Kidney Week

Abstract: FR-OR087

Long-Term Effects of Sparsentan, a Dual Angiotensin and Endothelin Receptor Antagonist in Primary Focal Segmental Glomerulosclerosis (FSGS): Interim 84-Week Analysis of the DUET Trial

Session Information

• Glomerular Diseases: Clinical, Outcomes, and Trials
  October 26, 2018 | Location: 24A, San Diego Convention Center
  Abstract Time: 06:18 PM - 06:30 PM

Category: Glomerular Diseases

• 1203 Glomerular Diseases: Clinical, Outcomes, and Trials

Authors

• Hogan, Jonathan J., University of Pennsylvania , Philadelphia, Pennsylvania, United States

Jonathan J. Hogan, MD

• Derebail, Vimal K., UNC School of Medicine, Chapel Hill , North Carolina, United States

Vimal K. Derebail,

• Murphy, Edward, Retrophin, Inc., Portland, Oregon, United States

Edward Murphy,

• Raguram, Partha C., Catholic Health Initiatives Franciscan, Tacoma, Washington, United States

Partha C. Raguram,

• Pergola, Pablo E., Renal Associates, PA, San Antonio, Texas, United States

Pablo E. Pergola,

• Sanghani, Neil S., Vanderbilt University , Nashville, Tennessee, United States

Neil S. Sanghani,

• Trachtman, Howard, NYU School of Medicine , New York, New York, United States

Howard Trachtman,

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

Radko Komers,

Background

DUET is a phase 2, randomized, active-control study of patients (pts) 8–75 years with primary FSGS, estimated glomerular filtration rate (eGFR) >30 mL/min/1.73 m², and urine protein-to-creatinine ratio (UP/C) ≥1 g/g. Pts (N=109) were randomized to sparsentan (SPAR; 200, 400, or 800 mg/d) or irbesartan (IRB; 300 mg/d) for 8-week double-blind (DB) treatment in addition to current standard of care (including immunosuppressive treatments), followed by SPAR only (SPAR:SPAR, IRB:SPAR) in the open-label extension (OLE). This interim analysis was performed at Week 84.

Methods

In the OLE, UP/C, blood pressure (BP), eGFR, and FSGS partial remission endpoint (FPRE; UP/C ≤1.5 g/g and >40% UP/C reduction) were assessed every 12 weeks and compared with baseline (Week 0 for SPAR:SPAR; Week 8 for IRB:SPAR).

Results

UP/C, BP, and eGFR data are in the Table. SPAR:SPAR and transition to SPAR, at Week 8 in IRB:SPAR, led to statistically significant reductions in UP/C and BP, sustained to Week 84. FPRE was achieved by 27/45 (60%) SPAR:SPAR and 13/26 (50%) IRB:SPAR pts at Week 84. In both groups, eGFR decreased initially and stabilized with increasing follow-up duration, possibly reflecting early hemodynamic effects of the drug. During SPAR treatment, adverse events were reported in 63 (94%) SPAR:SPAR and 32 (91%) IRB:SPAR pts; headache, peripheral edema, and hypotension occurred in >20% of pts in SPAR:SPAR or IRB:SPAR.

Conclusion

Sparsentan achieved sustained protein-lowering and BP-lowering effects in primary FSGS over 84 weeks, suggesting long-term nephroprotective potential of the drug.

Funding

• Commercial Support –