More than 20 million americans suffer from some level of chronic kidney disorder (CKD) as a primary or a secondary indication. Moreover, statistics shows that nearly 871,000 people are being treated for end stage kidney disease (ESRD). The rate for ESRD has increased steadily in recent years to few cases per million americans. Of these nearly large number of patients undergo some form of dialysis. Dialysis is mandatory for both these stages to improve and support any remaining kidney function.
It is well documented that blood contact with the artificial surfaces of a dialyzer activates the alternative complement pathway. Since these initial findings, the role of the complement system has been clearly established by several groups and studies. Complement activation can ultimately result in lysis of erythrocytes, causing anemia and kidney failure. Complement activation leads to cellular activation and cell death leading to increased lactate dehydrogenase (LDH) levels, and thrombosis. The breakdown of cells and subsequent release of LDH can cause liver and kidney failure, and can induce anemia. Our lead drug candidate is expected to benefit such patients via its unique mechanism of action.
Hemodialysis causes a complex inflammatory response, which results in acute and chronic inflammatory complications. Among these complications are respiratory failure, bleeding disorders (platelet dysfunction), further renal dysfunction, cardiovascular disease, cognitive deficits, multiple organ failure, and in severe cases, even death. Despite an unmet need, no complement inhibitors have yet been developed or approved for hemodialysis and therefore discussion of other products has been limited in this application.
Current efforts to address this unmet need focus almost exclusively on developing improved biomaterial to reduce contact activation. FDA approved heparin-coated biomaterial or advanced polysulfone-based materials reduce inflammation on a short-term basis but are not capable of preventing issues arising from repeated dialysis. Occasionally patients have been treated with corticosteroids & antioxidants with little or no success. Unfortunately, no complement inhibitors have been developed for the treatment of hemodialysis-induced complications in CKD and ESRD patients. Thus, chronic inflammation is on a rise in patients undergoing repeated hemodialysis procedures.
We believe that NM8074 could reduced complications that arise from hemodialysis that leads to renal inflammation during repeated dialysis.