Despite trial scare, Travere's Filspari gets full FDA approval in kidney disease battle with Novartis

Travere Therapeutics has achieved a significant milestone with the FDA granting full approval for its drug Filspari in the treatment of IgA nephropathy (IgAN), a rare autoimmune kidney disease. This approval comes a year after the company missed a trial endpoint, causing much relief for Travere. The FDA also removed a specific urine protein level requirement from Filspari’s label, making the drug accessible to a broader range of patients at risk of disease progression.

Travere's CEO, Eric Dube, Ph.D., emphasized that the label adjustment enables Filspari to reach more patients who may have lower risks of disease progression. This change is expected to boost physician confidence in prescribing the drug, potentially increasing its adoption among nephrologists. According to Dube, full approval acts as a crucial element during a drug's launch, encouraging later adopters who seek approval and support from guidelines and peers.

Filspari initially received accelerated approval in February 2023 based on phase 3 trial data demonstrating significant reductions in proteinuria compared to irbesartan after 36 weeks of treatment. As proteinuria is a key indicator of kidney function, this reduction was critical. Notably, Filspari is the first non-immunosuppressive medication approved for IgAN, and the company originally aimed for full approval based on long-term kidney function outcomes measured by the estimated glomerular filtration rate (eGFR). However, the trial, named PROTECT, narrowly missed statistical significance on this endpoint, prompting Travere to seek full approval based on consistent treatment effects across various measurements and positive FDA feedback.

The full approval hinges on a modified analysis of 404 randomized patients, including those who discontinued treatment early. In this new analysis, Filspari significantly slowed the rate of decline in kidney function from baseline to Week 110 compared to irbesartan. The average eGFR slope was -3.0 mL/min/1.73 m2/year for Filspari and -4.2 mL/min/1.73 m2/year for irbesartan, showing a statistically significant difference.

The competitive landscape for IgAN treatments has become more crowded since Travere’s eGFR readout. Calliditas Therapeutics’ Tarpeyo received full FDA approval in December 2023, and Novartis’ complement inhibitor Fabhalta gained accelerated approval in August. Although Tarpeyo, which uses a steroid approach, is not seen as a direct competitor, Novartis’ selective ETA receptor inhibitor, atrasentan, presents more direct competition.

Despite these new entrants, Filspari has distinct advantages. Unlike Novartis’ drugs, which are add-ons to existing treatments, Filspari offers a dual mechanism of action in a single tablet. This simplifies the treatment regimen for patients and provides doctors with the assurance that patients are adherent to their medication. According to Dube, fewer and more effective medicines benefit young patients who have decades ahead of them, reducing pill burden and improving compliance.

However, a downside remains: the FDA's full approval still includes a liver monitoring requirement due to potential liver toxicity risks. Patients must undergo monthly liver function tests for the first year followed by quarterly tests. Unlike Filspari, Novartis' Fabhalta does not have this warning. Despite this, Travere believes that educating healthcare providers and patients about safety measures upfront will support Filspari's uptake. The company is also gathering real-world data to potentially request the FDA to revise the liver monitoring requirement in the future.

Filspari's market performance has been strong, with second-quarter sales reaching $27.1 million, surpassing expectations. Travere is also investigating potential combinations for Filspari, including with SGLT-2 inhibitors in IgAN, and remains committed to exploring its use in other kidney diseases like focal segmental glomerulosclerosis (FSGS). A global project named PARASOL is evaluating the relationship between proteinuria and kidney failure in FSGS, which could lead to further regulatory approvals.

Through these efforts, Travere aims to solidify Filspari's place in the treatment landscape, offering hope to patients with serious kidney conditions.

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