In this episode, Drs. Jonathan Barratt and Shikha Wadhwani discuss findings from the SPARTAN study, a Phase 2 open-label, single-arm trial evaluating sparsentan in 12 treatment-naïve patients with IgA nephropathy. The conversation explores the trial’s design, including assessments of proteinuria reduction and urinary biomarkers to better understand sparsentan’s mechanism of action.

Results from SPARTAN demonstrate a 69% mean reduction in proteinuria at 24 weeks, alongside biomarker trends consistent with decreased glomerular inflammation. 

Dr. Barratt notes that no new safety signals emerged, with hypotension observed at a rate consistent with prior studies and no adverse hepatic events reported.

Together, the experts reflect on how these data support the biological plausibility of sparsentan’s anti-inflammatory properties and may inform the development of biomarker-guided strategies in IgA nephropathy, including ongoing evaluation of sparsentan in the PROTECT trial.

 Key Takeaways:

• SPARTAN demonstrated a robust mean reduction in proteinuria (~69%) in treatment-naïve patients with IgA nephropathy after 24 weeks of sparsentan therapy.
• Biomarker analysis revealed reductions in markers of macrophage activation, complement activity, and inflammatory cytokines, supporting the hypothesis of a potential anti-inflammatory effect.
• No new safety signals were observed; hypotension rates were consistent with earlier trials, and no clinically significant changes in hepatic function were reported.
• These findings contribute to our mechanistic understanding of sparsentan and provide a framework for future investigation of biomarkers from samples from larger studies such as PROTECT.

Speakers:  

• Dr. Jonathan Barratt, PhD, FRCP. Professor of Renal Medicine at the University of Leicester, where he leads the IgA Nephropathy Research Programme. He is internationally recognized for his leadership in translational and clinical research in glomerular diseases, particularly IgA nephropathy. Dr. Barratt directs the UK’s Rare Disease Group for the UK National Registry of Rare Kidney Diseases (RaDaR).
• Dr. Shikha Wadhwani, MD, MS, FASN. Associate Professor of Medicine in the Division of Nephrology and Vice Chair of Clinical Research in the Department of Medicine at University of Texas Medical Branch. She is also the inaugural Associate Research Officer for clinical research, overseeing clinical trials across all 5 schools at UTMB. She is the founding member of the International Society of Glomerular Disease (ISGD) and is steering a global effort aimed at supporting the growth and success of physician-trialists. In her spare time, Dr. Wadhwani co-hosts a podcast called Kidney Compass: Navigating Clinical Trials.  

Disclaimer: 

Guest speakers of the Rare Kidney Disease Show may be paid consultants of Travere Therapeutics. This podcast episode was recorded on July 25, 2025. Please always consult updated sources for the latest information, as information discussed may have changed since the recording date.