Pam Harrison

November 28, 2016


CHICAGO — Sparsentan, which was developed for the treatment of hypertension, is emerging as a targeted therapy for primary focal segmental glomerulosclerosis (FSGS), research from the phase 2 DUET trial suggests.

"Primary focal segmental glomerulosclerosis is a rare disease, characterized by proteinuria, that can lead to progressive scarring in the kidney," said investigator Howard Trachtman, MD, from the NYU Langone Medical Center in New York City.

Because there is currently no approved therapy for FSGS and because prevalence is increasing, "there is an urgent and really huge unmet need to treat these patients," he said during a news conference here at Kidney Week 2016.

"FSGS is the leading cause of nephrotic syndrome in end-stage kidney disease, necessitating dialysis or transplantation in all age groups," he added.

The reduction in proteinuria is significantly greater with sparsentan — which simultaneously blocks angiotensin II and endothelin 1 — than with irbesartan. "This could be a significant advance for the FSGS community," Dr Trachtman explained.

This could be a significant advance.

The DUET trial — one of the largest intervention trials ever conducted in this disease — involved 109 patients 8 to 71 years of age with biopsy-proven FSGS. The evaluable efficacy dataset consisted of 96 patients.

Patients were randomized to one of three doses of sparsentan — 200 mg, 400 mg, or 800 mg daily — or to the angiotensin II receptor antagonist irbesartan 300 mg daily.

The primary end point was change from baseline in the ratio of urine protein to creatinine. Secondary end points included a reduction of more than 40% in that ratio at week 8 and modified partial remission, defined as a ratio of at least 1.5 g/g.

Results at Week 8

As part of the prespecified analysis plan, all doses of sparsentan were pooled.

At week 8, mean reduction from baseline in the ratio of urine protein to creatinine was significantly greater in the sparsentan groups than in the irbesartan group. Mean reduction in the ratio was also significantly greater when just the 400 mg and 800 mg sparsentan groups were compared with the irbesartan group (47.4% vs 19.0%; = .011).

In addition, modified partial remission, which was strongly associated with the long-term preservation of renal function, was achieved by significantly more patients in the sparsentan groups than in the irbesartan group.

Complete remission, defined as a ratio of urine protein to creatinine above 0.3 g/g, was achieved by four patients in the sparsentan groups and no patients in the irbesartan group.

There were no specific differences in safety profiles between sparsentan and irbesartan. Overall, sparsentan appeared to be generally safe and well tolerated, Dr Trachtman reported.

Sparsentan has the potential to be the first treatment for this rare kidney disorder approved by the US Food and Drug Administration, he added.

All patients who completed the double-blind phase of DUET were invited to participate in an open-label extension of the trial, which the company plans to continue until the drug is approved.

The study was funded by Retrophin. Dr Trachtman reports serving as a consultant for Kaneka, Retrophin, Astellas, and Otsuka; a pending consultant for Bristol-Meyers Squibb; a scientific advisor for the Data Safety Monitoring Board (DSMB) RIVUR trial and the DSMB bumetanide-seizure trial; chair of the DSMB Otsuka trials of tolvaptan in children; a member of the steering committee for the abatacept trial; and a member of the Medicare Evidence Development and Coverage Advisory Committee for BMS.

Kidney Week 2016: American Society of Nephrology Annual Meeting: Abstract HI-OR06. Presented November 19, 2016.


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