ASN's Mission

ASN leads the fight to prevent, treat, and cure kidney diseases throughout the world by educating health professionals and scientists, advancing research and innovation, communicating new knowledge, and advocating for the highest quality care for patients.

learn more

Contact ASN

1401 H St, NW, Ste 900, Washington, DC 20005

email@asn-online.org

202-640-4660

The Latest on Twitter

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

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