How Sparsentan is Reshaping Care for Patients With FSGS, With George Vasquez Rios, MD

The April 2026 US Food and Drug Administration approval of sparsentan (Filspari) marked the first approved therapy specifically indicated for focal segmental glomerulosclerosis (FSGS), a rare glomerular disease associated with progressive kidney function decline and a substantial risk of kidney failure.

Supported by data from the phase 3 DUPLEX trial, the approval introduced a long-awaited treatment option for a disease area that has historically relied on supportive care and off-label immunosuppressive therapies. The approval has prompted important discussions among nephrologists about how to interpret proteinuria reduction, incorporate sparsentan into treatment algorithms, and identify the patients most likely to benefit from therapy.

To better understand these questions, HCPLive spoke with George Vasquez-Rios, MD, MSCR, FASN, nephrologist and glomerular disease specialist and director of the Glomerular & Genetic Diseases Center. In this Q&A, Vasquez-Rios discusses sparsentan's mechanism of action, the clinical significance of proteinuria reduction, and how the approval may reshape care for patients with FSGS.

HCPLive: For decades, FSGS has lacked an FDA-approved disease-specific therapy. How does the approval of sparsentan change the standard of care, and what does success now look like for these patients?

Vasquez-Rios, MD: In the past, FSGS has been managed with foundational therapies such as renin-angiotensin system blockade and, in cases of immune-mediated disease, immunosuppression to achieve meaningful reductions in proteinuria. With the addition of sparsentan to the treatment landscape, we now have another option to effectively reduce proteinuria and potentially modify disease progression.

Reductions in proteinuria have consistently been associated with improved kidney outcomes, so having a medication that can help us achieve those reductions without necessarily exposing patients to the adverse effects of immunosuppression is a major step forward for the management of FSGS.

HCPLive: Where do you see sparsentan fitting relative to current standard approaches such as RAS blockade and immunosuppressive therapy?

Vasquez-Rios: Sparsentan has the potential to take the place of traditional RAS blockade in many patients. Conventional therapies primarily target intraglomerular pressure, which is important for blood pressure control and reducing proteinuria.

However, sparsentan is a dual endothelin and angiotensin receptor antagonist, meaning it targets 2 important mechanisms. In addition to addressing intraglomerular pressure, it also affects podocyte biology. Podocytes express endothelin receptors, and excessive activation of these pathways contributes to oxidative stress, inflammation, fibrosis, and ultimately proteinuria.

By targeting both pathways simultaneously, sparsentan offers a unique mechanism that addresses key drivers of kidney injury in FSGS.

HCPLive: How should clinicians think about sparsentan's dual endothelin and angiotensin pathway inhibition in the context of FSGS biology?

Vasquez-Rios: FSGS is a syndrome rather than a single disease and includes multiple subtypes, including primary, genetic, and secondary forms. Regardless of the underlying cause, podocyte injury is a central feature of disease progression.

The fact that sparsentan reduces proteinuria while also helping preserve kidney function is very attractive. That said, it should not replace immunosuppressive therapies in patients with primary FSGS, where immune dysregulation remains a key component of disease biology.

Instead, sparsentan can serve as an important foundational therapy that clinicians can initiate early while evaluating patients and making decisions regarding additional treatments.

HCPLive: In the phase 3 DUPLEX trial, sparsentan did not meet its primary endpoint for eGFR decline. How are clinicians interpreting that result alongside the proteinuria reductions observed in the study?

Vasquez-Rios: The DUPLEX trial represented an important milestone for FSGS research. One of the challenges is that FSGS is an extremely heterogeneous condition. Even with careful evaluation, it can be difficult to distinguish primary, genetic, and secondary forms of disease, and each subgroup may follow a different clinical trajectory.

As a result, capturing meaningful differences in long-term eGFR outcomes across a heterogeneous patient population can be difficult. We also need to consider the acute hemodynamic effects of treatment separately from chronic eGFR slope effects. When both are analyzed together, there is the potential to underestimate the long-term clinical benefit of a therapy.

Importantly, open-label extension data have demonstrated that patients who achieved early proteinuria reductions with sparsentan experienced better long-term kidney outcomes. Programs such as PARASOL have also helped improve our understanding of clinically meaningful endpoints in FSGS and contributed to the FDA's recognition of proteinuria reduction as an important therapeutic target.

HCPLive: Which patients with FSGS are most likely to benefit from sparsentan?

Vasquez-Rios: Patients with persistent proteinuria despite standard therapies are among the most likely to benefit. Many patients remain above target proteinuria levels despite treatment with RAS blockade, SGLT2 inhibitors, and other interventions.

Some patients are also unable to tolerate combinations of therapies because of blood pressure limitations. In those situations, sparsentan offers an opportunity to achieve meaningful proteinuria reduction through dual pathway inhibition while potentially reducing treatment burden.

Patients with primary FSGS may benefit as part of a broader treatment strategy, and emerging evidence also suggests benefit in patients with genetic forms of FSGS. Overall, I think sparsentan should be considered across a broad range of patients with proteinuric FSGS.

HCPLive: Is there anything else clinicians should keep in mind following the approval of sparsentan?

Vasquez-Rios: FSGS remains a challenging condition that requires careful clinical evaluation to determine the underlying mechanism of disease. Patients with primary, immune-mediated FSGS often present with abrupt-onset proteinuria and may require immunosuppressive therapy. Other patients may have a more gradual decline in kidney function suggestive of secondary or genetic disease.

A detailed clinical history remains essential. Beyond establishing foundational therapies, including sparsentan, clinicians should focus on identifying the underlying disease process and intervening early to modify long-term outcomes.

The advances we've seen through PARASOL and other research efforts have improved our understanding of meaningful treatment targets in FSGS. While additional evidence continues to emerge, incorporating therapies that effectively reduce proteinuria and stabilize kidney function is an important step toward improving outcomes for these patients.

Editor’s Note: Vasques Rios reports no relevant disclosures.

References

1. Hillenbrand A. FDA Approves Sparsentan for Focal Segmental Glomerulosclerosis. HCPLive. Published April 13, 2026. Accessed June 1, 2026. https://www.hcplive.com/view/fda-approves-sparsentan-for-focal-segmental-glomerulosclerosis

2. Rheault MN, Alpers CE, Barratt J, et al. Sparsentan versus Irbesartan in Focal Segmental Glomerulosclerosis. The New England Journal of Medicine. 2023;389(26). doi:https://doi.org/10.1056/nejmoa2308550