Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
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 |
|---|---|---|---|---|
| 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 being studied for the treatment of ANCA Associated Vasculitis, Focal Segmental Glomerulosclerosis, and Immunoglobulin A Nephropathy. It is in Phase 2 and Phase 3 clinical trials for these kidney-related conditions.
Sparsentan is being developed by Travere Therapeutics, Inc., a biopharmaceutical company traded on the NASDAQ under the ticker symbol TVTX. The company is conducting multiple clinical trials to evaluate the drug's safety and efficacy in various glomerular diseases.
Sparsentan is in Phase 2 and Phase 3 clinical development. It has completed a Phase 3 trial in Focal Segmental Glomerulosclerosis, has an active Phase 3 trial in Immunoglobulin A Nephropathy, and is in Phase 2 trials for pediatric glomerular diseases and ANCA-associated vasculitis.
Sparsentan is being evaluated in several trials, including NCT03493685 (completed Phase 3 in FSGS), NCT03762850 (active Phase 3 in IgA Nephropathy), NCT05003986 (recruiting Phase 2 in pediatric glomerular diseases), and NCT05630612 (active Phase 2 in ANCA-associated vasculitis).
Sparsentan is not FDA approved. It is an investigational drug currently in clinical development. While a Phase 3 trial in Focal Segmental Glomerulosclerosis has been completed, regulatory approval has not been granted, and the drug remains under investigation for all its studied indications.
Sparsentan is a small molecule that acts as a dual antagonist of the endothelin A (ETA) receptor and the angiotensin II type 1 (AT1) receptor. By blocking these receptors, it aims to reduce proteinuria and slow the progression of kidney damage in glomerular diseases.