Cesca Therapeutics Inc. (Nasdaq: KOOL) is a leader in the development and manufacture of automated blood and bone marrow processing systems that enable the separation, processing and preservation of cell and tissue therapy products and generates revenues of over $16 million from the sale of these products each year.
Early last year, the Company reported exceptional early clinical trial results for treating critical limb ischemia (CLI). The company is also developing a pipeline of treatments for acute myocardial infarction (AMI), ischemic stroke, bone marrow transplant, avascular necrosis, and non-union fractures.
Over 20,000 patients have been treated using cell therapies derived from the use of Cesca’s proprietary devices and approximately 650 patients have been treated using experimental cellular therapeutics in clinical trials being developed by the Company across 8 clinical indications.
Cesca Therapeutics is the exclusive Regenerative Medicine provider to Fortis Healthcare, the largest private healthcare company in Asia with more than 10,000 inpatient beds and clinics seeing upwards of 15,000 outpatients daily. The partnership with Fortis has allowed the company to build an embedded clinical research organization with lower operating cost and global capability and expertise inside the new flagship Fortis Memorial Research Institute. Cesca also provides advanced personalized cellular medicine to Fortis’ vast network of more than 1,200 clinicians.
Cesca CLI Trial Results
Armed with very strong results from Cesca’s CLI Phase Ib trial, the company recently submitted an Investigational Device Exemption (IDE) pivotal trial (Phase III) application to the FDA for treating “no-option” lower limb critical limb ischemia. “No option”, typically assigned to late-stage disease, means the CLI patient has no further surgical options other than amputation to overcome ischemic wounds. The IDE pathway, which the U.S. Food and Drug Adminstration has determined is applicable to Cesca, in contrast to the Investigational New Drug (IND) pathway, can save significant time and money in the clinical trial process. Cesca’s current approach in advancing to a late stage development therapy is the result of not only two promising prior studies but also helpful feedback from the FDA both during a pre-IDE guidance meeting and subsequent decisions and in their IDE application response letter.
The CLI Problem
The Sage Group, a leading research and consulting think tank firm focused on Peripheral Arterial Disease and Critical Limb Ischemia, reports:
- In the U.S. the direct cost of Critical Limb Ischemia amputations is $25 billion per year
- In 2010 between 2.8 and 3.5 million U.S. citizens suffered from critical limb ischemia http://thesagegroup.us/pages/news/cli-us-10.php
- Within 5 years of diagnosis, approximately 70% of CLI patients die. This mortality rate exceeds that of coronary artery disease, breast cancer and colorectal cancer.
- 70,000 major amputations (above the ankle) and 134,000 minor amputations (toes and feet) are completed on CLI patients each year in the U.S.
- Amputation is frequently and unfortunately the only treatment that many CLI patients undergo. Recent research has shown that 60%-71% of the major amputations are performed without any attempt at revascularization.
- Between 1.1 and 2.0 million CLI patients are currently classified as “No option”.
- Average inpatient charges for CLI are $55,000—twice as high as those for stroke and almost $1,000 more than for heart attack.
Mary Yost, President of the Sage Group says, “These patients might be candidates for stem cell therapies or other new biotechnology products.”
CLI Trial Results
The company has sponsored two CLI clinical trials to date in India and in Europe. In the most recent study, Cesca Therapeutics announced in January 2014 the results from its Phase Ib Clinical Trial for CLI using its Critical Limb Ischemia Rapid Stem Cell Therapy (CLIRST) treatment. Seventeen “no option” CLI patients were enrolled in the open label study with all 17 patients recommended for amputation. After 12 months the following results were reported: http://cescatherapeutics.com/wp-content/uploads/2014/01/012114-CLI-PhIb-PRMP-Final.pdf
- Limb and Life Salvage: Major limb Amputation free survival rates were 82.4% analyzed per the protocol and greater than 70% in the Intent-to-Treat analysis
- Pain Reduction: On a scale of 0 to 10, pain was reduced from 7.8 to 0.9
- Walking Improvement: Six minute walking distance increased from 14.5 meters to 157 meters
- Wound Healing: 11 patients had gangrene with or without ulceration pre-treatment, and all of this sub-population of patients had neither gangrene nor ulceration at 12 month follow-up
- Revascularization: Advanced imaging confirmed statistically significant Vasculogenesis occurred in certain regions of the leg as a result of the treatment compared to pre-treatment levels. Blood vessels in the afflicted leg created new vessels, supporting reperfusion.
