Sparsentan

Sparsentan is a single molecule with antagonism of the endothelin type A receptor (ET A R) and the angiotensin II type 1 receptor (AT 1 R). Sparsentan has high affinity for both the ET A R (Ki= 12.8 nM) and the AT 1 R (Ki=0.36 nM), and greater than 500-fold selectivity for these receptors over the endothelin type B and angiotensin II subtype 2 receptors.

• FILSPARI is an endothelin and angiotensin II receptor antagonist indicated: • To slow kidney function decline in adults with primary immunoglobulin A nephropathy (IgAN) who are at risk for disease progression ( 1.1 , 12.1 , 14.1 ). • To reduce proteinuria in adult and pediatric patients aged 8 years and older with focal segmental glomerulosclerosis (FSGS) without nephrotic syndrome ( 1.2 , 12.1 , 14.2 ).

• Use of FILSPARI is contraindicated in patients who are pregnant [see Dosage and Administration ( 2.3 ), Warnings and Precautions ( 5.3 ), Use in Specific Populations ( 8.1 )] . Do not co-administer FILSPARI with ARBs, ERAs, or aliskiren [see Dosage and Administration ( 2.1 ), Drug Interactions ( 7.1 )].contraindicated

• Prior to initiating treatment with FILSPARI, discontinue use of renin- angiotensin-aldosterone system (RAAS) inhibitors and endothelin receptor antagonists (ERAs) ( 2.1 , 4 , 7.1 ). • IgAN (Adult Patients): Initiate treatment with FILSPARI at 200 mg orally once daily. After 14 days, increase to 400 mg once daily, as tolerated. ( 2.4 ) • FSGS (Adult and Pediatric Patients 8 years and older): • Greater than 50 kg: Initiate treatment with FILSPARI at 400 mg orally once daily. After 14 days, increase to 800 mg once daily, as tolerated ( 2.4 ). • 50 kg and less: Initiate treatment with FILSPARI at 200 mg orally once daily. After 14 days, increase to 400mg once daily, as tolerated ( 2.4 ). • When resuming FILSPARI after interruption, consider re-titration ( 2.4 ). • Instruct patients to swallow tablets whole with water prior to the morning or evening meal ( 2.5 ). • For patients who are unable to swallow whole tablets, FILSPARI may be crushed and mixed with water immediately before administration ( 2.5 , 12.3 ). 2.1 General Considerations Prior to initiating treatment with FILSPARI, discontinue use of renin-angiotensin-aldosterone system (RAAS) inhibitors and endothelin receptor antagonists (ERAs) [see Contraindications ( 4 ), Drug Interactions ( 7.1 )] . 2.2 Monitoring Initiate treatment with FILSPARI only after measuring aminotransferase levels and total bilirubin. Avoid initiation in patients with elevated aminotransferases greater than 3 times ULN.

• Hypotension ( 5.4 ) • Acute Kidney Injury ( 5.5 ) • Hyperkalemia ( 5.6 ) • Fluid Retention ( 5.7 ) 5.1 Hepatotoxicity Elevations in ALT or AST of at least 3-fold ULN have been observed in up to 3.5% of FILSPARI-treated patients, including cases confirmed with rechallenge [see Adverse Reactions ( 6.1 )] . While no concurrent elevations in bilirubin greater than 2-times ULN or cases of liver failure were observed in FILSPARI-treated patients in clinical trials, some endothelin receptor antagonists have caused elevations of aminotransferases, hepatotoxicity, and liver failure. To reduce the risk of potential serious hepatotoxicity, measure serum aminotransferase levels and total bilirubin prior to initiation of treatment and then every 3 months during treatment [see Dosage and Administration ( 2.2 )] . Advise patients with symptoms suggesting hepatotoxicity (nausea, vomiting, right upper quadrant pain, fatigue, anorexia, jaundice, dark urine, fever, or itching) to immediately stop treatment with FILSPARI and seek medical attention. If aminotransferase levels are abnormal at any time during treatment, interrupt FILSPARI and monitor as recommended [see Dosage and Administration ( 2.6 )] . Consider re-initiation of FILSPARI only when hepatic enzyme levels and bilirubin return to pretreatment values and only in patients who have not experienced clinical symptoms of hepatotoxicity [see Dosage and Administration ( 2.2 , 2.6 )] .

