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The FDA for proteinuria in IgA nephropathy, Travere Therapeutics announced, marking the first non-immunosuppressive therapy for this rare condition.

Also known as Berger's disease, proteinuria in IgA nephropathy is the leading cause of kidney failure due to glomerular disease, and sparsentan is specifically indicated to reduce proteinuria in adults at risk of rapid disease progression -- typically those with a urine protein-to-creatinine ratio of 1.5 g/g or higher.

The once-daily oral drug works by selectively targeting two critical pathways in the disease progression of IgA nephropathy -- endothelin-1 and angiotensin II.

Underpinning the approval is the , which compared 400 mg of sparsentan with 300 mg of irbesartan in 404 adult patients with IgA nephropathy and persistent proteinuria even with angiotensin-converting enzyme (ACE) therapy or angiotensin-receptor blockers (ARBs). Patients on sparsentan from baseline versus a drop of 15% in irbesartan-treated patients after 36 weeks, meeting the trial's primary endpoint (P<0.0001).

"Today's approval of Filspari sets the stage for a new standard of care for IgA nephropathy patients," Brad Rovin, MD, of the Ohio State University Wexner Medical Center in Columbus and a member of the PROTECT clinical trial steering committee, said in a statement from the drugmaker.

"A high proportion of individuals diagnosed with this disease do not sufficiently respond to the historical standard treatment, which has been therapies that are not indicated for IgA nephropathy," added Rovin. "As a result, many patients have struggled to manage their disease and have progressed more quickly to kidney failure."

It has not yet been established if sparsentan can slow kidney function decline in patients with this condition, but the ongoing 110-week trial will measure the drug's effect on estimated glomerular filtration rate slope in a confirmatory endpoint analysis, with results expected later this year. Travere said that continued approval of sparsentan may be contingent upon these results.

The most common adverse events observed in clinical studies of sparsentan included peripheral edema, hypotension (including orthostatic hypotension), dizziness, hyperkalemia, and anemia.

The label carries a boxed warning regarding risk for embryo-fetal toxicity and hepatotoxicity, and notes that the product shouldn't be used in patients with elevated aminotransferases (i.e., over three times the upper limit of normal). Sparsentan is also contraindicated for use with ARBs, endothelin receptor antagonists, and the renin inhibitor aliskiren.

Transaminases and bilirubin should be measured prior to starting treatment, and then monthly during the first year on treatment with sparsentan, as well as every 3 months thereafter.

Travere said the treatment will be available beginning the week of February 27, under a risk evaluation and mitigation strategy (REMS) that outlines specific requirements for prescriber, patients, and pharmacies.

Sparsentan is also currently being studied in the ongoing phase III for focal segmental glomerulosclerosis following positive phase II DUET trial findings released in 2018.

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