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
- Derebail, Vimal K., UNC School of Medicine, Chapel Hill , North Carolina, United States
- Murphy, Edward, Retrophin, Inc., Portland, Oregon, United States
- Raguram, Partha C., Catholic Health Initiatives Franciscan, Tacoma, Washington, United States
- Pergola, Pablo E., Renal Associates, PA, San Antonio, Texas, United States
- Sanghani, Neil S., Vanderbilt University , Nashville, Tennessee, United States
- Trachtman, Howard, NYU School of Medicine , New York, New York, United States
- Komers, Radko, Retrophin, Inc., Portland, Oregon, United States
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 – Retrophin, Inc., San Diego, CA