Slide 1: Sparsentan As First-Line Treatment of Incident Patients With IgAN: Interim Analysis of the SPARTAN Trial
FR-OR63 Sparsentan As First-Line Treatment of Incident Patients With IgA Nephropathy (IgAN): To obtain a PDF of this oral, please Interim Analysis of the scan the Quick Response (QR) code. No personal SPARTAN Trial information is stored. A visual summary of this presentation is accessible via the QR
Slide 2: Disclosures
DISCLOSURES • CKC has received consulting fees and research funding from Travere Therapeutics, Inc. • SM is an employee and stockholder of Travere Therapeutics, Inc. • ND and JB have received consulting fees and research funding from Travere Therapeutics, Inc. • SG has received consulting fees from
Slide 3: Introduction
INTRODUCTION • Sparsentan, a non-immunosuppressive novel dual endothelin and angiotensin receptor antagonist (DEARA), is approved in the US and the EU to treat adults with IgAN based on data from the Phase 3 PROTECT trial1-4 Sparsentan targets glomerular injury and slows kidney function decline1,5 E
Slide 4: Introduction
INTRODUCTION • In the PROTECT trial, sparsentan showed reduced proteinuria and long- term kidney function preservation in prevalent IgAN patients vs maximally titrated irbesartan1,2 • The effect in newly diagnosed, RASi-naive patients remains unknown • SPARTAN (NCT04663204) is a Phase 2, open-label,
Slide 5: Methods
METHODS SPARTAN Study Design (NCT04663204) • The SPARTAN study is being conducted at 5 participating sites in the UK Day 1 to week 2 Week 3 to 110 Week 110 to 114 Screening SPAR SPAR Follow-up 200 mg 400 mg N=12 Start SOC RASi therapy Treatment period, weeks Final visit Key Eligibility Criteria • Ag
Slide 6: Demographics and Baseline Characteristics of Patients in SPARTAN vs PROTECT
RESULTS Demographics and Baseline Characteristics of Patients in the SPARTAN vs PROTECT Trials SPARTAN PROTECT1,2 (N=12) (N=402) RASi use, % 0* >99† IST use, % 0‡ 5§ Time from initial kidney biopsy to informed consent, 0.25 (0.14-0.39)║ 4.0 (1.0-10.0) median (IQR), years Age at informed consent, mea
Slide 7: Proteinuria Change (UPCR) From Baseline
RESULTS Proteinuria Change (UPCR) From Baseline* • Proteinuria reductions were rapid (≈60% from baseline at week 4) and sustained over 24 weeks of sparsentan treatment 0 Median (IQR) UPCR at baseline (n=12): Change in UPCR from baseline, 1.3 (0.4-1.7) g/g geometric mean (SE), % −20 Median (IQR) UPCR
Slide 8: Proteinuria Per Individual Patient
RESULTS Proteinuria Per Individual Patient* • Among the 5 patients with protein excretion of >2 g/day at baseline, 4 had proteinuria reductions of ≥75% at any time during the first 24 weeks of treatment • 58% of patients (7/12) achieved complete remission (<0.3 g/day) at any time during the 24-week
Slide 9: Mean eGFR at Each Visit Over Weeks
RESULTS Mean eGFR at Each Visit Over 24 Weeks* 100 eGFR, mean (SD), mL/min/1.73 m2 90 80 70 60 50 40 30 20 10 n=12 n=12 n=11 n=12 n=11 n=11 0 -2 0 2 4 6 8 10 12 14 16 18 20 22 24 Week Week *On-treatment analysis; 1 patient discontinued after week 6. 9
Slide 10: Mean Office BP at Each Visit Over Weeks
RESULTS Mean Office BP at Each Visit Over 24 Weeks* • After an initial slight decrease, BP remained stable during the rest of the treatment period as measured by office and ambulatory BP 160 SBP DBP 140 BP, mean (SD), mm Hg 120 100 80 60 40 20 n=12 n=12 n=11 n=12 n=11 n=11 0 -2 0 2 4 6 8 10 12 14 16
Slide 11: Mean Weight and Total Body Water Change From Baseline
RESULTS Mean Weight and Total Body Water Change From Baseline* • There were no meaningful changes in body weight over 24 weeks • Mean total body water change from baseline showed modest reductions during the treatment period Week Mean (SD) change from baseline 2 4 6 12 24 n 12 11 12 11 11 Weight, kg
Slide 12: Safety Over Weeks of Treatment
RESULTS Safety Over 24 Weeks of Treatment • Sparsentan was generally well tolerated • 1 patient permanently discontinued treatment due to hypotension after week 6 Sparsentan (N=12) n (%) Any AE 12 (100) Any serious AE* 1 (8) Most common AEs (>2 patients) Dizziness 6 (50) Urinary tract infection 3 (2
Slide 13: Urinary sCD163 Levels
RESULTS Urinary sCD163 Levels* • Urinary sCD163 (u-sCD163) is a marker for alternatively activated macrophages that has been correlated with kidney macrophage infiltration and active lesions in IgAN. In the TESTING study, a ≥50% reduction of u-sCD163 from baseline was associated with a reduced risk
Slide 14: Kidney Biopsy Single-Cell Nuclear RNA-seq Gene Expression Profile
Kidney Biopsy Single-Cell Nuclear RNA-seq Gene Expression RESULTS Profile to Define the Impact of Sparsentan on Kidney Cell Populations 14
Slide 15: Conclusions
CONCLUSIONS These interim findings from the SPARTAN trial show that sparsentan, as a first-line treatment in patients with IgAN, led to rapid and sustained reductions in proteinuria (~70% from baseline) Within 24 weeks of starting sparsentan, ~60% of patients achieved complete remission of proteinur
Slide 16: Acknowledgments
ACKNOWLEDGMENTS • This study was funded by Travere Therapeutics, Inc. • Urinary biomarker analysis was provided by: • Nadia Nawaz and William Barratt, University of Leicester • Transcriptomics analysis was provided by: • Professor Matthias Kretzler, University of Michigan • Francesca Annese, Brad Go
Slide 17: Questions?
Questions? Leicester gine Research Group UNIVERSITY OF LEICESTER