Safety: No serious adverse side effects directly related to the treatment were reported
The open label 17-patient study was conducted at the Fortis Escorts Heart Institute in New Delhi, voted best Indian cardiac facility in 2014 by Frost & Sullivan. Fortis Escorts, a leading clinical research institute, typically has over 20 international cardiovascular trials underway at any one period of time. Dr. Suhail Bukari, Senior Consultant and Department Head of Vascular Surgery served as the primary investigator. Dr. Bukari previously served as a clinical investigator for the Juventas Therapeutics critical limb ischemia trial. Dr. Bukari noted “This is a significant breakthrough for medicine as all the patients enrolled were scheduled for amputation of their afflicted limb prior to consenting to the stem cell intervention.” He further noted, “the simple kit process will enable any surgeon treating peripheral vascular disease to have a readily available safe and autologous therapeutic to reverse this debilitating disease.”
Dr. Richard Powell, M.D., Chief for Vascular Surgery at Dartmouth-Hitchcock Medical Center, Professor of Surgery and Radiology at Dartmouth Medical School in New Hampshire and the chair/national principal investigator of Cesca’s upcoming pivotal CLIRST III study, commented that “No-option CLI patients will now have a potential treatment to salvage their limb and positively impact their quality of life”
Cesca’s CLIRST treatment harvests bone marrow from the patient’s hip bone and then uses proprietary devices to both separate therapeutic cells from the bone marrow and deliver them into the afflicted limb muscles. The devices are designed to minimize damage to the therapeutic cells which normally undergo high velocities and pressures as they pass through centrifugation devices, needles and catheters. The anticipated advantages of Cesca’s approach over the competition is that it (a) delivers a greater number of healthier therapeutic cells to the damaged tissue, and (b) does it at the point-of-care in less than 90 minutes - both shown to improve efficacy as preliminarily evidenced by the early Phase Ib CLI trial. The unique combination of multiple bone marrow derived cells and factors has multiple modes of action including engraftment and subsequent mobilization of the stem cell niche, and indirectly through the beneficial effects of the implanted factors and new factors secreted by the implanted cells to create revascularization in local collaterals in the afflicted limb. This entire process can be done quickly in a single short visit to the operating room.
Cesca Files IDE Application With FDA For CLI Treatment
Cesca’s pivotal trial application milestone for the treatment of CLI is the culmination of nearly six years of focus on cardiovascular clinical trials and device engineering specifically designed to verify that a patient's own bone marrow stem cells can positively impact a debilitating and potentially fatal disease. The CLIRST III study, as proposed in the IDE application, is a double blinded randomized placebo controlled trial to evaluate the safety and efficacy of Cesca’s SURGWERKS-CLI and VXP System in CLI patients having non-healing foot ulcers who with no further surgical options, and will be compared against a placebo control of the same population. The primary endpoint is major amputation free survival at 12 months following enrollment. The study will be conducted in approximately 60 sites including up to 3 sites in India.
Competitive Cost Advantage and Reimbursement
Cesca’s CLIRST has a strong competitive cost advantage. Management estimates the CLIRST kit will cost less than $15,000 versus the significantly higher average CLI treatment cost today. The procedure is rapid, performed in the operating room in approximately 90 minutes and requires a patient hospital stay of only 24 hours.
Upon FDA pre-market approval (PMA) for the treatment, management expects the procedure will be reimbursable under Medicare Part A. Additionally, the company will be seeking reimbursement from Medicare for costs of the patient treatment during the trial and prior to the final marketing clearance by the FDA.
