Chinook plans to initiate a Phase 3 clinical trial of atrasentan in the second half of 2020 for biomarker-selected patients with a rare primary glomerular kidney disease at high risk for progressive kidney function loss. In a randomized placebo-controlled trial of 3,600 patients with diabetic kidney disease, atrasentan significantly reduced proteinuria, delayed progression to end-stage renal disease (ESRD) and demonstrated an acceptable safety profile suitable for long-term dosing. These data indicate atrasentan has potential to preserve and protect kidney function in patients with severe kidney diseases, including primary glomerular diseases where reductions in proteinuria have emerged as a surrogate endpoint for accelerated regulatory approval.
Atrasentan is a potent and highly selective blocker of the ETA receptor
Atrasentan is a potent and highly selective blocker of the endothelin A (ETA) receptor, which is activated in human primary glomerular diseases and can cause proteinuria, kidney inflammation and scarring that contributes to progressive kidney function loss. Elevated kidney ET-1 expression prospectively predicts rapid progression in primary glomerular diseases. There are currently limited treatment options for primary glomerular diseases, which are estimated to affect over 250,000 patients in the US. Medical management is largely non-specific, aimed at reducing blood pressure, along with the potential use of immunosuppressive agents that typically provide insufficient therapeutic benefit and are often accompanied by negative side effects.