Filspari (Sparsentan) Rare Kidney Disease Drug Gets FDA Approval

Travere Therapeutics recently announced that their medication Filspari (sparsentan) received accelerated approval from the US Food and Drug Administration (FDA). The approval was granted for its use as a non-immunosuppressive therapy for the reduction of proteinuria (protein in urine) in IgA nephropathy in adults.

Filspari is the first single molecule dual endothelin angiotensin receptor antagonist (DEARA) approved for this indication. Patients must meet the criteria of a urine protein-to-creatinine ratio of ≥ 1.5 g/g and be at risk of rapid disease progression.

IgA nephropathy, also known as Berger’s disease, is a rare kidney disease that occurs due to build-up of the antibody immunoglobulin A in the kidneys. The build-up results in inflammation that impedes the kidney’s ability to filter the blood properly. The disease develops between the ages of 20 to 30 and progresses over time, often leading to end-stage kidney failure due to glomerular disease.

Presently, no cure exists for IgA nephropathy and approximately 150,000 people in the US alone are affected. About 30,000 to 50,000 of those affected can receive Filspari based on the indication that received accelerated approval.

The indication granted under the accelerated approval is based on the reduction of proteinuria in patients. It is not yet known whether Filspari slows decline in kidney function in patients with IgA nephropathy, and its continued approval is dependent upon confirmation of this clinical benefit. Results for this endpoint are expected in the final quarter of 2023 and are expected to support the traditional approval of Filspari.

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Efficacy and Safety of Filspari in Phase III Trial

Filspari is available as an oral medication taken once daily. Its mechanism of action is selective targeting of two major pathways involved in IgA nephropathy progression: endothelin-1 and angiotensin II.

The ongoing PROTECT Phase III trial is the largest interventional study to date on IgA nephropathy. This global, randomized, multicenter, double-blind, active-controlled clinical trial evaluates the safety and efficacy of sparsentan in 404 IgA nephropathy patients with persistent proteinuria, aged 18 years and older.

The interim results upon which the FDA’s accelerated approval is based demonstrate a rapid, consistent and clinically relevant reduction in proteinuria with 400 mg of sparsentan when compared to an active control (300 mg of irbesartan).

Interim results were announced by Travere Therapeutics in August 2021. The results demonstrated that after 36 weeks of treatment, patients receiving sparsentan showed a 49.8 percent mean reduction in proteinuria from baseline, compared to 15.1 percent mean reduction from baseline in irbesartan-treated patients (p<0.0001).

The efficacy data used for the FDA-approved label is based on post-hoc sensitivity analysis evaluating only the first 281 randomized patients in the trial. Ultimately, results were similar in the post-hoc analysis, with a 45 percent mean reduction in proteinuria from baseline for sparsentan-treated patients compared to a 15 percent reduction in the control group. Evidently, there is meaningful improvement with sparsentan.

Patients enrolled in the PROTECT study will continue with treatment and assessment in order to fully assess the effects of Filspari on eGFR (estimated glomerular filtration rate) slope over 110 weeks and understand its effects on kidney function decline.

Thus far, the safety results from the PROTECT study demonstrate that Filspari is well tolerated and has a well-defined safety profile that has been consistent across clinical trials involving the medication. The most common adverse reactions reported in PROTECT were peripheral edema, hypotension, dizziness, hyperkalemia and anemia. There are risks associated with birth defects and liver harm, so Filspari is only available through an FDA-approved Risk Evaluation and Mitigation Strategy.

A New Standard of Care for Rare Kidney Disease

Filspari has been available from the week of February 27^th, 2023, and Travere Therapeutics intends to assist patients throughout their treatment through a comprehensive patient support program. The approval of Filspari sets a stage for a better standard of care for patients with this rare kidney disease.

Eric Dube, PhD, president and CEO of Travere Therapeutics states that “Filspari has the potential to ultimately become the new standard of care for IgA nephropathy and offer hope to those living with this condition who until now have had few treatment options.”

Many individuals with IgA nephropathy do not respond to traditional treatments, which are predominantly hypertension medications like angiotensin-receptor blockers and angiotensin-converting enzyme inhibitors. As a result, many patients cannot properly manage their condition and the IgA nephropathy progresses more rapidly to kidney failure.

A treatment like Filspari has been long awaited and promises a better quality of life for patients, as IgA nephropathy is often associated with depression, fatigue, loss of work and social opportunities, and potential need for dialysis or kidney transplant.

The reported cost of Filspari is approximately $9,900 per month, amounting to between $70,000 and $100,000 per year.