Document Type

Article

Publication Date

6-2024

Identifier

DOI: 10.1016/j.xkme.2024.100833; PMCID: PMC11145552

Abstract

RATIONALE & OBJECTIVE: Sparsentan is a novel, non-immunosuppressive, single-molecule, dual endothelin angiotensin receptor antagonist (DEARA) examined in the ongoing phase 2 DUET trial for focal segmental glomerulosclerosis (FSGS). In the DUET 8-week double-blind period, sparsentan resulted in greater proteinuria reduction versus irbesartan. We report the long-term efficacy and safety of sparsentan during the open-label extension over more than 4 years.

STUDY DESIGN: Patients were examined from their first sparsentan dose (double-blind period or open-label extension) through 4.6 years.

SETTING & PARTICIPANTS: Patients with FSGS, excluding secondary FSGS.

INTERVENTION: Sparsentan (200, 400, and 800 mg/d).

OUTCOMES: Urinary protein-creatinine ratio, FSGS partial remission endpoint (urinary protein-creatinine ratio ≤1.5 g/g and >40% reduction from baseline), estimated glomerular filtration rate, and blood pressure approximately every 12 weeks. Treatment-emergent adverse events by year and cases/100 patient-years.

RESULTS: 109 patients were enrolled; 108 received ≥1 sparsentan dose; 103 entered the open-label extension (68 sparsentan, 35 irbesartan during the double-blind period). Sparsentan was ongoing in 45/108 patients (41.7%); median time to treatment discontinuation was 3.9 years (95% CI, 2.6-5.2). Mean percent proteinuria reduction from baseline was sustained through follow-up. Achieving partial remission within 9 months of first sparsentan dose (52.8% of patients) versus not achieving (47.2%) was associated with significantly slower rate of estimated glomerular filtration rate decline over the entire treatment period (-2.70 vs -6.56;

LIMITATIONS: The open-label extension does not include a comparison group.

CONCLUSIONS: Long-term sparsentan treatment showed sustained proteinuria reduction and a consistent safety profile.

Journal Title

Kidney Med

Volume

6

Issue

6

First Page

100833

Last Page

100833

Keywords

FPRE; FSGS partial remission endpoint; eGFR slope; kidney function; open-label extension; proteinuria; randomized controlled clinical trial; sparsentan

Comments

This is an open access article distributed under the terms of the Creative Commons CC-BY license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Publisher's Link: https://www.kidneymedicinejournal.org/article/S2590-0595(24)00044-X/fulltext

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