Trial data of sparsentan in the treatment of IgA nephropathy?

A trial of sparsentan in the treatment of IgA nephropathy

Sparsentan, a novel, nonimmunosuppressive, single-molecule, dual endothelin-angiotensin receptor antagonist, produced a significant reduction in proteinuria at 36 weeks (the primary endpoint) in patients with immunoglobulin A nephropathy compared with the angiotensin II receptor blocker irbesartan in a previously reported interim analysis of the phase 3 PROTECT trial. Here, renal function and outcomes at 110 weeks in a double-blind final analysis are reported.

research methods

PROTECT was a double-blind, randomized, active-controlled Phase 3 study (NCT03762850) conducted at 134 clinical practice sites in 18 countries. The patient is 18 years of age or older with biopsy-confirmed primary IgA nephropathy and proteinuria of at least 1-0 g per day despite maximal suppression of the renin-angiotensin system for at least 12 weeks. Patients were randomly assigned (1:1) to receive treatment with (target dose 400 mg oral sparsentan once daily) or irbesartan (target dose 300 mg oral irbesartan once daily) based on block randomization.

The primary endpoint was change in proteinuria in the treatment group at 36 weeks. Secondary endpoints included rate of change (slope) in estimated glomerular filtration rate (eGFR), change in proteinuria, a composite of renal failure (confirmed 40% decrease in eGFR, end-stage renal disease, or all-cause mortality), and safety and tolerability up to 110 weeks from randomization.

Research results

203 patients were randomly assigned to the sparsentan group, and 203 patients were randomly assigned to the irbesartan group. Patients in the sparsentan group experienced a slower decline in eGFR compared with the irbesartan group. eGFR chronic 2-year slope (weeks 6-110) was -2-7 mL/min per 1-73 m2 per year vs -3-8 mL/min per 1-73 m2 per year (difference 1-1 mL/min per 1-73 m2 per year, 95% CI 0-1 to 2-1; p=0-037); overall 2-year slope (day 1-week 110 weeks) was -2-9 mL/min per 1-73 m2 per year versus -3-9 mL/min per 1-73 m2 per year (difference 1-0 mL/min per 1-73 m2 per year, 95% CI -0-03 to 1-94; p=0-058).

The significant reduction in proteinuria with sparsentan at 36 weeks was maintained throughout the study; at 110 weeks, proteinuria was 40% lower in the sparsentan group than in the irbesartan group, as determined by the change from baseline in the urinary protein to creatinine ratio (sparsentan, -42 to 8%; irbesartan, -4 to 4%, -15 to 8 to 8; geometric least squares mean ratio, 0 to 60).

Eighteen of 202 patients (9%) in the sparsentan group achieved the composite renal failure endpoint, compared with 26 of 202 patients (13%) in the irbesartan group (relative risk 0-7, 95% CI 0-4 to 1-2). The incidence of treatment flares was well balanced between the sparsentan and irbesartan groups, and no new safety signals emerged.

Test conclusion

During 110 weeks of treatment, patients with IgA nephropathy treated with sparsentan significantly reduced proteinuria and preserved renal function compared with maximal titration of irbesartan.

Sparsentan price

Sparsentan has not been launched in mainland China as of October 2023, and no price has been announced.

Currently, we know through domestic professional overseas medical service organizations (such as Medical Companion Travel) that the price of 400 mg x 30 tablets of Sparsentan is about $12,300 per box, but the price is not fixed due to various factors.

Patients in need can choose according to their own situation. They can buy it in areas where it is already on the market, or they can obtain it through domestic professional overseas medical service organizations (such as Medical Companion Travel). It can be mailed to their homes and is cost-effective. Please consult customer service personnel for specific costs and acquisition procedures.

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References

Rovin BH, Barratt J, Heerspink HJL, Alpers CE, Bieler S, Chae DW, Diva UA, Floege J, Gesualdo L, Inrig JK, Kohan DE, Komers R, Kooienga LA, Lafayette R, Maes B, Małecki R, Mercer A, Noronha IL, Oh SW, Peh CA, Praga M, Preciado P, Radhakrishnan J, Rheault MN, Rote WE, Tang SCW, Tesar V, Trachtman H, Trimarchi H, Tumlin JA, Wong MG, Perkovic V; DUPRO steering committee and PROTECT Investigators. Efficacy and safety of sparsentan versus irbesartan in patients with IgA nephropathy (PROTECT): 2-year results from a randomized, active-controlled, phase 3 trial. Lancet. 2023 Nov 2:S0140-6736(23)02302-4. doi: 10.1016/S0140-6736(23)02302-4. Epub ahead of print. PMID: 37931634.