More than 20 million Americans suffer from some level of CKD. Moreover, statistics shows that nearly 871,000 people are being treated for ESRD. The rate for ESRD has increased steadily in recent years, to ~1,738 cases per million Americans. Of these, nearly 398,000 ESRD patients were treated with some form of dialysis in 2009. 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.
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 have developed a humanized monoclonal antibody that neutralizes both the C3 and C5 convertases of the complement pathway by binding to the catalytic region of the complex. This antibody immediately disables the active convertase that is responsible for producing key inflammatory mediators required for chronic inflammation in hemodialysis. We have demonstrated that our humanized variants inhibit the formation of C3a/C5a/C5b-9 and corresponding cellular activation in whole blood extracorporeal hemodialysis model of inflammation. Our therapeutic humanized antibodies do not inhibit the pathway important for host defense.
NovelMed is currently seeking pharma/venture partners to develop its portfolio of unique therapies for orphan & non-orphan indications.