Pluristem Therapeutics Inc. (Nasdaq:PSTI) (TASE:PSTI) announced on 6/12/2018 positive top-line results from its multinational Phase II clinical study of PLX-PAD cells in the treatment of Intermittent Claudication (IC). PLX-PAD treatment reduced Incidence of revascularization and improved patients’ mobility. Study results also validate the design of Pluristem’s ongoing Pivotal Phase III study in CLI, a more severe stage of peripheral arterial disease (PAD) and confirm Pluristem’s proprietary Bio-Therapeutic approach.
Pluristem's Phase II IC study was designed to evaluate the safety, efficacy and optimal dosing regimen for PLX-PAD cells in patients with IC, Rutherford categories 2-3. Enrollment took place at 28 clinical sites in the U.S., Germany, South Korea and Israel. The 172 patients in the study were randomized into four treatment groups: two administrations of 300 million PLX-PAD cells (“main efficacy group”); two administrations of 150 million PLX-PAD cells; two administrations of placebo; or one administration of 300 million PLX-PAD cells followed by placebo. In each of these study arms, the two administrations were given intramuscularly (IM), 3 months apart. The primary efficacy endpoint was the change from baseline in maximal walking distance (MWD) at 52 weeks compared to placebo. The key secondary endpoint was the change from baseline in MWD at 52 weeks compared to placebo, in patients treated with 2 doses of PLX-PAD originating from different placentas (Pluristem’s proprietary Bio-Therapeutic approach). Other endpoints included risk of revascularization and other hemodynamic and clinical outcome measures.
Top Line Results:
Patients treated with 2 administrations of 300 million PLX-PAD cells showed statistically significant improvement (p=0.0008) in MWD as compared to baseline at 52 weeks.
Key primary efficacy endpoint, improvement in MWD as compared to placebo, in analysis by country, showed best results with statistically significant improvement (effect size= 51.1%, p=0.015) in U.S patients (n=73) treated with 2 administrations of 300 million PLX-PAD cells.
Key secondary efficacy endpoint, improvement in MWD following administration of 2 doses of 300 million PLX-PAD cells originating from different placentas, showed statistically significant improvement at 52 weeks (effect size= 42.0%, p=0.043) as compared to placebo. These patients also demonstrated a statistically significant improvement (effect size= 83%, p=0.0007) in MWD at 52 weeks as compared to baseline.
Revascularization risk was reduced by 49% (Hazard ratio = 0.51) in the main efficacy group at week 65. Patients receiving 2 administrations of PLX-PAD cells originating from different placentas were “revasc-free” (no revascularization events) at week 65.
IM administration of PLX-PAD cells was safe and well tolerated.
Validation of study design in ongoing Pivotal Phase III study in Critical Limb Ischemia (CLI):
Dose confirmation- Study results demonstrated dose of 300 million PLX-PAD cells as the optimal dose for treatment of PAD
Two administrations of 300 million PLX-PAD cells demonstrated a statistically significant superior effect (p=0.0331) compared to a single administration of 300 million PLX-PAD cells in MWD at week 52, suggesting that in chronic indications such as PAD a second treatment may be required to significantly improve the clinical outcome.
Pluristem’s proprietary Bio-Therapeutic approach of using cells originating from different placentas for each administration, as implemented in the CLI pivotal Phase III clinical study, was shown to generate a superior therapeutic effect.
“We are highly encouraged by the results seen in the study. The option of treating peripheral artery diseases like IC and CLI through IM injections of PLX-PAD cells is promising, and an important outcome, demonstrating the potential ability to implement regenerative medicine advanced technologies in cardiovascular diseases. We look forward to the CLI pivotal study results that may demonstrate the ability of Pluristem’s cell therapy to improve patient outcomes and create economic benefits for the healthcare systems,” stated Dr. Manesh Patel, Chief of the Division of Cardiology at Duke University Health System, and the lead principle investigator (PI) for the U.S. Phase II IC study.
PLX cell products release a range of therapeutic proteins in response to inflammation, ischemia, muscle trauma, hematological disorders, and radiation damage. The cells are grown using the Company's proprietary three-dimensional expansion technology and can be administered to patients off-the-shelf, without tissue matching.