinical trials are expected to be published in a peer-reviewed journal within the next few months.
