Abstract: SU-OR38
Complete Remission of Proteinuria in Patients with Focal Segmental Glomerulosclerosis Treated with Sparsentan, a Dual Endothelin and Angiotensin Receptor Antagonist, in the DUET Trial
Session Information
- Halfway Through the Marathon: Clinical Candidates in Development
October 25, 2020 | Location: Simulive
Abstract Time: 05:00 PM - 07:00 PM
Category: Glomerular Diseases
- 1203 Glomerular Diseases: Clinical, Outcomes, and Trials
Authors
- Hogan, Jonathan, Perelman School of Medicine, University of Pennsylvania,, Philadelphia, Pennsylvania, United States
- Diva, Ulysses, Retrophin, Inc., San Diego, California, United States
- Murphy, Edward, Retrophin, Inc., San Diego, California, United States
- Rosenberg, Noah, Retrophin, Inc., San Diego, California, United States
- Trachtman, Howard, NYU School of Medicine, NYU Langone Medical Center, New York, New York, United States
- Komers, Radko, Retrophin, Inc., San Diego, California, United States
Background
In FSGS, partial remission (FSGS partial remission endpoint [FPRE]: 40% proteinuria reduction and urine protein/creatinine ratio (UP/C) <1.5 g/g) and complete remission (CR) of proteinuria are strong predictors of kidney survival. In the DUET trial, sparsentan (SPAR) resulted in greater reductions in proteinuria and higher rate of FPRE vs irbesartan (IRB) over the 8-week double-blind (DB) period. This antiproteinuric effect of SPAR was sustained during the open-label extension (OLE) period of DUET. Here we analyze patients who achieved CR (UP/C <0.3 g/g) in DUET.
Methods
DUET randomized patients age 8-75 years with biopsy-proven FSGS, UP/C>1 g/g, and eGFR>30 mL/min to SPAR or IRB for 8 weeks, followed by OLE with all patients receiving SPAR. UP/C and other parameters were measured every 12 weeks during OLE. This post-hoc analysis included all patients on SPAR treatment regardless of original randomization.
Results
Median follow-up on SPAR was 42.5 months. Of 108 subjects dosed with SPAR, 44 (41%) reached CR at least once and 30 (28%) patients reached CR in ≥2 visits (68% of CR patients). CR was achieved by 28 patients within the 1st year on SPAR (Kaplan-Meier estimate: 29%). A history of, or nephrotic syndrome at baseline, was documented in 8 (18%) of CR patients. Of subjects with CR, 14%, 41%, and 45% were originally assigned to 200, 400, and 800 mg/day of SPAR dose cohorts, respectively. No patient achieved CR while on IRB during the DB period. Compared to the overall DUET population, CR patients had similar age, sex, and baseline eGFR, but lower baseline mean UP/C (1.67 g/g vs 2.65 g/g), and higher proportion of baseline immunosuppression (45% vs 35%), in particular with mycophenolate mofetil (18% vs 12%). Achieving CR was associated with better preservation of kidney function compared to not achieving CR. In 6 patients (14%), occurrence of CR followed the initiation of new steroid treatment.
Conclusion
In the DUET trial, a high proportion of patients achieved CR on at least one occasion. These observations support the long-term nephroprotective potential of SPAR in FSGS.
Funding
- Commercial Support –