What Is Sparsentan?
Sparsentan is a medication under investigation for the treatment of various kidney diseases. It is an endothelin-1 antagonist, meaning it works by blocking specific receptors that contribute to kidney damage and inflammation. By targeting these pathways, sparsentan aims to reduce protein in the urine (proteinuria) and help protect overall kidney function. The drug is primarily being studied for conditions such as Focal Segmental Glomerulosclerosis (FSGS) and Immunoglobulin A Nephropathy (IgAN). Across 11 clinical trials, sparsentan has been studied in a total of 1,182 participants, with the first trial starting in 2012 and the latest projected to conclude in 2026. These studies are sponsored by organizations including Travere Therapeutics, Inc., Brigham and Women's Hospital, and the University of Edinburgh.Uses and Conditions Under Study
Sparsentan is being investigated for its potential to treat several kidney-related conditions, with a strong focus on those characterized by proteinuria and progressive kidney damage.- Immunoglobulin A Nephropathy (IgAN): This is a kidney disease where immune complexes build up in the kidneys, leading to inflammation and damage. Sparsentan is being studied in 4 trials for IgAN, including patients who have received a kidney transplant. Researchers are observing its effects on markers like albuminuria and glomerular filtration rate (GFR), as well as the mean percent change in urine protein to creatinine ratio, with the goal of reducing protein in the urine and slowing disease progression.
- Focal Segmental Glomerulosclerosis (FSGS): FSGS is a rare kidney disease that causes scarring in the filtering units of the kidneys (glomeruli), leading to significant protein loss in the urine. Sparsentan is being evaluated in 4 trials for FSGS, with studies aiming to assess its safety, feasibility, and ability to reduce proteinuria.
- Proteinuria and General Kidney Diseases: Sparsentan is also being investigated more broadly for proteinuria (excess protein in the urine) in 2 trials, and for general kidney diseases in 2 trials. These studies often include conditions like glomerulonephritis and IgA vasculitis, which can also lead to kidney damage and protein loss.
- Healthy Subjects: One trial involving healthy subjects is being conducted to understand how sparsentan is processed by the body and to assess its safety profile.
Dosing
Sparsentan has been studied in various oral forms, including an oral suspension. Clinical trials have investigated different strengths and administration schedules to determine the most effective and safest dosing regimen. Doses of 200 mg, 400 mg, and 800 mg have been investigated in participants. Typically, participants in studies begin with a dose of 200 mg once daily (QD), often taken prior to the morning meal. This dose may then be increased, or 'titrated,' to a target of 400 mg once daily, based on tolerability and safety as determined by the investigator. Some studies have also explored higher doses, such as 800 mg, for specific populations. The administration of sparsentan has been studied in both fasted and fed states to understand how food might affect its absorption. In some trials, sparsentan treatment has been compared to irbesartan 300 mg, another medication used for kidney conditions, to evaluate its efficacy.Side Effects
Information regarding the specific side effects of Sparsentan from clinical trials was not provided in the source data. Therefore, a detailed list of common side effects, their frequencies, and comparisons to placebo cannot be presented at this time.
Clinical Trial Results
Clinical trials have evaluated Sparsentan for its effects on kidney diseases, specifically Focal Segmental Glomerulosclerosis (FSGS) and IgA Nephropathy (IgAN).
Focal Segmental Glomerulosclerosis (FSGS)
In a study (NCT01613118) comparing Sparsentan to irbesartan in patients with FSGS, Sparsentan demonstrated a greater reduction in urine protein levels. Patients receiving any dose of Sparsentan (200, 400, or 800 mg pooled) experienced a 44.8% reduction in urine protein/creatinine ratio, compared to an 18.5% reduction for those on irbesartan 300 mg. Specifically, patients on Sparsentan 400 mg saw the largest reduction, with a 52.7% decrease. Achieving a partial remission endpoint (FPRE) was also more common with Sparsentan; 28.13% of patients on pooled Sparsentan doses achieved FPRE, versus 9.38% on irbesartan. The 400 mg dose of Sparsentan showed the highest rate of FPRE, with 38.10% of patients reaching this goal.
Another study (NCT03493685) in patients with primary FSGS also showed improved outcomes with Sparsentan. A higher percentage of participants achieved the FSGS Partial Remission Endpoint (FPRE) with Sparsentan (42.0%) compared to irbesartan (26.0%). The rate of decline in estimated glomerular filtration rate (eGFR) was slower for patients on Sparsentan, with an eGFR slope of -4.8 milliliters/minute/1.73 square meter/year following the initial acute effect, compared to -5.7 milliliters/minute/1.73 square meter/year for irbesartan, indicating better preservation of kidney function over time.
