Drug Update · Nephrology

FDA Approves Sparsentan for FSGS Without Nephrotic Syndrome: 29% Proteinuria Reduction in DUPLEX Non‑Nephrotic Subgroup

September 03, 2026

Drug

sparsentan (FILSPARI)

Indication

Reduce proteinuria in adults and pediatric patients aged 8 years and older with FSGS without nephrotic syndrome

Primary efficacy result

29% proteinuria reduction in non‑nephrotic DUPLEX subgroup (95% CI: 8% to 44%)

Supporting trial

DUPLEX (randomized, double‑blind, active‑controlled phase 3)

Patients randomized (DUPLEX)

371

Approval date

2026-04-13

REMS

FILSPARI REMS required for hepatotoxicity

Dosing (FSGS)

>50 kg: 400 mg once daily for 14 days then 800 mg once daily; ≤50 kg: 200 mg once daily for 14 days then 400 mg once daily

Clinical Perspective

The approval affects nephrologists, pediatric nephrologists, and pharmacists caring for patients aged 8 years and older with biopsy‑proven FSGS who do not have nephrotic syndrome, offering an FDA‑labeled option to reduce proteinuria in this population ^[1]^[3]^[6]. The available randomized data from DUPLEX demonstrate a 29% estimated proteinuria reduction versus irbesartan in non‑nephrotic patients, supporting use where proteinuria reduction is a therapeutic goal and when REMS enrollment and monitoring can be ensured ^[5]^[6]^[2]. Clinicians must follow REMS enrollment, avoid coadministration with ARBs/ERAs/aliskiren, and implement required liver testing and contraception counseling for patients who can become pregnant ^[1]^[2].

Dr. Praveen Singh, MBBS, MD (General Medicine), DM (Nephrology) · Nephrology

The FDA approved a supplemental indication for FILSPARI (sparsentan) to reduce proteinuria in adult and pediatric patients aged 8 years and older with focal segmental glomerulosclerosis (FSGS) without nephrotic syndrome, effective April 13, 2026 ^[2]^[1]^[6]. The approval was supported by randomized data from the phase 3 DUPLEX study showing a larger proteinuria treatment effect in patients without nephrotic syndrome, with an estimated 29% reduction in proteinuria (95% CI: 8% to 44%) versus irbesartan in that subgroup ^[5]^[6].

Clinical Context

Sparsentan (FILSPARI) is a single-molecule oral antagonist of the endothelin type A receptor and the angiotensin II type 1 receptor, developed and marketed by Travere Therapeutics ^[6]^[1]. The new approval adds an FSGS label for patients 8 years and older without nephrotic syndrome and represents an FDA‑approved pharmacologic option for this FSGS subgroup; the FDA stated this is the first FDA‑approved treatment for patients with FSGS in this population ^[3]. Because of hepatotoxicity risk, FILSPARI is available only through a REMS program and requires baseline and ongoing liver monitoring per the prescribing information ^[1]^[2].

Key Findings

The DUPLEX randomized, double-blind, active‑controlled phase 3 trial compared sparsentan with irbesartan in patients with biopsy‑proven FSGS and UPCR ≥1.5 g/g. In the subgroup of patients without nephrotic syndrome, sparsentan produced an estimated 29% reduction in proteinuria versus irbesartan (95% CI: 8% to 44%) ^[5]^[6].
The FDA reviewers noted that DUPLEX did not meet its prespecified eGFR‑based primary endpoint at final analysis in the overall trial population, but concluded that the totality of evidence supported effectiveness for reducing proteinuria in the indicated non‑nephrotic FSGS population ^[5]^[2].
The approval specifies use in adults and pediatric patients aged 8 years and older with FSGS without nephrotic syndrome and explicitly excludes coadministration with ARBs, ERAs, or aliskiren per labeling ^[1]^[2].

Safety & Tolerability

Hepatotoxicity: FILSPARI carries a boxed warning for hepatotoxicity and embryo‑fetal toxicity and is available only through the FILSPARI REMS because of hepatotoxicity risk; measure aminotransferases and bilirubin before initiation and ALT and AST every 3 months during treatment ^[1]^[2].
Peripheral edema ^[1].
Hypotension, including orthostatic hypotension ^[1].
Hyperkalemia ^[1].
Dizziness ^[1].
Anemia ^[1].
Acute kidney injury and elevations in aminotransferases have been observed; elevations in ALT or AST ≥3-times ULN were observed in up to 3.5% of FILSPARI‑treated patients in clinical studies ^[1].

Study Design

The indication was supported principally by DUPLEX, a global, multicenter, randomized, double‑blind, parallel‑group, active‑controlled phase 3 study that randomized 371 patients to sparsentan or irbesartan and treated patients for 108 weeks with planned assessment at Week 108; DUPLEX included adults and pediatric subjects aged 8 years and older with biopsy‑proven FSGS or a genetic mutation associated with FSGS and UPCR ≥1.5 g/g ^[6]^[4]^[5]. The sponsor and FDA referenced both an interim proteinuria‑based analysis and the final eGFR‑based analysis in regulatory review; the FDA’s approval for FSGS without nephrotic syndrome was supported by the proteinuria effect observed in the non‑nephrotic subgroup of DUPLEX ^[5]^[6]^[2].

FAQ

What is FILSPARI (sparsentan) approved for?

FILSPARI (sparsentan) is approved to reduce proteinuria in adult and pediatric patients aged 8 years and older with focal segmental glomerulosclerosis (FSGS) without nephrotic syndrome. The approval applies to patients meeting the labeled criteria and includes specific REMS, contraindications, and monitoring requirements described in the prescribing information.

How does sparsentan work?

Sparsentan is a single molecule that antagonizes the endothelin type A (ETA) receptor and the angiotensin II type 1 (AT1) receptor. Its dual ETA and AT1 receptor antagonism is the basis for its effect on proteinuria in glomerular disease such as FSGS, as described in the product labeling.

What is the recommended dose of FILSPARI?

For patients with FSGS aged 8 years and older and weighing greater than 50 kg, initiate FILSPARI at 400 mg orally once daily for 14 days then increase to 800 mg once daily as tolerated; for patients weighing 50 kg or less, initiate at 200 mg once daily for 14 days then increase to 400 mg once daily as tolerated. When resuming after interruption, consider re‑titration. Clinicians should consult current prescribing information for complete dosing guidance.

What are the most common side effects?

The most commonly reported adverse reactions in patients with FSGS (≥5%) include peripheral edema, hypotension (including orthostatic hypotension), hyperkalemia, dizziness, and anemia. FILSPARI carries a boxed warning for hepatotoxicity and embryo‑fetal toxicity; baseline aminotransferases and bilirubin are required and ALT/AST must be monitored every 3 months during treatment. Enrollment in the FILSPARI REMS is required prior to prescribing.

FDA Approves Sparsentan for FSGS Without Nephrotic Syndrome: 29% Proteinuria Reduction in DUPLEX Non‑Nephrotic Subgroup

Direct Clinical Takeaway & Evidence Summary

FDA Approves Sparsentan for FSGS Without Nephrotic Syndrome: 29% Proteinuria Reduction in DUPLEX Non‑Nephrotic Subgroup

Clinical Perspective

Clinical Context

Key Findings

Safety & Tolerability

Study Design

FAQ

References

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