Sparsentan found effective in treating rare kidney disease

A new study published in the Journal of The American Society of Nephrology reports that Sparsentan was found safe and well tolerated in patients with Focal Segmental Glomerulosclerosis (FSGS) and achieved significantly greater reductions in proteinuria after 8 weeks of sparsentan compared to irbesartan.

With no approved treatments for FSGS, the field has sought to apply to it medications developed to treat other diseases, says Trachtman, including angiotensin II receptor blockers (ARBs) like irbesartan. Initially developed to treat high blood pressure, ARBs are currently used in lieu of an approved FSGS therapy. These drugs act by lowering the blood pressure within the filtering units of the kidney and reducing kidney scarring.

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The findings of phase II clinical trial showed that the drug is more than twice as effective as the standard treatment at reducing a key measure of severity in a rare kidney disease.

"This is the first large-scale clinical trial of a treatment designed specifically to target FSGS, a rare disorder estimated to affect up to 40,000 people in the United States, and for which there are currently no approved therapies," says principal investigator and lead study author Howard Trachtman. Nearly half of affected patients will progress to end-stage kidney disease, he says.

"Not only could sparsentan become part of the standard of care for patients with FSGS, but there are potential implications for any patient with kidney disease characterized by proteinuria -- including the more common IgA nephropathy which affects hundreds of thousands of people worldwide," says Dr. Trachtman.

Howard Trachtman and associates conducted a phase 2, randomized, double-blind, active-control trial to evaluate and compare the effects of sparsentan, a dual endothelin type A (ETA) and angiotensin II type 1 receptor antagonist, with those of the angiotensin II type 1 receptor antagonist irbesartan in patients with primary FSGS.

The 109 study participants aged 8–75 years with biopsy-proven FSGS, eGFR>30 ml/min per 1.73 m2, and urinary protein-to-creatinine ratio (UP/C) ≥1.0 g/g received sparsentan (200, 400, or 800 mg/d) or irbesartan (300 mg/d) for 8 weeks, were followed by open-label sparsentan only.

The key study findings included are as follows:

• Sparsentan-treated patients had greater reductions in UP/C than irbesartan-treated patients did when all doses (45% versus 19%) or the 400 and 800 mg doses (47% versus 19%) were pooled for analysis.


• The FSGS partial remission endpoint was achieved in 28% of sparsentan-treated and 9% of irbesartan-treated patients.


• After 8 weeks of treatment, BP was reduced with sparsentan but not irbesartan, and eGFR was stable with both treatments.


• Overall, the incidence of adverse events was similar between groups.


• Hypotension and edema were more common among sparsentan-treated patients but did not result in study withdrawals.

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"The prevalence of FSGS is on the rise, and this combined therapy could offer new hope for patients with this rare kidney disorder who currently face a progressive decline, a high chance of end-stage kidney disease, dialysis or transplantation," says Dr. Trachtman.

Focal segmental glomerulosclerosis (FSGS) encompasses a heterogeneous group of clinical conditions with defined glomerular histopathology. Patients with FSGS typically present with a variable degree of proteinuria and often nephrotic syndrome. Nephrologists use proteinuria as a measure, or marker, of the health of FSGS patients.

For full information log on to https://doi.org/10.1681/ASN.2018010091