Cesca Therapeutics Amends IDE Application for Critical Limb Ischemia Treatment Study

Rancho Cordova, Calif.-based Cesca Therapeutics Inc., an autologous cell-based regenerative medicine company, has submitted its amendment to the investigational device exemption (IDE) application to the U.S. Food and Drug Administration (FDA) for a U.S. pivotal multicenter study of the company’s Surgwerks-CLI and VXP system for treating advanced stages of no-option lower limb critical limb ischemia (CLI). The amendment outlines the company’s responses to the FDA’s deficiencies in the original pivotal application. The amendment includes considerable data specific to assessing the Surgwerks-CLI and VXP system autologous cellular output and new methods in assessing the rapid device output in the operating room. The company also notes that it has filed additional intellectual property as a result of this new work.

“This proposed pivotal trial is an important step toward the development of an autologous cell-based treatment for no-option critical limb ischemia patients,” said Ken Harris, Cesca’s president and head of clinical development. “The novel approach developed and outlined to the FDA combines the best of the consistency of manufactured cell therapies with the safety of autologous cells. Essentially, we have now taken the cell manufacturing plant with its quality department and miniaturized it to be completed in the operating room in 90-120 minutes.”

The CLIRST III study will be a randomized controlled trial evaluating the efficacy of the Surgwerks-CLI and VXP system in CLI patients with non-healing foot ulcers who have no further surgical options except a major amputation versus a blinded placebo control of the same population. The primary endpoint is major amputation free survival at 12 months following enrollment and there will be an interim analysis for futility or repowering (adding more subjects) if necessary. The study will be conducted at up to 60 centers in the United States under Richard Powell, M.D., chief of vascular surgery at Dartmouth-Hitchock Medical Center and professor of surgery and radiology at Dartmouth School of Medicine. Currently, the company has nearly 40 sites in the pipeline and is using its in-house clinical research organization to properly qualify the sites to specifications of the trial.

CLI, the most severe and deadly form of peripheral arterial disease, currently affects up to 2 million people in the U.S., many of whom are in a later stage of disease progression. By 2020, the prevalence of CLI in the U.S. is forecasted to grow to as much as 3.5 million people. In the U.S., it is estimated that there are approximately 280 amputations per million people per year and that 25 porcent of all patients who undergo amputation below the knee will fail rehabilitation and require chronic institutional care or professional assistance at home. Consequently, the median cost of managing a patient after amputation is estimated to be two-three times that of successful limb salvage. Beyond the physical disability and financial cost, there is a significant emotional toll on the patient and the patient’s caregiver/family as well; psychological testing of patients with CLI shows quality of life indices similar to patients with terminal malignancy. Thus there is an absolute critical need to develop novel strategies to promote limb salvage or limb amputation delay in patients with late stage CLI with no further options for conventional revascularization. Based on this prevalence data in the United States as well as similar data for European and Asian regions, the annual economic cost of CLI related amputations is estimated at $25 billion. It is in this therapeutic arena that Cesca expects to make a significant difference in the lives of patients with this debilitating disease.