Chronic Kidney Disease
An estimated 13% of Americans have chronic kidney disease (CKD). Regardless of disease origin, fibrosis is a final common pathway in CKD that leads to disease progression and ultimately organ failure. FibroGen is developing anti-CTGF therapy to slow kidney decline by direct intervention in the fibrotic pathway, and recent research suggests additional benefits of blocking CTGF may be achieved in earlier stages of CKD, such as reduction of proteinuria.
Chronic kidney disease (CKD) is progressive, not curable, and ultimately fatal, either because of the consequences of kidney failure or due to an alarmingly high level of cardiovascular mortality in the CKD patient population.
The first formal classification system for defining stages of CKD progression was presented to the medical community in 2002 when a working group of the National Kidney Foundation (NKF) issued clinical practice guidelines based on using serum creatinine as a biochemical parameter to estimate glomerular filtration rate (GFR). GFR is an indicator of overall kidney function and declines slowly with age or potentially more rapidly as a result of disease or injury. In 2005, CKD including end-stage renal disease (ESRD), accounted for 27% of Medicare expenses ($60 billion) and 36% of care for patients dually covered by Medicare and Medicaid ($18 billion). With approximately 29 million Americans affected today, CKD is a crisis in the US healthcare system.
Blocking CTGF Activity to Treat CKD
Regardless of disease etiology, tubulointerstitial fibrosis is a final common pathway in CKD that leads to disease progression and ultimately ESRD. CTGF has been implicated in this process through its effects on promoting epithelial to mesenchymal transition (EMT), a process whereby injured tubular epithelial cells morph into mesenchymal cells that mainly produce components of scar tissue. Recent studies also implicate CTGF in multiple other pathologies associated with CKD including hyperfiltration, proteinuria, hypertrophy, and microvascular leakage. There is emerging evidence that anti-CTGF therapy may provide some degree of reversal of the disease process.
FibroGen believes that directly blocking CTGF will represent a first-in-class therapy that may provide a critical renoprotective benefit resulting in decreased proteinuria and slower decline of renal function. The results of administration of FG-3019, FibroGen’s fully human monoclonal antibody against CTGF, in multiple experimental models of renal disease support its therapeutic potential in CKD. In models of renal fibrosis and DKD (using “db/db” diabetic mice and a combination of STZ-induced type 1 diabetes and renal ischemia-reperfusion injury), results demonstrated that FG-3019 significantly reduced urinary albumin or total protein excretion, improved kidney function (as measured by GFR), ameliorated renal hypertrophy and decreased fibrosis. Preliminary findings in clinical studies of FG-3019 in the settings of microalbuminura are also encouraging.
Diabetic Kidney Disease (DKD)
While there are many causes of CKD, DKD refers specifically to kidney disease related to diabetes. FibroGen has completed a phase 1 study of FG-3019 in patients with diabetes and microalbuminuria in which FG-3019 appeared to have a rapid effect on reducing proteinuria. The treatment phase has been completed in a similar phase 1 study of FG-3019 in patients with macroalbuminuria, and a phase 2 study of FG-3019 is underway in patients with type 2 diabetes and advanced kidney disease. Read more
FibroGen’s research efforts in DKD are focused on addressing cardiovascular comorbidity, which accounts for over three quarters of deaths of people with DKD. Research has demonstrated that FG-3019 can partially reverse arterial stiffening in diabetic animals, suggesting the possibility of reversing fibrosis in DKD. Read more
