Presentation (CTI)

OBJECTIVES: Immunoglobulin A nephropathy (IgAN) is a rare kidney disease with poor prognosis and high unmet medical need. Sparsentan is the first EMA approved non-immunosuppressive therapy for IgAN. Sparsentans positive effects on proteinuria and estimated glomerular filtration rate are clinically relevant. However, those biochemical endpoints are not recognized as patient relevant in the German HTA process. Here we demonstrate that sparsentan prevents patients from entering the chronic kidney disease (CKD) stages 4 or 5. A post hoc analyses that led to the recognition of an evidence based “additional benefit” in Germany’s HTA.
METHODS: The RCT PROTECT examined the efficacy and safety of sparsentan (n=202) vs. maximum labeled dose Irbesartan (n=202) in adult patients with biopsy-proven IgAN over 110 weeks. For study inclusion patients had to have CKD stage 1-3 at screening. However, some patients progressed to CKD stage 4 prior to baseline visit (sparsentan: n=15; irbesartan: n=5). We analyzed the progression to CKD stages 4 or 5 of the overall study population (CKD 1-4) and of patients with CKD stages 1-3 at baseline (CKD 1-3).
RESULTS: Significantly fewer patients treated with sparsentan progressed to CKD stages 4 or 5 compared to irbesartan (CKD 1-4 at baseline: 23.3% vs. 32.2%, RR [95%-CI] = 0.731 [0.555; 0.964], p=0.026; CKD 1-3 at baseline: 23.0% vs. 33.0%, RR [95%-CI]=0.735 [0.558; 0.969], p=0.029). The time to reach CKD stages 4 or 5 was significantly longer with sparsentan (CKD 1-4 at baseline: HR [95% CI] =0.666 [0.458; 0.971], p=0.034; CKD 1-3: HR=0.672 [0.457; 0.989], p=0.044).
CONCLUSIONS: Sparsentan significantly slowed renal function decline, reducing progression to CKD stages 4 or 5. These findings underscore the overall RCT and the importance of clinically relevant endpoints. The German HTA process should consider surrogate endpoints for CKD as patient relevant as they reflect critical diagnostic and prognostic indicators to derive an additional benefit.