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Kidney Week

Abstract: SA-PO903

Concomitant Sparsentan and Sodium-Glucose Cotransporter-2 Inhibitors (SGLT2i) in Patients with IgA Nephropathy (IgAN) in the PROTECT Open-Label Extension (OLE)

Session Information

Category: Glomerular Diseases

  • 1402 Glomerular Diseases: Clinical, Outcomes, and Trials

Authors

  • Kooienga, Laura, Colorado Kidney Care, Denver, Colorado, United States
  • Malecki, Robert, Nephrology Department of MSS, Warsaw, Poland
  • Preciado, Priscila, Travere Therapeutics Inc, San Diego, California, United States
  • He, Ping, 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.
Background

Sparsentan (SPAR) is a non-immunosuppressive, single-molecule dual endothelin and angiotensin II receptor antagonist (DEARA). In the ongoing PROTECT trial SPAR is compared to irbesartan in patients with IgAN. SGLT2i may slow disease progression in IgAN as suggested in subgroup analyses from DAPA-CKD and EMPA-KIDNEY. Combined DEARA and SGLT2i therapy may provide additional kidney-protective effects with unknown adverse events. Concomitant treatment with SGLT2i was prohibited during the PROTECT double-blind period (DB); however, SGLT2i are allowed in the OLE. We report the early clinical experience of SGLT2i added to ongoing SPAR treatment in patients with IgAN enrolled in the PROTECT OLE.

Methods

Patients who completed the PROTECT DB and met eligibility criteria were enrolled in the PROTECT OLE. All patients received SPAR with a target dose of 400 mg/day. Investigators, at their discretion, could initiate concomitant SGLT2i treatment at any time during the OLE. Body weight, systolic and diastolic blood pressure, and urine protein/creatinine ratio (UP/C; based on 24-hour urine sample) were evaluated at baseline and at weeks 12, 24, and 36 after baseline. Baseline was defined as the OLE visit closest to SGLT2i start (ie, before or <14 days after). Treatment-emergent adverse events (TEAEs) were examined.

Results

At data cutoff, 21 patients (7 female) had received SPAR and add-on SGLT2i in the OLE. Mean (SD) age was 42 (11) years. Median (IQR) time from OLE start to SGLT2i start was 25 (11, 48) weeks. Summary data for selected variables are shown in Table. Eleven (52%) patients had TEAEs; most common were COVID-19, headache, hyperkalemia and hypotension in 2 patients (10%) each. Two patients discontinued SGLT2i and no patients discontinued SPAR.

Conclusion

Early clinical experience during the PROTECT OLE shows that SGLT2i added to a stable dose of SPAR appears to be generally well-tolerated. Data are consistent with an additive benefit on proteinuria. A randomized sub-study within the OLE is further investigating SPAR+SGLT2i combined treatment.

Funding

  • Commercial Support – Travere Therapeutics, Inc.