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Abstract: FR-PO0805

Sparsentan Slows the Loss of Kidney Function in Patients with IgAN: Post Hoc Analyses of the Phase 3 PROTECT Study

Session Information

Category: Glomerular Diseases

  • 1402 Glomerular Diseases: Clinical, Outcomes, and Therapeutics

Authors

  • Roll, Matthias, Vifor Pharma Deutschland GmbH, Munich, BY, Germany
  • Hardt, Thomas, Vifor Pharma Deutschland GmbH, Munich, BY, Germany
  • Gladbach, Amadeus, Vifor Pharma Deutschland GmbH, Munich, BY, Germany
  • Floege, Jürgen, Universitätsklinikum Aachen, Med. Klinik II, Nephrologie u. Klinische Immunologie, Aachen, Germany
Background

Primary immunoglobulin A nephropathy (IgAN) is a rare immune-mediated glomerular disease, with a median age of diagnosis of around 40 years. Up to 40% of patients progress to end-stage renal disease within 20 years of diagnosis. Sparsentan (SPAR) is a novel dual endothelin-angiotensin receptor antagonist. This post -hoc analysis compares the efficacy of SPAR vs. irbesartan (IRB) in preventing the progression to chronic kidney disease (CKD) stages 4 or 5 and was conducted as part of the HTA process in Germany.

Methods

The randomized, double-blind, active-controlled, multicenter Phase III PROTECT study examined the efficacy and safety of SPAR (n=202) vs. maximum-dose IRB (n=202) in adult patients with biopsy-proven IgAN over 110 weeks. As a study inclusion criterion, patients had to have CKD stage 1-3 at screening. However, some patients progressed to CKD stage 4 prior to baseline visit (SPAR n=15, IRB n=5). Here we analyze the proportion of patients who progressed to CKD stages 4 or 5 by Week 110 and the time to reach CKD stages 4 or 5. The entire study population (CKD 1-4) as well as patients with CKD stages 1-3 at baseline (CKD 1-3) were analyzed.

Results

Statistically fewer patients treated with SPAR reached CKD stages 4 or 5 compared to IRB. Moreover, the time to reach CKD stages 4 or 5 was statistically significantly longer under SPAR treatment. This treatment benefit of SPAR was demonstrated for patients with CKD stages 1-4 as well as for patients with CKD stages 1-3 at baseline (Table 1).

Conclusion

This post hoc analysis confirms the effect of SPAR on the clinically relevant parameter eGFR: SPAR effectively slows down the loss of renal function compared to IRB. Statistically significantly fewer patients progress to CKD stages 4 or 5 under SPAR, and the time to reach CKD stages 4 or 5 is prolonged —an effect outcome that was accepted as patient-relevant in the German HTA process and led to an evidence-based additional benefit.

Table 1: Patients with CKD stages 4 or 5 until Week 110
CKD stage at baselineSPAR
n/N (%)
IRB
n/N (%)
Patients with CKD 4/5
RR [95% CI]
Patients with CKD 4/5
p value
Time to reach CKD 4/5
HR [95% CI]
Time to reach CKD 4/5
p value
CKD 1-447/202 (23.3)65/202 (32.2)0.731
[0.555, 0.964]
0.0260.666
[0.458, 0.971]
0.034
CKD 1-343/187 (23.0)65/197 (33.0)0.735
[0.558, 0.969]
0.0290.672
[0.457, 0.989]
0.044

Funding

  • Commercial Support – Vifor Pharma Deutschland GmbH

Digital Object Identifier (DOI)