Chronic and hard-to-heal wounds are a serious and growing $5.3-billion problem affecting more than 2 million people in the United States, European Union and Japan. Common results of chronic wounds include comorbidities and mortality, lengthened hospital stays and a significant increase in the cost of care, all of which have a negative impact on the quality of life of both the patients and caregivers. DDNews recently explored possible remedies with Nissim Mashiach, president and CEO of the Israeli company Macrocure Ltd.
DDNews: Nissim, could you explain to our readers your company’s track record in regenerative medicine, wound care and the development and commercialization of biologics?
Nissim Mashiach: Founded in 2008, Macrocure is focused on developing a novel therapeutic platform to address chronic and hard-to-heal wounds, such as diabetic foot ulcers (DFUs) and venous leg ulcers (VLUs). My company’s lead product candidate, CureXcell, is a monthly injectable of living, human, activated white blood cells. More than 5,000 patients have been treated in Israel to date, where it has been approved for commercialization for the past 17 years. We are currently in two pivotal double-blind Phase 3 clinical trials in the U.S., with data expected in the second half of 2015. My management team has a wide range of experience in developing and commercializing biologics. For example, I have worked at Ethicon (Johnson & Johnson) and Omrix Biopharmaceuticals.
DDNews: How does your product’s contact with the injured person’s wound bed trigger a body’s endogenous healing process?
Mashiach: The healing process can be triggered by the injection of a mixture of activated white blood cells obtained from young healthy donor blood into the wound bed. The mixture can replenish the imbalanced inflammatory environment in the nonhealing wound with functionally active immune cells that release the necessary growth factors and are capable of phagocytosis of bacteria and dead cells in the wound bed. Recent findings from our mechanism of action study confirmed that CureXcell has over 55 growth factors and cytokines that participate in all stages of wound healing. The amplification of the cytokines and growth factors found in CureXcell assures a very high concentration of these activated growth factors, which can explain the high closure rate our product has demonstrated versus standard of care in our previous clinical studies. By recreating the natural environment for wound healing, the appropriate cell activities and factor secretions are maintained as required during wound healing.
DDNews: Will CureXcell have applications beyond chronic and hard-to-heal wounds such as DFUs and VLUs?
Mashiach: Yes, CureXcell has potential market applications in a wider range of regenerative medicine applications, including aesthetic surgery, orthopedic surgery and reconstructive surgery. One of the reasons why we are doing robust clinical studies is that we see CureXcell as a platform technology that may be applicable in many indications beyond wound healing.
DDNews: Would you explain to our readers the important commercial potential of your company and its products?
Mashiach: Chronic, hard-to-heal wounds represent one of the largest, fastest-growing segments of the wound-care market. The worldwide advanced wound-care market has existing sales of approximately $5.3 billion; there are approximately 800,000 new DFU patients and approximately 1,300,000 new VLU patients each year in the U.S., EU and Japan. Twenty-five percent of diabetes patients will develop a foot ulcer; currently, 15 percent of hard-to-heal wounds result in amputations. In fact, 80 percent of all amputations in the U.S. are the result of non-healing DFUs. Overall, the problem places a $25-billion burden on the U.S. healthcare system, which we believe we can help alleviate. In addition to this high unmet medical need, there is an existing desire on the part of physicians for alternate treatment options that are backed by strong clinical data and favorable reimbursement. We believe that CureXcell can address these unmet medical needs and become an attractive solution for physicians and patients.
DDNews: Please explain the Macrocure process, i.e., how it functions to heal wounds.
Mashiach: CureXcell is an injectable suspension of living white blood cells, including macrophages, neutrophils and lymphocytes, which are crucial to initiating, promoting and completing the process of cellular regeneration and wound healing. Macrocure activates the white blood cells via its proprietary hypo-osmotic shock cell activation technology, a process that changes the concentration and pH of the suspension surrounding the cells. Once activated, these cells undergo a change in gene expression that results in an increase in the cells’ secretion of numerous growth factors and other biochemical factors.
A physician draws CureXcell from its sterile package using a standard syringe for injection into a patient’s wound. A direct application into the wound bed is a major advantage, in that it allows the treatment to bypass the biofilm and contaminated environment and promote healing from the inside out. And as a major boon to patients, the therapy involves only one injection per month.
DDNews: What are the regulatory hurdles you may still face in the U.S. to obtain FDA approval for this unique product?
Mashiach: FDA approval is contingent upon meeting the DFU and VLU clinical trial endpoints (we expect to report full and interim data in the second half of 2015, file our BLA in the second half of 2016 and obtain approval in late 2017). We are seeking a broad-label indication for CureXcell for all wounds below the knee.
DDNews: What have been the results of clinical studies thus far?
Mashiach: An Israeli clinical trial harnessing CureXcell has shown that after only approximately three injections directly into the wound bed, there was a 64-percent closure rate in DFU and over 80 percent in VLU. The current clinical trials in the U.S. are designed similarly to the Israeli trial in terms of inclusion/exclusion criteria. The trial is enrolling the worst of the worst and includes patients with low ABI and infection, and can include patients post-amputation.
Nissim Mashiach has served as president and CEO of Macrocure Ltd. since June 2012. Before joining Macrocure, he served as general manager at Ethicon, a Johnson & Johnson company, from 2009 to 2012. Prior to that, he served as president and CEO at Omrix Biopharmaceuticals Inc., a company acquired by Johnson & Johnson in 2008. Prior to Omrix, Mashiach held various leadership positions at several pharmaceutical companies. He holds an MBA from the University of Manchester in England, a master of pharmaceutical science degree from the Hebrew University in Jerusalem and a bachelor’s degree in chemical engineering from the Technion-Israel Institute of Technology in Haifa, Israel.