The Acute Myocardial Infarction Problem
AMI remains the leading cause of death and occurs when blood flow to the heart is interrupted leaving a portion of the heart damaged. The damaged part of the heart is unable to contribute to the demand for pumping action resulting in other parts of the heart overcompensating by working harder and consequently growing larger. This imbalance can lead to an enlarged heart (remodeling) and thereafter less effective pumping action in the left ventricle, leading to a significantly lower than normal (in the 35-40% range) Left Ventricle Ejection Fraction (LVEF). A normal LVEF is considered to be between 50% and 75%. Such a dramatic loss in pumping function leads to chronic heart failure.
Cesca has demonstrated in an early-stage clinical trial that Stem Cell Therapy has the potential to restore healthy blood flow to the heart and to regenerate the damaged tissue so that the heart can resume normal balance and pumping.
Promising AMI Trial Results
Cesca reported AMI Pilot study results in October 2013. In this open label single arm study, a single no-option ST Elevated Myocardial Infarction (STEMI) patient was enrolled with a very low and pharmaceutically unresponsive LVEF of 35% three days after emergency room admission and implantation of a coronary stent. The patient was treated using Cesca’s SurgWerks-AMI process on the 6th day after stent placement. Twenty-four months after treatment with Acute Myocardial Infarction Rapid Stem Cell Therapy ("AMIRST") the patient ended the study having experienced no Major Adverse Cardiovascular Events (Safety) and with an LVEF of 60.3%. There was also no further infarct scarring and undesirable remodeling. Low LVEF and heart remodeling are two key contributors in AMI patients advancing to heart failure.
Dr. Ashok Seth, Chairman - Cardiac Sciences team, Dr. Upendra Kaul, Dean of Academics – Cardiac Sciencies, and Dr. Vinay Sanghi, all of Fortis Escorts, conducted the clinical case study which shows the AMIRST treatment safely delivered to a single male patient an effective dose of autologous selected stem cells in a single intracoronary heart catheterization procedure. The Company believes this is the first cell therapy that integrates both devices and autologous biologicsin a single procedure that is administered at the point-of-care in 90 minutes.
Dr. Vinay Sanghi, Clinical Investigator and treating physician on this case, said "Conducting a fully-integrated point-of-care treatment on a patient with an acute ST-elevated myocardial infarction using the AMIRST protocol was straightforward and very exciting as a practicing interventional cardiologist.” “The safety and positive clinical benefits demonstrated in this single patient case study are very encouraging as we begin planning for a larger AMIRST Phase II (feasibility) study treating patients who have suffered this type of heart attack.
The Company believes that this pilot case study affirmed that our cell therapy treating STEMI patients has appropriately considered the essential devices, diagnostics, cell formulation, and directions for use ensuring the AMIRST treatment meets the objectives of providing a safe, effective, rapid, bedside therapy for treating low ejection fraction after a primary myocardial infarction. Cesca is enthusiastically looking forward to conducting a randomized placebo controlled Phase Ib study in India in 2015.
CLIRST and AMIRST Commercialization
If the Phase III pivotal CLI trial results are comparable to prior trial results, Cesca anticipates filing a PMA Application for marketing clearance in 2017 and could be delivering SurgWerks-CLI kits and VXP Systems for CLI patients before the end of 2017. An AMI Phase II Trial, discussed above, is also being planned for 2015 making for a very exciting year. The use of a patient’s own bone marrow cells within the operating room contribute to the safety and cost-effectiveness of Cesca’s model.
These types of clinical results give the Company confidence that our system and protocol for delivering personalized stem cell-based medicine can make a meaningful impact on the lives of our patients, and that seeking Pre-Market Approval from the FDA upon completion of our pivotal Phase three trials will be the most effective way of achieving broad adoption of our cell therapies in the marketplace.
Cell Therapy, also known as Regenerative Medicine, has been heralded as the future of medicine for decades. Treatments and cures have taken far longer than thought, but now armed with exciting clinical trial results, Cesca Therapeutics is positioning to being able to deliver desperately needed personalized and cost-effective treatments for CLI and AMI as well as a host of other common illnesses
For more information about Cesca Therapeutics, Inc., go to: www.CescaTherapeutics.com
The company paid consideration to SNN or its affiliates for this article.
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