NephroGenex, Inc. has completed phase II b trial of PYR-210 that studied the safety and efficacy of its lead drug candidate Pyridorin (pyridoxamine dihydrochloride) in type 2 diabetic patients with overt nephropathy.
PYR-210 evaluated two doses of Pyridorin against placebo in 317 patients over a one year treatment period. Patients enrolled in the trial were type 2 diabetic patients with elevated serum creatinine (SCr) levels and significant proteinuria, and were on standard of care which included adequate blood pressure control and a stable regimen of ACEi/ARB therapy. Efficacy was evaluated based on a 12 month change in SCr from baseline.
As reported in the current online issue of the Journal of the American Society of Nephrology, Pyridorin was well tolerated and has a benign safety profile. Pyridorin did not produce a significant treatment effect in the entire patient population treated; however, in patients with less severe disease (i.e. baseline SCr values less than 1.9 mg/dL), Pyridorin did produce a treatment effect greater than 50% relative to placebo that is statistically significant.
Patients treated with Pyridorin who were on previously established standard of care at screening, with a baseline SCr of up to 3 mg/dL, which includes patients with both mild and moderate levels of disease, showed a highly significant 57% treatment effect for the 300 mg arm (P = 0.009; n=64) and 45% for the 150 mg arm (P=0.045; n=62) relative to placebo. Pyridorin also slowed the progression of cystatin C and caused a reduction in urinary TGFß in this patient population.
Approximately 70 to 80 per cent of diabetic overt nephropathy patients have SCr values less than 2 mg/dL and approximately 80 to 90 per cent have SCr values less than 3 mg/dL. Thus, Pyridorin therapy has demonstrated efficacy in the large majority of diabetic patients with overt nephropathy. In two previous phase IIa trials, Pyridorin therapy demonstrated a significant treatment effect in slowing the progression of diabetic nephropathy as measured by the change in serum creatinine over a six month treatment period. Pyridorin therapy also demonstrated a reduction in urinary TGFß, an important marker of glomerulosclerosis and tubulointerstitial fibrogenesis.
Diabetic kidney disease afflicts approximately one-third of all diabetics and is the major cause of ESRD, which is a significant component of healthcare expenditures. Mortality rates for ESRD patients can reach 20 per cent annually. Pyridorin has been awarded Fast Track status by the FDA due to the unmet medical need of patients with this life threatening disease.