Kidney Week

Abstract: FR-OR026

Long-Term Effect of Sparsentan (SPAR), a Dual Angiotensin and Endothelin Receptor Antagonist, on Proteinuria in Patients with Primary FSGS: Interim Analysis of the DUET Trial

Session Information

• Clinical Glomerular Disorders: Clinical Translational Science
  November 03, 2017 | Location: Room 292, Morial Convention Center
  Abstract Time: 05:30 PM - 05:42 PM

Category: Glomerular

• 1005 Clinical Glomerular Disorders

Authors

• Trachtman, Howard, NYU Langone Med Ctr, New York City, New York, United States

Howard Trachtman, MD, FASN

• Rychlik, Ivan, Charles University, 3rd Faculty of Medicine, Prague 10, Czechia

Ivan Rychlik,

• Haws, Robert M., Marshfield Clinic, Marshfield, Wisconsin, United States

Robert M. Haws,

• Nester, Carla M., University of Iowa, Iowa City, Iowa, United States

Carla M. Nester,

• Fornoni, Alessia, University of Miami, Miami, Florida, United States

Alessia Fornoni,

• Komers, Radko, Retrophin, Inc., Portland, Oregon, United States

Radko Komers,

Background

In the ongoing DUET trial, SPAR (200, 400, 800 mg/day) resulted in greater reduction in proteinuria vs. irbesartan (IRB, 300 mg/day) over the 8-week double-blind (DB) period. Generally, SPAR was safe and well tolerated. After DB, patients were treated in an open-label extension (OLE). We present interim results of OLE for sustainability of the antiproteinuric effect of SPAR.

Methods

In the OLE, patients [biopsy-proven FSGS, baseline (BL) urine protein/creatinine ratios (Up/C)>1g/g, age 8-75 y (U.S.), eGFR>30 ml/min] randomized to SPAR continued (SPAR:SPAR), and those randomized to IRB received SPAR (IRB:SPAR). Up/C, eGFR and blood pressure (BP) were measured every 12 weeks to Week 48 and compared to BL (Week 0 for SPAR:SPAR; Week 8 for IRB:SPAR).

Results

Results of patients with available Up/C are below. In SPAR:SPAR, SPAR resulted in rapid reduction of Up/C and BP which remained sustained over 48 weeks, while eGFR remained stable. In IRB:SPAR group, transition to SPAR resulted in a significant reduction in Up/C (Week 16), which was sustained until the end of follow-up. In contrast to SPAR:SPAR, IRB:SPAR was associated with mild, temporary, but significant reduction in eGFR, while SPAR-induced BP reduction was less apparent.

Conclusion

SPAR was well tolerated and achieved a sustained antiproteinuric effect in primary FSGS with early BP reduction and stable eGFR over 48 weeks. Transition to SPAR from IRB led to significant, sustained reduction of proteinuria and a temporary, mild reduction in eGFR without long-term impact on BP.

Funding

• Commercial Support – Retrophin, Inc.