Abstract: FR-PO851
Concomitant Sparsentan (SPAR) and SGLT2 Inhibitors in Patients with IgA Nephropathy in the PROTECT Open-Label Extension (OLE)
Session Information
- IgA Nephropathy: Clinical, Outcomes, and Therapeutics
October 25, 2024 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1402 Glomerular Diseases: Clinical, Outcomes, and Therapeutics
Authors
- Kooienga, Laura, Colorado Kidney Care, Denver, Colorado, United States
- Malecki, Robert, Nephrology Department of MSS in Warsaw, Warsaw, Poland
- Preciado, Priscila, Travere Therapeutics, Inc., San Diego, California, United States
- Nandola, Heeral, Travere Therapeutics, Inc., San Diego, California, United States
- Mercer, Alex, JAMCO Pharma Consulting, Stockholm, Sweden
Group or Team Name
- On behalf of the DUPRO Steering Committee and PROTECT Investigators.
Background
SPAR, a nonimmunosuppressive, dual endothelin angiotensin receptor antagonist (DEARA), demonstrated superior efficacy for proteinuria reduction and better preservation of kidney function vs irbesartan in pts with IgAN in the PROTECT trial. SPAR combined with an SGLT2i may offer additive kidney protection. We report data from pts who were prescribed an SGLT2i added to ongoing SPAR treatment in the PROTECT OLE.
Methods
Pts who completed the PROTECT double-blind period and met eligibility criteria were enrolled in the PROTECT OLE. All pts received SPAR (target dose, 400 mg/d). Concomitant SGLT2i treatment could be initiated at any time during the OLE at investigator discretion. Pts were excluded from this analysis if they participated in the randomized controlled OLE SGLT2i substudy. Body weight, systolic and diastolic blood pressure, and urine protein-to-creatinine ratio (UPCR; based on 24-h urine sample) were evaluated at baseline (defined as the OLE visit closest to SGLT2i start) and at weeks 12, 24, 36, and 48 after baseline. Treatment-emergent adverse events (TEAEs) were examined.
Results
At data cutoff, 62 pts (mean [SD] age, 46 [11.3] y; female, n=16 [26%]) had received SPAR and add-on SGLT2i in the OLE. Median (IQR) time from OLE start to SGLT2i start was 273 (148.0-429.0) days. Summary data for body weight, blood pressure, and proteinuria over the 48 weeks are presented in the Table. Body weight and blood pressure remained relatively stable. Forty-one (66%) pts had TEAEs; the most common were COVID-19, hyperkalemia, hypertension, and hypotension.
Conclusion
These data show that an SGLT2i added to a stable dose of SPAR is generally well tolerated and may lead to further reductions in proteinuria. The safety and efficacy of sparsentan with or without concomitant SGLT2i treatment are also being investigated in a separate randomized substudy within the PROTECT OLE.
| Summary Data for Clinical Variables at Each Time Point During the PROTECT OLE for Pts Who Received SGLT2i Added to SPAR | |||||
| Pre-SGLT2i treatment baseline* | Week 12 (n=49) | Week 24 (n=42) | Week 36 (n=34) | Week 48 (n=26) | |
| Body weight, mean (SD), kg | 88.9 (29.37)† | 87.9 (29.93) | 84.1 (21.46) | 84.4 (22.61) | 88.2 (37.97) |
| Systolic blood pressure, mean (SD), mm Hg | 127.3 (12.04)‡ | 124.7 (13.10) | 123.6 (15.46) | 125.8 (13.03) | 120.5 (15.55) |
| Diastolic blood pressure, mean (SD), mm Hg | 81.6 (9.23)‡ | 80.6 (8.33) | 79.5 (9.15) | 80.7 (8.56) | 77.3 (9.98) |
| UPCR, median (IQR), g/g | 1.35 (0.82-2.48)§ | 1.16 (0.62-2.05)|| | 1.51 (0.55-2.45)¶ | 1.08 (0.66-2.80)# | 1.17 (0.61-2.82)** |
| OLE, open-label extension; pts, patients; SGLT2i, sodium-glucose cotransporter-2 inhibitor; SPAR, sparsentan; UPCR, urine protein-to-creatinine ratio. *Baseline was defined as the OLE visit closest to the start of SGLT2i medication. †n=59. ‡n=60. §n=62. ||n=44. ¶n=35. #n=31. **n=25. | |||||
Funding
- Commercial Support – Travere Therapeutics, Inc.