Implementing the Kidney Health Initiative Surrogate Efficacy Endpoint in Patients With IgA Nephropathy (the PROTECT Trial)
Kidney International Reports – 2019
Efficacy and Safety of Sparsentan Versus Irbesartan in Patients With IgA Nephropathy (PROTECT): 2-year Results From a Randomised, Active-Controlled, Phase 3 Trial
Journal article
Published on November 3, 2023
Contributors:
Rovin BH, Barratt J, Heerspink HJL et al.
Rovin BH, Barratt J, Heerspink HJL et al.
DOI:
10.1016/S0140-6736(23)02302-4
10.1016/S0140-6736(23)02302-4
Summary
Background
- IgA nephropathy is a rare kidney disease. It can lead to progressive kidney function decline and kidney failure within 10 to 20 years of diagnosis1,2
- Endothelin-1 (ET-1) and angiotensin II (Ang II) are two critical peptides that act in tandem and are responsible for the progression of IgA nephropathy over time3,4
- Sparsentan is an FDA approved non-immunosuppressive, single-molecule, Dual Endothelin Angiotensin Receptor Antagonist (DEARA) indicated to slow kidney function decline in adults with primary IgA nephropathy who are at risk for disease progression5,6
Learn more about the two-year findings from PROTECT
Aim
The PROTECT study evaluates long-term efficacy and safety of sparsentan versus irbesartan in IgA nephropathy6
PROTECT: A large, international, randomized,<br /> double-blind, active controlled Phase 3 trial
Key findings
Sparsentan met its primary endpoint showing superior reductions in proteinuria from baseline to Week 36 versus irbesartan. This reduction was sustained over 2 years5-7
The absolute LS mean change in eGFR from baseline to Week 110 was smaller with sparsentan versus irbesartan, demonstrating a greater preservation of kidney function with sparsentan5,6
The safety profile of sparsentan is comparable with that of irbesartan5,6
The most common AEs with sparsentan were hyperkalemia,† hypotension, peripheral edema,† dizziness,† anemia, acute kidney injury, and transaminase elevations5‡
Most common AEs are per the FDA US Prescribing Information
There were no instances of drug-induced liver injury or discontinuations due to heart failure or edema6
Conclusions
Sparsentan demonstrated5,6:
Superior reductions in proteinuria
Better preservation of kidney function that accrued year on year
A comparable safety profile with irbesartan
Projected eGFR data of sparsentan and irbesartan suggest prolonged kidney survival with sparsentan6
Related Content
Implementing the Kidney Health Initiative Surrogate Efficacy Endpoint in Patients With IgA Nephropathy (the PROTECT Trial)
Kidney International Reports – 2019
IgA Nephropathy Patient Baseline Characteristics in the Sparsentan PROTECT Study
Kidney International Reports – 2023
Sparsentan in Patients With IgA Nephropathy: A Prespecified Interim Analysis From a Randomised, Double-Blind, Active-Controlled Clinical Trial
The Lancet – 2023
Footnotes
*Participants were enrolled between December 2018 and May 2021.6 †Includes related terms.5 ‡Elevations in ALT or AST greater than 3-fold ULN.5
AE, adverse event; ALT, alanine aminotransferase; Ang II, angiotensin II; AST, aspartate aminotransferase; AT1R, angiotensin II subtype 1 receptor; DEARA, Dual Endothelin Angiotensin Receptor Antagonist; eGFR, estimated glomerular filtration rate; ET-1, endothelin 1; ETAR, endothelin type A receptor; FDA, Food and Drug Administration; IgA, immunoglobulin A; ULN, upper limit of normal; UPCR, urine protein-creatinine ratio.
- Kwon CS et al. J Health Econ Outcomes Res. 2021;8(2):36-45.
- Pitcher D et al. Clin J Am Soc Nephrol. 2023;18(6):727-738.
- Martínez-Díaz I et al. Int J Mol Sci. 2023;24(4):3427.
- Komers R, Plotkin H. Am J Physiol Regul Integr Comp Physiol. 2016;310(10):R877-884.
- FILSPARI® (sparsentan) Prescribing Information. San Diego, CA: Travere Therapeutics, Inc. August 2025.
- Rovin BH et al. Lancet. 2023;402(10417):2077-2090.
- Heerspink HJL et al. Lancet. 2023;401(10388):1584-1594.
MA-SP-24-0049 | November 2024