FILSPARI (sparsentan) - Primary immunoglobulin A nephropathy (IgAN)

The Committee deems that the clinical benefit of FILSPARI 200 mg and 400 mg film-coated tablets is low, as monotherapy, in the treatment of adults with primary immunoglobulin A nephropathy (IgAN) with a urine protein excretion ≥1.0 g/day (or urine protein-to-creatinine ratio ≥ 0.75 g/g), following an inadequate response to optimised standard of care with an ACE inhibitor or ARB.

Considering:

• the partially met medical need in patients with primary immunoglobulin A nephropathy (IgAN) with a urine protein excretion ≥1.0 g/day (or urine protein-to-creatinine ratio ≥ 0.75 g/g);
• the results of the randomised, double-blind, phase 3 PROTECT study conducted in adults with primary immunoglobulin A nephropathy (IgAN) with a urine protein excretion ≥1.0 g/day despite optimised treatment with an ACE inhibitor or ARB, which demonstrated the superiority of sparsentan compared to irbesartan for the primary endpoint assessing the urine protein/creatinine (UP/C) ratio, with a clinically relevant effect size (change of -40.77% in the sparsentan group versus -15.05% in the irbesartan group, p < 0.001);

but taking into account:

• the heterogeneous results observed for the secondary endpoints, with control of the alpha risk, assessing the change in eGFR over different periods and showing a significant difference, but of low clinical relevance (difference of 1.1 mL/min/1.73 m2), only for the annualised chronic slope of the eGFR change between weeks 6 and 110 (not taking into account initial haemodynamic effects related to treatment initiation), whereas eGFR is the most relevant biological endpoint to assess kidney function; 
• the absence of long-term data concerning recourse to dialysis or kidney transplant to confirm the efficacy of sparsentan on the decline in kidney function in the absence of clear evidence on the change in eGFR;
• the lack of evidence of an impact on quality of life;
• the absence of data in patients not previously treated with the standard of care;
• the lack of comparative data enabling the role of sparsentan to be determined compared to an SGLT-2 inhibitor (dapagliflozin) due to their concomitant development in this indication (data comparing sparsentan with the sparsentan plus SGLT-2 inhibitor combination are expected);
• the safety profile of sparsentan, comparable to that of irbesartan, but with, in particular, hepatic and renal risks requiring specific monitoring during treatment and meaning that sparsentan cannot be recommended in severe forms of renal or hepatic impairment;
• uncertainties with respect to the safety of sparsentan in patients with heart failure or severe hepatic impairment, following kidney transplant, and during breastfeeding, along with its contraindication during pregnancy;
• the numerous interactions with other medicinal products, limiting its use, particularly with angiotensin receptor blockers (ARBs), endothelin receptor antagonists (AREs) and renin inhibitors (contraindication);

the Committee deems that FILSPARI 200 mg and 400 mg film-coated tablets provide no clinical added value (CAV V) in the current care pathway for adults with primary immunoglobulin A nephropathy (IgAN) with a urine protein excretion ≥1.0 g/day (or urine protein-to-creatinine ratio ≥ 0.75 g/g), which includes relevant comparators (ACE inhibitors, ARBs, SGLT-2 inhibitor).