in pictures and a few words
What it is and why it matters
Sparsentan is a tablet for adults with one of the diseases of the kidney filters who are at high risk that their kidneys will weaken quickly. In this disease, one of the blood’s protective proteins settles in the filters.
- One tablet blocks at once two paths by which the kidney filter gets damaged
- It is the first medicine with this double action approved for this disease
What goes wrong in this disease
A protective blood protein is made with a flaw. The body takes it for a stranger and builds a defence against it.
- The clumps that form settle in the tiny filters of the kidney
- The filter becomes inflamed, and protein that should stay in the blood leaks into the urine
The cell that holds protein back
The main cell of the filter wraps around a vessel with its branches. Between them are gaps of exactly the right size.
- When the cell is damaged, the gaps widen
- The filter stops holding protein back, and it leaks into the urine
Two paths of damage — one tablet
The usual kidney-protecting medicines block one path of damage to the filter. There is a second one too — a substance that strongly narrows blood vessels, increases inflammation and damages filter cells.
- Sparsentan blocks both paths with one molecule
Less protein in the urine
Sparsentan was compared not with a dummy pill but with a usual kidney medicine. After about two years there was noticeably less protein in the urine on sparsentan.
- Protein in the urine is a handy sign: it responds quickly to treatment
Tested in people. Tested in people: a large study in adults with this kidney disease.
The kidneys weaken more slowly
The main goal of treatment is to preserve kidney function. In the same study it declined more slowly than on the usual medicine.
- That is why the medicine was approved for this disease
Tested in people. Tested in people: in the same large study in adults with this kidney disease.
How it is taken
These are tablets. They are started after a biopsy — a test of a small piece of kidney — and a check of how the kidneys work. The decision is made by a kidney doctor.
- A usual kidney medicine of the same kind is not added — it is replaced
- It is also not combined with other medicines that act on the same paths
- Watching blood pressure, eating less salt and not smoking are still needed
Important. Together with a usual medicine of the same kind, the risk is higher of a drop in blood pressure, too much potassium in the blood and worse kidney function.
Liver and pregnancy — under watch
The medicine can harm the liver. So liver tests are done before starting and regularly during treatment.
- The medicine is dangerous for an unborn baby
- Pregnancy is ruled out before starting and reliably prevented throughout treatment
- Blood pressure and blood potassium are also checked regularly
Important. In the US the medicine is supplied only through a special programme: an ordinary prescription is not enough, the doctor and the pharmacy must be enrolled in it.
Who should see a doctor first
Only a kidney doctor chooses this medicine — do not start it on your own.
- With liver disease the decision is individual, and tests are monitored
- It is not prescribed for another disease of the kidney filters — called FSGS
- Not suitable for those not ready to stop their usual kidney medicine
Important. The medicine is not suitable for pregnant women or those planning a pregnancy.
In one sentence
One tablet blocks two paths of damage to the kidney filter: in this disease there is less protein in the urine, and kidney function declines more slowly.
- A kidney doctor chooses the treatment and watches the liver
Key Points
Sparsentan (Filspari) is a tablet that blocks two targets with one molecule: the endothelin A receptor and the angiotensin II type 1 receptor. It is the first dual-blockade agent to gain an indication in IgA nephropathy — the most common glomerular disease in the world.
| Where | How it helps | What human studies showed |
|---|---|---|
| Primary IgA nephropathy in adults at high risk of progression | less protein in the urine than on an ARB | PROTECT (Lancet, 2023), 404 patients: at week 110 urine protein 40% lower than on irbesartan (−42.8% versus −4.4%) [1] |
| Kidney function in IgA nephropathy | kidney function is lost more slowly | in the same trial the rate of eGFR decline was −2.7 versus −3.8 mL/min/1.73 m² per year (difference 1.1; p=0.037) [1] |
How It Helps
What Breaks in IgA Nephropathy
Immunoglobulin A normally guards the mucous membranes. In this disease it is produced with a structural defect: part of the molecule lacks the sugars it should carry. The body reads such immunoglobulin as foreign and raises antibodies against it.
The resulting complexes settle in the glomeruli — the microscopic filters through which blood passes. Chronic inflammation begins, the filter is damaged, and protein that should stay in the blood escapes into the urine.
The key cell of that filter is the podocyte. It wraps around the capillary with foot processes, leaving slits of a strictly defined width between them. Damage to the podocyte means the slits widen and the barrier stops holding protein back. A full account of how the filter is built is in the separate guide on the podocyte.
Two Targets in One Molecule
For decades kidney protection has been built on suppressing the angiotensin system — the job of ACE inhibitors and ARBs. This lowers pressure inside the glomerulus and reduces protein loss.
But there is a second route of damage: endothelin, the most powerful vasoconstrictor peptide known. In glomerular disease it amplifies inflammation and damages podocytes directly.
Sparsentan closes both routes with one molecule: one part binds the angiotensin receptor, the other the endothelin A receptor.
| ARB (e.g. irbesartan) | Sparsentan | |
|---|---|---|
| Angiotensin II receptor | Blocked | Blocked |
| Endothelin A receptor | No | Blocked |
| Number of drugs | One pathway, one drug | Two pathways, one drug |
| Restricted programme in the US | No | Yes (REMS) |
What the Trials Showed
Sparsentan was tested in two large trials — in IgA nephropathy (PROTECT [1]) and in focal segmental glomerulosclerosis (FSGS; DUPLEX [2]). In both the comparator was irbesartan, an ordinary ARB rather than placebo: an honest bar.
