Massive Phase 3 Critical Limb Ischemia Study Funded

Critical limb ischemia (CLI) is an advanced stage of peripheral artery disease. Fatty deposits block arteries in the legs, severely reducing blood flow and causing pain, non-healing ulcers, and gangrene. Patients with CLI are at a high risk of amputation and death. Those patients unsuitable for revascularization are left with no adequate treatment options. Millions, worldwide, suffer from this ailment.

One company that has taken on the treatment challenge for CLI is Pluristem Therapeutics Inc. of Haifa, Israel. The company is a developer of placenta-based cell therapy products and is involved in a pivotal Phase III trial of its product PLX-PAD cells used to treat CLI.

The trial is currently enrolling patient-participants in the United States, the United Kingdom and Germany. Austria’s Agency for Health and Food Safety recently cleared the company’s CLI study so other Europeans may participate in the 250 patient Phase III trial. The company is hoping to have 40 active sites by the end of 2017.

Pluristem’s PLX-PAD cell therapy is one of a few therapies in the world to have been selected to take part in the European Medicines Agency’s Adaptive Pathways pilot project. The project’s goal is to streamline development for promising innovative medicines to allow for early access to patients with serious conditions who lack adequate treatment.

The Phase III trial is planned to enroll a total of 250 patients across 40 clinical sites to evaluate PLX-PAD in the treatment of CLI in a double-blind, randomized, placebo-controlled trial. The patients will all have CLI Rutherford Category 5—making them unsuitable candidates for revascularization. The patients will be injected twice intramuscularly two months apart, with 300 million cells or a placebo. The primary endpoint will be time to amputation or death.

This Phase III CLI trial has received an $8 million grant from the European Union’s Horizon 2020 program. This will cover a significant portion of the costs of the multinational trial. Following the completion of the study, data from all 250 participants will be submitted to the EMA to apply for full marketing approval in Europe and will be reviewed by the U.S. FDA for a Biologics License Application.

Zami Aberman, chairman and co-CEO of Pluristem, said, “CLI is a severely debilitating and life-threatening disease that affects tens of millions of patients around the world. Approval for this trial and its innovative time-to-event endpoint by regulatory bodies worldwide reinforces our belief that our PLX-PAD cell therapy has great potential to successfully treat these patients and enable them to lead long and healthy lives.” No tissue matching is required to administer PLX cell products.

According to Karine Kloenhaus, M.D., vice president of Pluristem’s North American office, the incidence of CLI is growing worldwide driven by ageing populations and lifestyles that result in obesity and diabetes.