Preliminary Data from SPARTAN Trial Presented at ASN 2023

Jonathan Barratt, MD

Credit: IgA Nephropathy Foundation

Preliminary findings from the SPARTAN trial assessing the safety and efficacy of sparsentan showed the treatment was safe and well-tolerated as a first-line therapy in patients with newly diagnosed immunoglobulin A nephropathy (IgAN).

Data through 12 weeks of treatment in the open-label, single-arm, multi-center, exploratory trial was presented at the American Society of Nephrology Kidney Week 2023, providing an overview of sparsentan’s impact on proteinuria and total body water over time.¹

“We're looking at how this drug achieves kidney protection, and so within that we have a range of biomarker measures to look at what actually is changing fundamentally in the kidney in terms of pathways that are impacted by sparsentan,” said Jonathan Barratt, MD, Mayer Professor of Renal Medicine at the University of Leicester, in an interview with HCPLive Nephrology.

A non-immunosuppressive, single molecule dual endothelin angiotensin receptor antagonist, sparsentan selectively target 2 critical pathways in the disease progression of IgAN: endothelin-1 and angiotensin 2. It is the first and only non-immunosuppressive therapy approved for the treatment of this condition, receiving an indication from the US Food and Drug Administration granted under accelerated approval on February 17, 2023.²

The decision was based on clinically meaningful and statistically significant improvements in proteinuria among patients taking sparsentan compared to irbesartan in the phase 3 PROTECT study. In addition to sparsentan’s ability to reduce proteinuria, new PROTECT data presented at ASN Kidney Week 2023 revealed its potential to significantly delay time to kidney failure.²

For inclusion in the SPARTAN study, patients were required to be ≥18 years of age with biopsy-proven IgAN diagnosed within 6 months of enrollment, proteinuria ≥0.5 g/d, eGFR ≥30 ml/min/1.73m2 at screening, and no previous treatment with ACEis/ARBs within the past 12 months.¹

Participants will receive sparsentan for 110 weeks with 4-week safety follow-up. Safety, proteinuria, estimated and measured GFR, 24h ambulatory blood pressure (BP), and total body water were monitored and reported through 12 weeks of treatment in a preliminary analysis.¹

At data cutoff on May 4, 2023, 6 participants had received ≥1 dose of sparsentan with 12 weeks of follow-up. The mean age at enrollment was 42 (Standard deviation [SD], 14) years and 4 patients were female. At baseline, median proteinuria was 1.4 (interquartile range [IQR], 0.6-2.0) g/d, mean eGFR was 67 (SD, 27) ml/min/1.73m2, and systolic/diastolic BP was 122/80 (SD, 7/6) mmHg.¹

From baseline to week 12, total body water decreased from 47 (SD, 4) l to 44 (SD, 9) l. By week 12, 33% (n = 2) of participants achieved complete remission of proteinuria, defined as <0.3 g/d. Among the cohort, sparsentan reduced proteinuria by 71.4% over 12 weeks.¹

“The highly detailed examination of the kidney biopsy is what we’ll be coming to next year, because we still need some of our patients to get through to those later time points. So this is just a very eagle-eyed look at what we're doing in SPARTA with the prelude that we're going to be doing far more and presenting far more exciting data over the next 12 to 24 months,” Barratt concluded.

References:

1. Cheung CK, Burns C, Dhaun N, et al. Sparsentan as First-Line Treatment of Incident Patients with IgA Nephropathy: Preliminary Findings from the SPARTAN Trial. Paper Presented at: American Society of Nephrology Kidney Week 2023. November 1-5, 2023.
2. Travere Therapeutics. Travere Therapeutics Announces FDA Accelerated Approval of FILSPARIᵀᴹ (sparsentan), the First and Only Non-immunosuppressive Therapy for the Reduction of Proteinuria in IgA Nephropathy. February 17, 2023. Accessed November 7, 2023. https://ir.travere.com/news-releases/news-release-details/travere-therapeutics-announces-fda-accelerated-approval