Sustained release gel enabling one-stage treatment of prosthetic joint infection

Prosthetic joint infections (PJIs) are a serious complication of total joint replacement surgery. PJIs accounted for about $6 billion in healthcare costs in 2018. Unfortunately, treatment of PJI is under-reimbursed, and healthcare reforms are putting increasing economic pressure on hospitals to bear the high costs of treating these infections. New technologies are badly needed to improve the quality of care and costs associated with treating PJI.PJIs are caused by bacteria in biofilms which require extreme sustained concentrations of antimicrobials to eradicate. PJIs are treated with two surgeries. In the first, the infected implant and tissues are removed (debridement) followed by local delivery of high concentrations of antimicrobials to eradicate any residual biofilm contamination. Currently, local delivery is achieved using bone cement andquot;spacersandquot; which require removal in a second surgery. A product that provides local delivery and is also compatible with insertion of a permanent implant would enable effective PJI treatment in a single surgery, improving patient outcomes and reducing costs.We have developed a new degradable sustained-release carrier, SB Gel, which is capable of delivering high and sustained antimicrobial concentrations throughout a surgical site, including over the entire surface of a joint prosthesis. SB Gel is the only material to provide high, sustained antibiotic release sufficient to eliminate contamination in the surgical site (including biofilm), compatibility on all implant and tissue surfaces (including articulating surfaces), and safe dissolution over time to allow for normal healing without requiring later removal. SB Gel is loaded with the antimicrobials tobramycin and vancomycin in a formulation designated as SBG002. These drugs are effective against bacteria responsible for over 95% of PJIs. Preliminary studies demonstrate that SBG002 provides biofilm-eradicating antimicrobial levels in tissue, is compatible with bone-implant ingrowth and normal tissue healing, is safe at multiples of a human equivalent dose, and has unmatched effectiveness in successfully treating (20/20) an animal model of implant-associated biofilm infection in a single surgery treatment.We now propose continuing development in a Phase IIB project to complete all remaining work to bring SBG002 to readiness for a Phase 1 clinical trial including submission of an Investigational New Drug (IND) application to the FDA. In Aim 1, we will complete all remaining IND-enabling GLP toxicology and genotoxicity studies. In Aim 2, we will conduct all required manufacturing-related activities, including production and characterization of clinical trial material. Aim 2 will conclude with preparation and filing of an IND application for SBG002.Infections of hip and knee replacement surgeries cost the U.S. healthcare system about $6,000,000,000 in 2018. This project seeks to develop a new gel-based product which delivers antibiotics to the infected area, helping to kill the infection. This technology has the potential to significantly reduce the costs and risks associated with treating these infections.