Clinically significant adverse reactions that appear in other sections of the label include: • Hepatotoxicity [see Warnings and Precautions ( 5.1 )] • Embryo-Fetal Toxicity [see Warnings and Precautions ( 5.3 )] • Hypotension [see Warnings and Precautions ( 5.4 )] • Acute Kidney Injury [see Warnings and Precautions ( 5.5 )] • Hyperkalemia [see Warnings and Precautions ( 5.6 )] • Fluid Retention [see Warnings and Precautions ( 5.7 )] Most common adverse reactions in patients with IgAN (≥5%) are hyperkalemia, hypotension (including orthostatic hypotension), peripheral edema, dizziness, anemia, and acute kidney injury ( 6.1 ). Most common adverse reactions in patients with FSGS (≥5%) are peripheral edema, hypotension (including orthostatic hypotension), hyperkalemia, dizziness, and anemia ( 6.1 ). To report SUSPECTED ADVERSE REACTIONS, contact Travere Therapeutics at 1-877-659-5518 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. IgAN The safety of FILSPARI was evaluated in PROTECT ( NCT03762850 ), a randomized, double-blind, active-controlled clinical study in adults with IgAN. The data below reflect FILSPARI exposure in 202 patients with a median duration of 110 weeks. The most common adverse reactions are presented in Table 3 .

• Lactation: Advise not to breastfeed ( 8.2 ). 8.1 Pregnancy Risk Summary Based on data from animal reproductive toxicity studies, FILSPARI may cause fetal harm, including birth defects and fetal death, when administered to a pregnant patient and is contraindicated during pregnancy [see Contraindications ( 4 )] . Available data from reports of pregnancy in clinical trials with FILSPARI are insufficient to identify a drug-associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes. Available data from postmarketing reports and published literature over decades of use with ERA in the same class as FILSPARI have not identified an increased risk of fetal harm; however, these data are limited. Methodological limitations of these postmarketing reports and published literature include lack of a control group; limited information regarding dose, duration, and timing of drug exposure; and missing data. These limitations preclude establishing a reliable estimate of the risk of adverse fetal and neonatal outcomes with maternal ERA use.

Metabolism

The pharmacokinetics of sparsentan are presented as geometric mean (% coefficient of variation) unless otherwise specified. The C max and AUC of sparsentan increase less than proportionally following administration of single doses of 200 mg to 1600 mg.

There is no experience with overdose with FILSPARI. Sparsentan has been given in doses up to 1600 mg/day in healthy volunteers, or up to 800 mg/day in patients. Overdose of FILSPARI may result in decreased blood pressure. In the event of an overdose, standard supportive measures should be taken, as required. Dialysis is unlikely to be effective because sparsentan is highly protein-bound.

• Feb 17, 2023NDANDA216403Travere

1. 1Dizziness74614%
2. 2Fatigue67713%
3. 3Hypotension55711%
4. 4Nausea3506.8%
5. 5Product Use In Unapproved Indication3356.5%
6. 6Off Label Use3076.0%
7. 7Headache3035.9%
8. 8Peripheral Swelling2885.6%
9. 9Pruritus2565.0%
10. 10Product Administration Error2544.9%
11. 11Product Dose Omission Issue2204.3%
12. 12Glomerular Filtration Rate Decreased1923.7%
13. 13Blood Pressure Decreased1843.6%
14. 14Blood Creatinine Increased1813.5%
15. 15Drug Ineffective1743.4%

The 10 most recently updated of 11 ClinicalTrials.gov registrations naming Sparsentan as an intervention. Registration is not evidence of efficacy or safety — reference crosswalk only.