Protein in the urine is a marker. It is convenient: quick to measure, responsive to treatment within weeks rather than years. The goal is something else — preserving kidney function and postponing dialysis — and that takes years of follow-up to show.
In IgA nephropathy sparsentan delivered both results: urine protein fell and kidney function began to be lost more slowly. That is why the regulator first granted accelerated approval on proteinuria and full approval eighteen months later, once the two-year eGFR data arrived.
How to Take It
| Parameter | Detail |
|---|---|
| Formulation | Tablets |
| Who | Adults with primary IgA nephropathy at high risk of progression |
| Starting therapy | After biopsy and assessment of kidney function, by nephrologist decision |
| Monitoring | Liver enzymes, potassium, blood pressure, kidney function |
| Compatibility | Not combined with ACE inhibitors, ARBs or other endothelin antagonists |
Sparsentan does not replace the rest of treatment: blood pressure control, salt restriction and stopping smoking remain part of kidney care.
Who Should See a Doctor First
The decision belongs to a nephrologist: biopsy, assessment of kidney function, blood pressure control and baseline liver status are all required. Self-selection is out of the question here.
Precautions
▸Liver. The drug can cause hepatic injury. Enzymes are checked before starting and regularly during treatment. ▸Pregnancy. Acting on both the angiotensin system and endothelin is toxic to the fetus. Pregnancy is excluded before the start and reliably prevented during therapy. ▸Restricted programme. Because of these two risks the drug is distributed in the US through REMS: an ordinary prescription is not enough — prescriber and pharmacy must both be enrolled. ▸Blood pressure and potassium. Dual blockade affects blood pressure more than a single ARB; potassium is monitored.
Who It Is Not For
▸Anyone pregnant or planning pregnancy. ▸Patients with pre-existing liver disease — decided case by case and requiring monitoring. ▸Anyone already on an ACE inhibitor or ARB who is not prepared to stop it: these drugs are substituted, not stacked. ▸Patients with FSGS, under the current indication.
Bottom Line
▸Dual blockade of endothelin and angiotensin in one molecule is a new way of protecting the kidney filter. ▸PROTECT: urine protein 40% lower than on irbesartan, and kidney function lost more slowly — which is why the indication in IgA nephropathy was granted. ▸Treatment under a nephrologist: liver monitoring, excluded pregnancy, a REMS programme in the US.
Treatment can be discussed at a consultation; the drug can be ordered here.
References
1. Rovin BH, et al. Efficacy and safety of sparsentan versus irbesartan in patients with IgA nephropathy (PROTECT): 2-year results from a randomised, active-controlled, phase 3 trial. Lancet. 2023;402(10417):2077–2090. PMID 37931634
2. Rheault MN, et al. Sparsentan versus Irbesartan in Focal Segmental Glomerulosclerosis. N Engl J Med. 2023;389(26):2436–2445. PMID 37921461
3. Heerspink HJL, et al. Sparsentan in patients with IgA nephropathy: a prespecified interim analysis from a randomised, double-blind, active-controlled clinical trial. Lancet. 2023;401(10388):1584–1594. PMID 37015244
4. FILSPARI (sparsentan) — US Prescribing Information, Travere Therapeutics.
Caveats
What cannot be claimed yet:
▸That the drug works in FSGS. In DUPLEX (371 patients) partial remission of proteinuria at week 36 occurred in 42.0% versus 26.0% on irbesartan (p=0.009), and the effect held to week 108, but there was no difference in eGFR slope at week 108 [2], so there is no indication in FSGS. That is unproven benefit, not proven uselessness: FSGS gathers together conditions of differing cause, genetic forms included, and an effect is harder to demonstrate in so heterogeneous a group. ▸That a fall in protein automatically means preserved function. Urine protein is a surrogate marker, not the goal itself: in two diseases the same drug produced the same fall in protein and a different outcome for function, and the link has to be proven separately in each disease. ▸That it prevents kidney failure: in PROTECT the composite kidney failure endpoint was reached by 9% versus 13% — numerically favouring sparsentan, but not statistically significant [1]. ▸That it beats an ARB combined with something else — the comparator was irbesartan monotherapy, not a modern combination regimen. ▸Data beyond roughly two years are still limited.
This material is for information only and does not replace a consultation with a doctor.
Key facts
- Sparsentan (brand name Filspari, Travere Therapeutics) is a tablet that blocks the endothelin A receptor and the angiotensin II type 1 receptor at once: two targets in one molecule.
- PROTECT (Lancet, 2023): 404 patients with IgA nephropathy; at week 110 urine protein was 40% lower than on irbesartan (−42.8% versus −4.4%).
- In the same trial the rate of eGFR decline was −2.7 versus −3.8 mL/min/1.73 m² per year (difference 1.1; p=0.037) — kidney function was being lost more slowly.
- The FDA granted accelerated approval in February 2023 on the basis of proteinuria reduction, and full approval in September 2024, once an effect on the rate of kidney function loss was confirmed. The indication is primary IgA nephropathy in adults at risk of rapid progression. There is no indication for focal segmental glomerulosclerosis (FSGS).
- In the US the drug is dispensed under a restricted REMS programme because of hepatotoxicity and embryo-fetal toxicity: liver enzyme monitoring is mandatory and pregnancy must be excluded. It is not combined with ACE inhibitors, ARBs or other endothelin antagonists — it already occupies both of those positions.
