The Food and Drug Administration (FDA) has granted accelerated approval to Filspari™ (sparsentan) to reduce proteinuria in adults with primary immunoglobulin A nephropathy (IgAN) at risk of rapid disease progression, generally a urine protein-to-creatinine ratio (UPCR) greater than or equal to 1.5g/g.
Sparsentan is an endothelin and angiotensin II receptor antagonist. Endothelin-1 and angiotensin II are thought to contribute to the pathogenesis of IgAN. The rare disease is characterized by the accumulation of IgA in the kidneys, which causes cellular changes within the glomeruli and damages the glomerular filtration barrier.
The accelerated approval was based on clinical trial data indicating a reduction of proteinuria. It has not been established whether sparsentan slows kidney function decline in patients with IgAN.
Results from the phase 3 PROTECT study (ClinicalTrials.gov Identifier: NCT03762850), showed that patients treated with sparsentan (n=141) achieved a mean reduction in proteinuria of 45% (95% CI, -51, -38) vs 15.1% (95% CI, -24, -4) with irbesartan (n=140) after 36 weeks of treatment (sparsentan vs irbesartan: ratio of adjusted geometric mean relative to baseline at week 36, 0.65 [95% CI, 0.55-0.77]; P <.0001).
Patients included in the study had biopsy-proven IgAN, eGFR greater than or equal to 30mL/min/1.73 m2, and total urine protein greater than or equal to 1.0g/day on a maximized stable dose of renin-angiotensin system inhibitor treatment that was at least 50% of maximum labeled dose. The mean age was 46 years, 69% were male, 62% were White, 35% Asian, and 1% Black or African American. Mean (SD) baseline eGFR was 56 (24)mL/min/1.73 m2. Treatment effect on UPCR at 36 weeks was observed to be consistent across subgroups including age, sex, race, and baseline eGFR and proteinuria levels.
“Today’s approval of Filspari sets the stage for a new standard of care for IgA nephropathy patients,” said Dr Brad Rovin, MD, Medical Director at Ohio State University Center for Clinical Research Management, Director of the Division for Nephrology, and steering committee member for the PROTECT clinical trial. “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. The approval of this innovative treatment is founded in data from the largest head-to-head phase 3 clinical trial in IgA nephropathy.”
Continued approval of this indication is contingent upon data from a confirmatory trial. The PROTECT study will continue in a blinded manner over 110 weeks to assess the treatment effect of sparsentan on eGFR slope; results of the confirmatory endpoint analysis are expected in the fourth quarter of 2023.
As for safety, the most common adverse reactions reported were peripheral edema, hypotension, dizziness, hyperkalemia, and anemia. The labeling for Filspari also includes a Boxed Warning regarding the risk of hepatotoxicity and embryo-fetal toxicity. As such, the medication is only available through a restricted distribution program called the Filspari Risk Evaluation and Mitigation Strategy (REMS).
Filspari is supplied as 200mg and 400mg tablets. The product is expected to be available beginning the week of February 27, 2023.
- Travere Therapeutics announces FDA accelerated approval of Filspariᵀᴹ (sparsentan), the first and only non-immunosuppressive therapy for the reduction of proteinuria in IgA nephropathy. News release. Travere Therapeutics. February 17, 2023. https://ir.travere.com/news-releases/news-release-details/travere-therapeutics-announces-fda-accelerated-approval.
- Filspari. Package insert. Travere Therapeutics; 2023. Accessed February 21, 2023. https://travere.com/wp-content/uploads/2023/02/filspari-final-uspi-20230217.pdf.
This article originally appeared on MPR