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PROTECT Post Hoc Analysis: Efficacy of Sparsentan vs Irbesartan in Patients With IgA Nephropathy ≤12 mo vs >12 mo From Kidney Biopsy

Poster
Published on November 7, 2025

Topics: Nephrology IgAN Sparsentan PROTECT Clinical Poster Presentation Summary

Contributors
Wadhwani S, Barratt J, Komers R et al.


Presented at:
ASN 2025


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Home » PROTECT Post Hoc Analysis: Kidney Biopsy

About the research

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Summary

Background

  • In IgA nephropathy, upregulation of endothelin-I (ET-1) and angiotensin II (Ang II) can amplify ongoing kidney injury through mesangial cell activation, inflammatory cytokine release, and interstitial fibrosis, ultimately leading to nephron loss.1,2
  • Early diagnosis and prompt treatment of IgA nephropathy is essential, as nephron loss may have already occurred by time of diagnosis.1,3 The KDIGO 2025 IgAN Guideline recommends beginning treatment when proteinuria is ≥0.5 g/day.1,3
  • Sparsentan is a non-immunosuppressive Dual Endothelin Angiotensin Receptor Antagonist (DEARA) indicated to slow kidney function decline in adults with primary IgA nephropathy who are at risk for disease progression.1,2,4,5
  • In the Phase 3 PROTECT trial, sparsentan showed superior proteinuria reduction and kidney function preservation vs. maximum labeled dose irbesartan with a comparable safety profile.6
  • While sparsentan was favored vs. irbesartan across multiple prespecified subgroups in the PROTECT trial,7 it is not known whether time from biopsy to informed consent affects efficacy of sparsentan.1

Aim

To assess whether time from biopsy to informed consent in the PROTECT trial affects proteinuria reduction and estimated glomerular filtration rate (eGFR) preservation with sparsentan vs. irbesartan.1


Approach

PROTECT was a large, international, randomized, double-blind, active controlled Phase 3 trial to assess the efficacy and safety of sparsentan (n=202) vs. maximum labeled irbesartan (n=202).1,6

This post hoc analysis assessed the efficacy of sparsentan vs. irbesartan in patients with recent biopsies (≤12 months between time of biopsy and time of informed consent) vs. older biopsies (>12 months).1


Key findings

The median (interquartile range [IQR]) time from initial kidney biopsy to informed consent trial was 4.0 years (Range: 1.0 to 10.0).1

Ninety-one patients had recent biopsies, and 313 patients had older biopsies.1

Regardless of time from biopsy, patients treated with sparsentan achieved complete remission (CR) of proteinuria (urine protein excretion [UPE] <0.3 g/day) more frequently than those treated with irbesartan1:

  • ≤12 months from biopsy: 39.0% sparsentan vs. 14.0% irbesartan
  • 12 months from biopsy: 28.6% sparsentan vs. 10.5% irbesartan

In both groups, sparsentan showed rapid and greater urine protein-to-creatinine ratio (UPCR) reductions vs. irbesartan, which were sustained through Week 1101:

  • ≤12 months from biopsy: 43% reduction
  • 12 months from biopsy: 41% reduction

Estimates of UPCR percent change at Week 110 across different durations of time from biopsy demonstrated that treatment with sparsentan achieved consistent and greater proteinuria reduction vs. irbesartan.

Sparsentan showed slower rates of eGFR decline than irbesartan for both chronic* and total slope†1:

  • Chronic slope
    • ≤12 months from biopsy: −2.2 sparsentan vs. −3.7 irbesartan (Difference, 95% CI: 1.5, −1.4 to 4.3)
    • 12 months from biopsy: −3.0 sparsentan vs. −4.0 irbesartan (Difference, 95% CI: 1.0, (−0.01 to 1.98)
  • Total slope
    • ≤12 months from biopsy: −2.3 sparsentan vs. −3.6 irbesartan (Difference, 95% CI: 1.3, −1.4 to 4.1)
    • 12 months from biopsy: −3.2 sparsentan vs. −4.0 irbesartan (Difference, 95% CI: 0.9, −0.1 to 1.9)

Conclusions

Regardless of time from biopsy, sparsentan showed greater efficacy than irbesartan, with greater proteinuria reduction and preservation of kidney function seen with shorter time from biopsy.1

These results support recommendations from the KDIGO 2025 IgAN Guideline, highlighting the need for early diagnosis and suggesting early initiation of sparsentan treatment.1,3





Related Content

Posters Nephrology IgAN

PROTECT Subgroup Analysis: Sparsentan Provides Clinical Benefits vs Irbesartan in Patients With IgA Nephropathy With Proteinuria Above and Below 1 g/g

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Posters Nephrology IgAN

Impact of Histology on Efficacy of Sparsentan Therapy in IgA Nephropathy: Central Biopsy Review of Patients in the PROTECT Trial

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Posters Nephrology IgAN

Implications of Proteinuria Remission on Estimated Glomerular Filtration Rate Trajectory in Patients With IgA Nephropathy in PROTECT

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Footnotes

*Measured from Week 6 to 110.1

†Measured from Day 1 to Week 110.1

Ang II, angiotensin II; CI, confidence interval; CR, complete remission; DEARA, Dual Endothelin Angiotensin Receptor Antagonist; eGFR, estimated glomerular filtration rate; ET-1, endothelin-I; IgA, immunoglobulin A; IQR, interquartile range; UPCR, urine protein-to-creatinine ratio; UPE, urine protein excretion.

  1. Wadhwani S et al. Poster presented at: American Society of Nephrology Kidney Week 2025; November 6-9, 2025; Houston, TX. FR-PO0807.
  2. Kohan DE et al. Clin Sci (Lond). 2024;138(11):645-662.
  3. Kidney Disease: Improving Global Outcomes 2025 Clinical Practice Guidelines (IgAN/IgAV). 2025;108(4S):1-71.
  4. FILSPARI® (sparsentan) Prescribing Information. San Diego, CA: Travere Therapeutics, Inc.
  5. FILSPARI® (sparsentan) Summary of Product Characteristics. Paris, France: Vifor France.
  6. Rovin BH et al. Lancet. 2023;402(10417):2077-2090.
  7. Heerspink HJL et al. Lancet. 2023;401(10388):1584-1594.


MA-SP-25-0214 | November 2025