Primary IgA nephropathy : FDA grants full approval to Travere Therapeutics’ Filspari

In a groundbreaking move, the US Food and Drug Administration (FDA) has granted full approval to Travere Therapeutics’ Filspari (sparsentan) for treating primary IgA nephropathy (IgAN) in adults at risk of disease progression. This decision, announced on September 5, 2024, marks a significant milestone in the battle against this rare kidney disease, offering a new non-immunosuppressive option that has demonstrated superior efficacy in slowing the decline of kidney function compared to the standard treatment, irbesartan.

Travere Therapeutics had previously received accelerated approval for Filspari in February 2023 based on the surrogate marker of proteinuria reduction, a key indicator of kidney damage in IgAN. However, the recent full approval is grounded in the positive outcomes from the Phase 3 PROTECT Study, which is the largest head-to-head interventional study conducted in IgAN. The study assessed the safety and efficacy of 400 mg of Filspari against 300 mg of irbesartan in a global, randomised, multicentre, double-blind, parallel-arm, active-controlled clinical trial involving 404 adult patients aged 18 and older.

New hope for patients with primary IgA nephropathy

Primary IgA nephropathy, also known as Berger’s disease, is a rare and serious condition where IgA, a protein that helps the body fight infections, deposits in the kidneys, causing inflammation that can lead to kidney damage over time. For years, there have been limited treatment options for this disease, making Filspari a significant development in nephrology.

The PROTECT Study, which formed the basis for Filspari’s full approval, provided compelling evidence of the drug’s efficacy. Over a two-year period, Filspari significantly slowed the decline in kidney function compared to irbesartan, with a 3.8 mL/min/1.73 m² difference in the mean change from baseline by Week 110. Additionally, patients treated with Filspari experienced a mean reduction in proteinuria of 49.8% from baseline after 36 weeks, compared to just a 15.1% reduction in those receiving irbesartan. This result was crucial in proving the long-term benefits of Filspari and securing its full approval.

A breakthrough in non-immunosuppressive treatment

Filspari is the first and only oral, once-daily, non-immunosuppressive medication specifically designed to target two key pathways involved in IgA nephropathy progression, endothelin receptor antagonism and angiotensin II receptor blockade. This dual mechanism sets it apart from other treatments that predominantly focus on reducing proteinuria but do not necessarily address the root causes of kidney damage.

The full approval of Filspari provides a more definitive treatment option for physicians and patients. Many people living with IgAN are at risk of disease progression and are seeking safe, effective, and convenient treatment alternatives that can help preserve their kidney function. With this full approval, healthcare providers can now confidently prescribe Filspari to more patients, potentially replacing the current standard of care with a treatment that offers superior kidney function preservation.

Addressing safety concerns with REMS program

Despite its groundbreaking benefits, Filspari is not without risks. The FDA approval includes a Risk Evaluation and Mitigation Strategy (REMS) due to concerns about hepatotoxicity and embryo-fetal toxicity. Patients who are prescribed Filspari must undergo regular liver function tests and pregnancy screenings to mitigate these risks. Travere Therapeutics is also planning to submit a supplemental New Drug Application (sNDA) to potentially modify the liver-monitoring requirements under the REMS program, enhancing the safety profile of Filspari for a broader patient population.

What does this mean for the future of IgAN treatment?

The full approval of Filspari represents a significant leap forward in treating IgAN and sets a new standard for clinical trials involving rare kidney diseases. As the only non-immunosuppressive drug to demonstrate such robust results, Filspari may encourage further innovation in nephrology, especially for conditions that have lacked effective treatments. Meanwhile, the IgAN community, which has already benefited from the approval of Calliditas Therapeutics’ Tarpeyo (budesonide) in December 2023, now has another potent tool to fight against this challenging disease.