• A Study of the Safety and Activity of Sparsentan for the Treatment of Patients With Immunoglobulin A Nephropathy
  Recruiting · Phase 2 · Interventional · 24 enrolled · University of Leicester
  NCT04663204updated 2026-06-03
• Sparsentan for the Treatment of VEGF Signaling Pathway Inhibitor-Associated Proteinuria
  Not yet recruiting · Phase 1 · Interventional · 20 enrolled · Brigham and Women's Hospital
  NCT07224776updated 2026-05-18
• Study of Sparsentan Treatment in Pediatrics With Proteinuric Glomerular Diseases
  Recruiting · Phase 2 · Interventional · 67 enrolled · Travere Therapeutics, Inc.
  NCT05003986updated 2026-05-12
• Clinical Experience With Sparsentan in Switzerland in IgA Nephropathy
  Not yet recruiting · Observational · 50 enrolled · Waid City Hospital, Zurich
  NCT07555301updated 2026-04-29
• A Study of the Effect and Safety of Sparsentan in the Treatment of Patients With IgA Nephropathy
  Active not recruiting · Phase 3 · Interventional · 406 enrolled · Travere Therapeutics, Inc.
  NCT03762850updated 2026-04-20
• Study of Sparsentan in Patients With Primary Focal Segmental Glomerulosclerosis (FSGS)
  Completed · Phase 3 · Interventional · 371 enrolled · Travere Therapeutics, Inc.
  NCT03493685updated 2026-04-17
• Sparsentan in Posttransplant Immunoglobulin A Nephropathy or Focal Segmental Glomerulosclerosis
  Recruiting · Phase 4 · Interventional · 20 enrolled · Travere Therapeutics, Inc.
  NCT07219121updated 2026-02-27
• A Study to Investigate Safety and Effect of Sparsentan in Combination With SGLT2 Inhibition in Participants With IgAN
  Completed · Phase 2 · Interventional · 48 enrolled · Travere Therapeutics, Inc.
  NCT05856760updated 2025-11-20
• ETA and AT1 Antagonism in ANCA-vasculitis (SPARVASC)
  Active not recruiting · Phase 2 · Interventional · 32 enrolled · University of Edinburgh
  NCT05630612updated 2025-08-24
• Randomized, Double-Blind, Safety and Efficacy Study of RE-021 (Sparsentan) in Focal Segmental Glomerulosclerosis
  Completed · Phase 2 · Interventional · 109 enrolled · Travere Therapeutics, Inc.
  NCT01613118updated 2025-05-15

Frequently asked questions

How does Sparsentan work?

Sparsentan is a single molecule with antagonism of the endothelin type A receptor (ET A R) and the angiotensin II type 1 receptor (AT 1 R). Sparsentan has high affinity for both the ET A R (Ki= 12.8 nM) and the AT 1 R (Ki=0.36 nM), and greater than 500-fold selectivity for these receptors over the endothelin type B and angiotensin II subtype 2 receptors.

What is Sparsentan used for?

According to FDA labeling, Sparsentan carries indications including: FILSPARI is an endothelin and angiotensin II receptor antagonist indicated: • To slow kidney function decline in adults with primary immunoglobulin A nephropathy (IgAN) who are at risk for disease progression ( 1.1 , 12.1 , 14.1 ). • To reduce proteinuria in adult and pediatric patients aged 8 years and older with focal segmental glomerulosclerosis (FSGS) without nephrotic syndrome ( 1.2 , 12.1 , 14.2 ).. This is a reference summary of labeled uses, not medical advice or a treatment recommendation.

What class of drug is Sparsentan?

Sparsentan is classified as Other agents acting on the renin-angiotensin system, Angiotensin 2 Receptor Blocker, Endothelin Receptor Antagonist, Angiotensin 2 Type 1 Receptor Antagonists, Breast Cancer Resistance Protein Inhibitors, Cytochrome P450 2B6 Inducers, Cytochrome P450 2C19 Inducers, Cytochrome P450 2C9 Inducers, Endothelin Receptor Antagonists, P-Glycoprotein Inhibitors.

What are the brand names for Sparsentan?

Sparsentan is marketed under brand names including Filspari.

What are the contraindications for Sparsentan?

Sparsentan labeling lists contraindications including: Use of FILSPARI is contraindicated in patients who are pregnant [see Dosage and Administration ( 2.3 ), Warnings and Precautions ( 5.3 ), Use in Specific Populations ( 8.1 )] . Do not co-administer FILSPARI with ARBs, ERAs, or aliskiren [see Dosage and Administration ( 2.1 ), Drug Interactions ( 7.1 )].. Always consult the full prescribing information and a clinician.