Programs
Atrasentan
Atrasentan is a potent and selective endothelin A receptor antagonist with the potential to provide benefit in IgA nephropathy and other proteinuric glomerular diseases by reducing proteinuria.
Atrasentan in Action
Watch our video to learn more about atrasentan’s proteinuria-lowering mechanism of action as well as its anti-fibrotic and anti-inflammatory properties in proteinuric glomerular diseases.
The phase 3 ALIGN trial of atrasentan is currently enrolling patients with IgA nephropathy and the phase 2 AFFINITY trial of atrasentan is currently enrolling patients with proteinuric glomerular diseases. We identified IgAN as the lead indication for evaluation of atrasentan due to the role of endothelin activation and proteinuria in IgAN disease progression and high unmet need with the potential to submit an NDA seeking accelerated approval based on surrogate endpoints.
We in-licensed atrasentan from AbbVie in 2019. AbbVie previously developed atrasentan for diabetic kidney disease through multiple clinical trials, including >5,000 patients in their phase 3 SONAR trial. In SONAR, atrasentan showed a statistically significant p-value of 0.029 on its primary endpoint of a composite of hard kidney outcomes (i.e., first occurrence of progression to end-stage renal disease or doubling of serum creatinine). The study also demonstrated statistically significant reductions in proteinuria as well as improvements in eGFR, both of which are measures of kidney function.
IgA Nephropathy (IgAN)
Immunoglobulin A nephropathy (IgAN) is the leading cause of primary glomerulonephritis worldwide, with an estimated incidence of 1.29 per 100,000 individuals per year in the United States. The global incidence of IgAN is approximately 2.5 per 100,000 individuals per year. Higher reported incidence in Asia and Europe compared to the United States is, in part, due to regional differences in urine screening, referral patterns and indications for biopsy. IgAN is associated with progressive loss of kidney function leading to end-stage kidney disease (ESKD) in 24 to 53% of IgAN patients over 10 to 30 years, representing a significant unmet need for new treatment options.
Galactose-deficient immunoglobulin A1, or Gd-IgA1, is recognized as a critical autoantigen to which IgAN patients develop circulating autoantibodies, resulting in the formation and deposition of immune complexes in the glomeruli of the kidney. This process initiates an inflammatory cascade that damages the glomeruli, resulting in protein and blood leaking into the urine, called proteinuria or hematuria, respectively.
Ultimately the filtration function of the kidney is impaired, reducing the ability to remove waste products from the blood. As the disease progresses, these waste products accumulate and can result in potentially life-threatening complications that often lead to the need for dialysis or kidney transplant. Sustained proteinuria is the most widely studied and the strongest predictor for the rate of progression to ESKD in IgAN.
Nature Reviews, February 2016
endothelin A receptor
Atrasentan is a selective and potent inhibitor of the endothelin A (ETA) receptor, which has the potential to provide benefit in multiple chronic kidney diseases by reducing proteinuria and having direct anti-inflammatory and anti-fibrotic effects to preserve kidney function.
Kidney Intl., November 2014
Clinical trials
The ALIGN study, a phase 3, randomized, double-blind, placebo-controlled trial of atrasentan in patients with IgAN at risk of progressive loss of kidney function, is designed to evaluate change from baseline in proteinuria and eGFR in 320 patients with IgAN. Sustained proteinuria is the most widely studied and the strongest predictor for the rate of progression to ESKD in IgAN, and may be accepted as a surrogate endpoint for regulatory approval. Sustained proteinuria is the most widely studied and the strongest predictor for the rate of progression to ESRD in IgAN, and may be accepted as a surrogate endpoint for regulatory approval. This global study is being conducted in approximately 20 countries across four continents at approximately 160 - 170 investigative sites. For more information, visit www.alignstudy.com or contact clinicaltrials@chinooktx.com.
The AFFINITY study, Chinook’s phase 2 open-label basket trial of atrasentan in additional proteinuric glomerular diseases, is currently enrolling patients. Four initial cohorts will consist of patients with: IgAN with urine protein to creatinine ratio (UPCR) of 0.5 to less than 1.0 g/g, focal segmental glomerulosclerosis (FSGS), Alport syndrome and diabetic kidney disease (DKD) in combination with an SGLT2 inhibitor. For more information, visit the AFFINITY study website or contact clinicaltrials@chinooktx.com.