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.

In this episode, Drs. Tobias Huber and Chris Gisler take a deep dive into the critical role of podocytes in kidney health and their involvement in the development and progression of FSGS. They explore how podocyte injury leads to the breakdown of the glomerular filtration barrier and the emergence of proteinuria. They highlight the intertwined roles of endothelin 1 and angiotensin II in worsening podocyte dysfunction and driving disease progression. They discuss current and emerging data, treatment options, and biomarkers, including findings from Dr. Huber’s latest research. Lastly, they emphasize the value of proteinuria as both a marker and mediator of podocyte damage, reinforcing its role as a key therapeutic target in FSGS.

Key Takeaways:

• Podocytes are essential for maintaining the integrity and health of the kidney.
• Podocyte damage directly contributes to proteinuria and disease progression.
• Proteinuria is both a symptom and a driver of FSGS disease progression.
• Endothelin 1 and angiotensin II promote podocyte dysfunction.

Speakers:

• Tobias Huber is the Chair of the Center of Internal Medicine at University Medical Center Hamburg-Eppendorf, Germany and president of the International Society of Glomerular Disease.
• Chris Gisler is a medical director at Travere Therapeutics and a community nephrologist practicing in Pittsburgh.

Title: Intro to FSGS

Episode Description: In this episode of the Rare Kidney Disease Show, Howard Trachtman, Adjunct Professor of Pediatrics at the University of Michigan, and Chris Gisler, medical director at Travere Therapeutics, explore the complexities of FSGS, covering its pathophysiology, classifications, and clinical presentation. They discuss key drivers of kidney failure, challenges in diagnosis and management, and the unmet need for safe and effective treatments. Listeners will gain insights into the patient journey, role of precision medicine, disease heterogeneity, and the future of clinical trial design. The episode concludes with how PARASOL is shaping advancements in FSGS research and clinical trials.

Key Takeaways:

• Evolving Classification of FSGS – Once defined primarily by histopathology, FSGS is now recognized as a heterogeneous disorder with distinct genetic, immune, and metabolic etiologies. This shift has critical implications for diagnosis and treatment.
• FSGS and the Role of Podocyte Injury – Podocyte loss is a key driver of FSGS progression, with genetic, immune, and metabolic insults leading to irreversible damage. Understanding this mechanism is crucial for developing targeted therapies.
• Challenges in Treatment and Therapeutic Gaps – Current treatment strategies rely on empiric use of steroids and calcineurin inhibitors, with variable efficacy and significant side effects. A more targeted approach is needed to improve patient outcomes.

Speakers:

• Howard Trachtman is the Adjunct Professor of Pediatrics at the University of Michigan.
• Chris Gisler is a medical director at Travere Therapeutics and a former community nephrologist practicing in Pittsburgh.