Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Label indication 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 ). FDA label
Also known as Filspari, RE-021, RE-021 (Sparsentan)
Sparsentan · 6 trials · 12 indications
24-hour urine sample was collected for analysis of UP/C via a mixed-model repeated-measures (MMRM) analysis. Missing responses were imputed prior to analysis using multiple imputation. Change from Baseline during the double-blind period in UP/C on the log scale was the dependent variable. Log Baseline UP/C was included as a covariate along with fixed effects for randomized treatment, time (ie, nominal visit in weeks), randomized treatment-by-time interaction, and randomization strata with participants as random effect. Estimates in log scale were back transformed. Baseline was defined as the last non-missing observation on or prior to the start of the dosing. Using Rubin's approach, estimated treatment effects are combined across all imputations to obtain overall estimates.
The total eGFR slope over 2 years, defined as the slope of eGFR following initiation of randomized treatment (ie, Day 1 to Week 108). Estimates are calculated from a mixed-effects model with treatment, Baseline eGFR, analysis visit, treatment-by-analysis visit, randomization stratification factors as fixed effects, and intercept and slope for each participant as a random effect.
Percentage of participants achieving FPRE, defined as urine protein-to-creatinine ratio (UP/C) ≤1.5 grams/gram (g/g) (170 milligrams per millimoles \[mg/mmol\]) and a \>40% reduction from Baseline was analyzed using a generalized linear model to model probability of achieving FPRE. Missing responses were imputed prior to analysis using multiple imputation. A generalized linear model with appropriate link function was implemented with Baseline log (UP/C), treatment, analysis visit, treatment by analysis visit interaction, and randomization strata as fixed effects. For estimates of probability of achieving FPRE, risk difference, and odds ratio, binomial distribution with logit link was used. For relative risk, Poisson distribution with log link was used. Using Rubin's approach, estimated treatment effects are combined across all imputations to obtain overall estimates for probabilities.
The change from baseline in UA/C at Week 24 based on first morning void (FMV) samples
Change from baseline to week 6 in acetylcholine-mediated forearm blood flow vasodilatation
The incidence of TEAEs, SAEs, AEs leading to treatment discontinuation, and AEOIs
Change from baseline in UP/C over 108 weeks
The primary efficacy endpoint is the change from baseline in the urine protein/creatinine ratio (UP/C), based on a 24-hour urine sample, at Week 36.
| Arm | Type | Description |
|---|---|---|
| sparsentan | EXPERIMENTAL | Double-blind: Sparsentan will be administered daily as a 200-mg oral tablet, over-encapsulated (blinded) size 00 capsule for the first 2 weeks of the study following randomization. For patients who tolerate the initial dose of 200 mg after 2 weeks will increase their dose to 400- mg and continue treatment to Week 110. |
| irbesartan | ACTIVE_COMPARATOR | Double-blind: Irbesartan will be administered daily as a 150-mg oral tablet, over-encapsulated (blinded) size 00 capsule for the first 2 weeks of the study following randomization. For patients who tolerate the initial dose of 150 mg after 2 weeks will increase their dose to 300 mg and continue treatment to Week 110. |
| dapagliflozin + sparsentan (Sub study) | EXPERIMENTAL | OLE Sub study: Dapagliflozin will be administered daily as a 5-mg oral tablet, in addition to 400-mg of Sparsentan, for a period of 12 weeks. |
| sparsentan (Sub Study) | EXPERIMENTAL | OLE Sub study: Sparsentan will be administered daily as a dose of 400-mg for a period of 12 weeks. |
| sparsentan for double-blind and open-label extension | EXPERIMENTAL | Sparsentan will be administered as a single oral dose; an initial dose of 400 mg daily titrating up to a target dose of 800 mg, daily |
| Population 1: FSGS and/or MCD | EXPERIMENTAL | Subjects with selected proteinuric glomerular diseases associated with FSGS and MCD histological patterns |
| Population 2: IgAN, IgAV, or AS | EXPERIMENTAL | Subjects with kidney biopsy-confirmed immunoglobulin A nephropathy (IgAN), immunoglobulin A vasculitis (IgAV), or Alport syndrome (AS) |
| Population 3: IgAN | EXPERIMENTAL | Subjects with kidney biopsy-confirmed IgAN |
| Name | Type | Description |
|---|---|---|
| sparsentan | DRUG | Target dose of 400 mg daily |
| irbesartan | DRUG | Target dose of 300 mg daily |
| Dapagliflozin | DRUG | Target dose of 10 mg daily |
Key Inclusion Criteria for the Double-Blind Period: * Age 18 years or older at screening * Biopsy-proven primary IgAN * Proteinuria of ≥1 g/day at screening * eGFR ≥30 mL/min/1.73 m2 at screening * Currently on stable dose of ACEI and/or ARB therapy, for at least 12 weeks prior to screening (maximu...
| Company | Ticker | Trials | Lead Phase | Drugs |
|---|---|---|---|---|
| Apellis Pharmaceuticals, Inc. | APLS | 1 | PHASE2 | APL-2 |
| Sanofi SA Sponsored ADR | SNY | 1 | PHASE2 | Frexalimab, Brivekimig, rilzabrutinib |
| Novartis AG Sponsored ADR | NVS | 1 | PHASE2 | Atrasentan |
| Akebia Therapeutics, Inc. | AKBA | 1 | PHASE2 | Praliciguat |
| Travere Therapeutics, Inc. | TVTX | 1 | PHASE2 | Sparsentan |
| Vera Therapeutics, Inc. Class A | VERA | 1 | PHASE2 | Atacicept |
Sparsentan is an investigational small molecule developed by Travere Therapeutics, Inc. (TVTX) for immunology indications including Immunoglobulin A Nephropathy, Focal Segmental Glomerulosclerosis, and ANCA Associated Vasculitis. It is being studied in Phase 2 clinical trials and has not been approved by the FDA.
Sparsentan targets EDNRA and AGTR1 as a dual antagonist. By blocking both the endothelin A receptor and the angiotensin II type 1 receptor, it acts on two pathways involved in proteinuric glomerular diseases, which is the basis for its study in Immunoglobulin A Nephropathy, Focal Segmental Glomerulosclerosis, and ANCA Associated Vasculitis.
Sparsentan is developed by Travere Therapeutics, Inc., which trades under the ticker TVTX. The company is running the clinical development program for the drug across its immunology indications.
Sparsentan is in Phase 2 clinical development. It is investigational and has not been approved by the FDA. Its Phase 2 program includes completed and ongoing studies, with one trial listed as active and not recruiting, and others recruiting or completed.
Sparsentan has been studied in several Phase 2 trials. These include NCT05856760 in Immunoglobulin A Nephropathy, NCT05630612 in ANCA Associated Vasculitis, NCT05003986 in pediatric proteinuric glomerular diseases, and NCT04663204 in Immunoglobulin A Nephropathy. The trials span the United States, United Kingdom, Hong Kong, and multiple European countries.
Sparsentan is being studied as a treatment for Immunoglobulin A Nephropathy in Phase 2 clinical trials, including NCT05856760 and NCT04663204. It is an investigational therapy and is not approved for this or any other indication.