IgA Nephropathy (IgAN)
In a study (NCT03762850) evaluating Sparsentan in patients with IgA Nephropathy, Sparsentan significantly reduced protein in the urine. Patients treated with Sparsentan experienced a 49.77% reduction in urine protein/creatinine ratio at week 36, while those on irbesartan saw a 15.05% reduction. Sparsentan also showed a slower decline in kidney function, with an annualized eGFR slope of -2.7 milliliters/minute/1.73 square meter/year, compared to -3.8 milliliters/minute/1.73 square meter/year for irbesartan, suggesting a better long-term preservation of kidney function.
A study (NCT05856760) investigating Sparsentan in combination with SGLT2 inhibition in IgAN patients showed further positive results. At week 24, patients experienced a 55.78% reduction in urine albumin-creatinine ratio (UA/C).
- 77% of participants achieved a 30% reduction from baseline in UA/C.
- 51% of participants achieved a 50% reduction from baseline in UA/C.
- 31% of participants achieved a low UA/C of less than 0.2 g/g.
Additionally, Sparsentan treatment resulted in reductions in blood pressure, with a decrease of 3.4 mmHg in systolic blood pressure and 4.6 mmHg in diastolic blood pressure at week 24.
Currently Recruiting Trials
Sparsentan is currently being investigated in clinical trials to understand its potential benefits for patients with specific kidney conditions. These studies aim to gather more information about how safe and effective sparsentan is in different patient populations.
One ongoing study, NCT07219121, is a Phase 4 trial evaluating sparsentan in patients who have undergone a kidney transplant. This study focuses on individuals experiencing proteinuria, a sign of kidney damage, due to Immunoglobulin A (IgA) Nephropathy or Focal Segmental Glomerulosclerosis after their transplant. Researchers are assessing the safety and efficacy of once-daily sparsentan tablets over a period of 36 weeks. The trial aims to enroll approximately 20 participants.
Another important study, NCT05003986, is a Phase 2 trial specifically designed for pediatric patients. This study is investigating sparsentan treatment in children and adolescents with various proteinuric glomerular diseases. Conditions being studied include Focal Segmental Glomerulosclerosis, Minimal Change Disease, Immunoglobulin A Nephropathy, IgA Vasculitis, and Alport Syndrome. The trial is evaluating the safety, efficacy, and tolerability of sparsentan oral suspension and tablets, with changes in proteinuria being assessed over 108 weeks of once-daily dosing. This study plans to enroll about 67 children and adolescents.
Where to Participate
Clinical trials for sparsentan are currently recruiting across a wide geographic area, with study sites located in 18 states, 26 cities, and a total of 32 sites. This broad reach helps ensure diverse participation in the research.
Top locations with multiple sites include:
- New York, New York
- Columbus, Ohio
- Miami, Florida
- Houston, Texas
- Seattle, Washington
- Philadelphia, Pennsylvania
Other participating cities include Minneapolis, Minnesota; Kansas City, Missouri; Hackensack, New Jersey; and Neptune City, New Jersey. The pediatric study, NCT05003986, is open to children aged 1 to 18 years, of all genders, who have specific proteinuric glomerular diseases. Healthy volunteers are not eligible for these studies.
Development Timeline
The journey of sparsentan in clinical development began on June 6, 2012, with the initiation of its first clinical trial. Since then, the drug has progressed through various stages of research, with the latest trial projected to conclude on April 29, 2026. Travere Therapeutics, Inc. has been a primary driver of this development, sponsoring 7 out of 11 trials. Other institutions, including Brigham and Women's Hospital and the University of Edinburgh, have also contributed to the research.
Initially, sparsentan was explored for conditions such as Irritable Bowel Syndrome with Constipation (IBS-C) and hyperphosphatemia. However, the development pipeline significantly expanded to focus on kidney-related conditions. The majority of studies have been in Phase 2, with 5 trials, alongside 2 Phase 1 and 2 Phase 3 trials, and 1 Phase 4 study. Across all trials, sparsentan has involved a total of 1,182 participants. The research has broadened to investigate a wide range of kidney diseases, including various forms of proteinuria, IgA Nephropathy, Focal Segmental Glomerulosclerosis, Minimal Change Disease, IgA Vasculitis, and Alport Syndrome, reflecting a strategic shift towards addressing unmet needs in renal care.