The outcome of the third phase was negative, and from a seemingly tightening regulatory environment to a grueling three-month review extension, Travele Therapeutics’ path in the pioneer bid was anything but certain. However, the company defied the odds and won breakthrough FDA approval for Filspari in focal segmental glomerulosclerosis (FSGS), providing the first treatment for a rare kidney disease.
Monday’s FDA approval makes Filspari the first treatment specifically indicated for FSGS, presenting FSGS with a sales opportunity of more than $1 billion, according to analysts at Leerink Partners. The drug was originally approved in 2023 to treat another kidney disease, IgA nephropathy.
FSGS is estimated to affect more than 40,000 patients in the United States. The disease is characterized by scarring of the kidney’s filtration unit as proteins continue to leak into the urine, often leading to further disease progression and kidney failure, sometimes progressing very rapidly.
Filspari is currently shown to reduce proteinuria in FSGS patients aged 8 years and older without nephrotic syndrome. This means more than 30,000 patients in the U.S. could immediately benefit from Filspari, Travere CEO Dr. Eric Dube told Fierce Pharma.
Three criteria are needed to determine that a patient has nephrotic syndrome, and the patient is sicker, explained Dr. Gyula Inrig, chief medical officer at Travele, in the same interview with Fierce. The normal level is about 30 mg, but the patient must have a fairly high concentration of urine protein, at least 3.5 g per day. At the same time, the albumin protein in the patient’s blood must decrease and the body must be swollen.
Patients with active nephrotic syndrome who improve after treatment with standard immunosuppressants may still be eligible for Filspari, Inrig noted.
It was a big win for Travele, and the FSGS green light was the traditional full approval. This follows several controversial FDA decisions that have raised concerns that the agency’s oversight in the rare disease field may increase. However, recently the pendulum appears to be swinging back toward greater regulatory flexibility. FSGS’ Filspari joins Denali Therapeutics’ Hunter syndrome treatment Avraya and Rocket Pharmaceuticals’ hematopoietic stem cell-based gene therapy Cresradi, among other drugs recently approved by the FDA to treat rare diseases.
The approval covers “various” types of FSGS, including primary, secondary, genetic and unknown causes, Dube said.
Mr. Travelet had a tough time getting Monday’s confirmation. FSGS’ decision was delayed for three months after the FDA requested additional information from the company to further characterize Filspari’s clinical benefits. The request was not surprising given the changes to the primary endpoint under review, Dube explained to Fiers in a separate interview prior to approval.
For the first-of-its-kind indication, Travelle urged the FDA to essentially build on Phase 3 failures on certain primary endpoints and instead focus on newly emerging alternatives that FDA officials helped shape.
Back in 2023, Travere found that a phase 3 duplex trial pitting Filspari against off-label use of irbesartan, a drug sold by Sanofi as Avapro, failed to meet its primary endpoint of change in estimated glomerular filtration rate (eGFR), a measure of kidney function over time, after two years. Favorable differences did not meet statistical significance.
Nevertheless, this study, like Phase 2 before it, demonstrated Filspari’s ability to reduce the presence of excess protein in the urine, or proteinuria. At a prespecified interim analysis at week 36, approximately 42% of patients had partial remission of proteinuria. This is defined as a urinary protein-to-creatinine ratio (UPCR) of 1.5 or less and a >40% decrease from baseline. This rate was significantly better than the 26% recorded in the irbesartan group, according to the results published in the New England Journal of Medicine.
Complete remission, defined as UPCR <0.3 at any time during the double-blind period, was more common with Filspari (18.5%) than with irbesartan (7.5%).
Additionally, 12 patients (6.5%) in the Filspari group and 21 patients (11.2%) in the control group had renal failure. Travert, using Britain’s National Registry of Rare Kidney Diseases, which bills itself as the largest of its kind in the world, estimated that this level of treatment efficacy would translate into a 24% reduction in the risk of kidney failure if patients were followed for five years, Inrig said in an interview with Fiers before approval.
Less than 20% of patients with nephrotic syndrome participated in the Duplex trial. While these patients also appear to benefit from Filspari, patients without this diagnosis experienced greater treatment effects across the study’s endpoints, Inrig said. As a result, the FDA limited approvals to exclude the nephrotic subgroup, Inrig said.
Across the study population, patients treated with Filspari experienced a statistically significant 46% reduction in proteinuria from baseline to week 108. compared to 30% in patients treated with the highest labeled dose of irbesartan. In patients without nephrotic syndrome, Filspari reduced proteinuria by 48% compared with irbesartan by 27%.
Duplex’s positive data led to the establishment of a PARASOL working group to elucidate endpoint selection for FSGS clinical trials, despite the primary endpoint miss. With participation from the FDA, this group found that eGFR slope is not an ideal endpoint for FSGS given the heterogeneity of the disease. To show a clinically meaningful and statistically significant effect on that measure, a trial would need nearly 2,000 patients, a requirement that is not feasible for rare diseases, Inrig said. Instead, the research group found that proteinuria behaved similarly across patient subgroups, thus potentially aiding regulatory approval.
The FDA’s position became clearer about a year ago when Dimerix and its new partner, Amicus Therapeutics, announced that the agency had agreed to use proteinuria as an appropriate primary endpoint in the prior approval of a competing FSGS candidate, DMX-200.
Adding further optimism to Travere’s case, the FDA canceled an advisory committee meeting scheduled for September.
But toward the end of the year, accusations began to surface among rare disease drug developers that the FDA was backtracking on previously agreed upon clinical development and regulatory plans. Against this backdrop, news of a three-month extension for Filspari arrived in January, raising questions about the drug’s fate despite the FDA’s involvement in the PARASOL project.
Dubé said there have also been changes to the FDA’s Filspari review team in recent years, with several new names included in the FDA’s request for information on Travele. But Dr. Aliza Thompson, who was promoted last year to head of the FDA’s Division of Cardiology and Nephrology, who is in charge of reviewing Filspari, has been with the agency for a long time.
Meanwhile, Filspari has managed to maintain its position in IgAN despite increasing competition, including two drugs from Novartis. Filspari’s full-year sales in 2025 increased 144% year-on-year to $322 million.
The FDA recently adjusted liver monitoring requirements for Filspari, which simplifies access by allowing patients to adjust the frequency of monitoring to every three months to match how they track their kidney health, Dubé said.
Dube confirmed that the liver monitoring obligation also applies to FSGS indications, stressing that it is not an obstacle for doctors. In any case, most doctors are already familiar with Filspari, the CEO said, noting that there is more than 85% overlap in the proportion of doctors treating the two conditions.
Additionally, last year’s KDIGO guideline update for IgAN recommended the use of Filspari, a dual endothelin-angiotensin receptor antagonist, rather than traditional renin-angiotensin system (RAS) inhibition as first-line treatment. The guidelines also mention the possibility of combining Filspari with immune-targeted therapies for patients with more difficult-to-treat diseases.
“There are other treatments available, but we are in a unique position and can be used in combination,” Dube said. “This is why demand for Filspari is accelerating, and we expect its use to continue to grow even as other treatments emerge this year.”
