What are the efficacy, functions and side effects of sparsentan?

Sparsentan can reduce proteinuria and is suitable for reducing proteinuria in adult patients with primary immunoglobulin A nephropathy who are at risk of rapid disease progression. The most common side effects include peripheral edema, hypotension, dizziness, hyperkalemia, and anemia.

spasintan

Developed by Travere Therapeutics, it was approved by the US FDA on February 17, 2023, for the reduction of proteinuria in adults with primary IgA (immunoglobulin A) nephropathy who are at risk for rapid disease progression (usually with a urine protein to creatinine ratio (UP/C) greater than or equal to 1.5).

Efficacy and effects of sparsentan

1. Protect glomerular podocytes: Sparsentan can block the endothelin A receptor (ETA) and angiotensin II type 1 receptor (AT1) pathways and play a role in protecting glomerular podocytes.

2. Reduce proteinuria: Sparsentane can help patients reduce proteinuria and delay the progression of kidney disease. Able to control urinary protein. Delay the progression of kidney function.

3. Lower blood pressure and reduce kidney damage: Sparsentan has a dual blocking effect, which can block the angiotensin pathway and endothelin pathway, thereby lowering blood pressure and reducing kidney damage, which is beneficial for the treatment of kidney disease.

Sparsentan side effects

The more common side effects of sparsentan mainly include peripheral edema, hypotension, dizziness, hyperkalemia, anemia, acute kidney injury, and elevated transaminases. The more serious side effects mainly include hepatotoxicity, hypotension, acute kidney injury, hyperkalemia, and fluid retention.

How to deal with common side effects of Sparsentan

1. Peripheral edema: Depending on the severity of edema, consider adjusting the dose of sparsentane or temporarily discontinuing the drug. At the same time, reducing sodium intake can help control edema. Diuretics can also be used under the guidance of a doctor to reduce edema symptoms.

2. Hypotension: Consider adjusting the dose of sparsentan. Mild hypotension does not require special treatment. Severe hypotension needs to be treated with vasopressor drugs according to the doctor's advice.

3. Dizziness: Maintain adequate sleep time. When dizziness occurs, sit or lie down immediately to avoid falling.

4. Hyperkalemia: Limit the intake of high-potassium foods, such as bananas, oranges, tomatoes, etc., and use drugs such as potassium ion exchangers or diuretics under the guidance of a doctor to lower blood potassium levels.

5. Anemia: Iron supplements should be supplemented under the guidance of a doctor to increase red blood cell production.

6. Acute kidney injury: Suspend the use of sparsentane according to the doctor's advice, and limit water and sodium intake to avoid increasing the burden on the kidneys.

7. Elevated transaminase: Suspend the use of sparsentan under the guidance of a doctor, and at the same time give hepatoprotective and enzyme-lowering drugs, adjust your diet, and avoid drinking alcohol and high-fat foods.

How to deal with serious side effects of sparsentan

1. Hepatotoxicity: If symptoms of hepatotoxicity occur during medication, such as nausea, vomiting, right upper quadrant pain, jaundice, fever or itching, etc., immediately stop treatment with sparsentan and seek medical treatment in time.

2. Hypotension: Consider eliminating or adjusting other antihypertensive drugs and maintaining appropriate volume status. If hypotension still occurs after stopping or reducing other antihypertensive drugs, consider reducing the dose of spaxentan or interrupting the administration.

3. Acute kidney injury: If clinically significant renal function decline occurs during medication, suspension or discontinuation of treatment should be considered.

4. Hyperkalemia: Monitor serum potassium regularly and provide appropriate treatment.

5. Fluid retention: Determine the cause and whether it is necessary to start or adjust the dose of diuretic treatment in a timely manner, and then consider adjusting the dose of sparsentan.

Clinical studies of sparsentin

In an international, randomized, double-blind, active-controlled study, 404 adult patients with IgA nephropathy and proteinuria of 10 g/day or more compared the efficacy of sparsentan and irbesartan. Patients were randomly assigned to receive sparsentan (n=202) or irbesartan (n=202).

The geometric least squares mean percent change from baseline in the urine protein/creatinine ratio at Week 36 was statistically significant in the sparsentan group (49.8%) compared with the irbesartan group (15.1%), resulting in a relative reduction of 41% between groups.

Once-daily treatment with sparsentan resulted in meaningful reductions in proteinuria compared with irbesartan in adults with IgA nephropathy.

Summary

Sparsentan reduces proteinuria in patients with IgAN and FSGS and expedites FDA approval of IgAN in patients at risk for rapid disease progression (usually urine protein/creatinine ratio (UPCR) ≥1.5 g/g). Interim results from PROTECT and DUET show promise for improving proteinuria in patients with IgAN and FSGS.

References:

Heerspink HJL, Radhakrishnan J, Alpers CE, Barratt J, Bieler S, Diva U, Inrig J, Komers R, Mercer A, Noronha IL, Rheault MN, Rote W, Rovin B, Trachtman H, Trimarchi H, Wong MG, Perkovic V; PROTECT Investigators. Sparsentan in patients with IgA nephropathy: a prespecified interim analysis from a randomized, double-blind, active-controlled clinical trial. Lancet. 2023 May 13;401(10388):1584-1594. doi: 10.1016/S0140-6736(23)00569-X. Epub 2023 Apr 1. PMID: 37015244.

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