The company’s treatment for IgA nephropathy, sparsentan, failed to meet statistical significance by a measure of kidney function in a head-to-head confirmatory study versus irbesartan.
Pictured: Eric Dube, Travere CEO/Company Courtesy
Travere Therapeutics announced Thursday that its Phase III study to confirm the effectiveness of its kidney disease drug sparsentan, marketed as Filspari, narrowly missed one of its key endpoints.
The study looked at 404 patients with persistent proteinuria, or elevated protein levels in the urine, despite being in active angiotensin-converting enzyme inhibitor or angiotensin-receptor blocker treatment for IgA nephropathy (IgAN)—a kidney disease that results in protein build-up in a network of small blood vessels called the glomerulus. Patients received either sparsentan or the active control irbesartan, a standard treatment for the disease.
A preliminary review of the safety results at 110 weeks showed that the drug was “generally well-tolerated,” with a consistent safety profile between treatment groups, according to Travere’s announcement.
However, sparsentan’s efficacy findings were mixed.
While the drug “demonstrated long-term kidney function preservation and achieved a clinically meaningful difference in estimated glomerular filtration rate (eGFR)” compared to the control, it failed to demonstrate a statistically significant change in the eGFR total slope, which was a key endpoint in the study.
Sparsentan did, however, demonstrate statistically significant change in eGFR chronic slope—which is the mean rate of change after three months—“for purposes of regulatory review in the EU,” the company noted.
The drug is currently available under accelerated approval, which the FDA granted in February 2023, based on data suggesting sparsentan was more effective in reducing protein levels in urine than irbesartan. Initial data from the Phase III study published in April 2023 in The Lancet were promising, further suggesting sparsentan was more effective than irbesartan.
However, these latest results mean that Travere will be submitting a supplemental New Drug Application in the first half of 2024 with a view towards full U.S. approval.
“The confirmatory results of the PROTECT Study demonstrated treatment with Filspari resulted in the largest sustained reduction in proteinuria and one of the slowest rates of eGFR decline in a controlled study of IgAN patients, to date. This outcome is incredibly important for IgAN patients,” Travere CEO Eric Dube said in a statement.
Investors, however, were not as optimistic. Travere’s share price fell nearly 40% in pre-market trading on Thursday after making the announcement.
Nor is it the only bad news the company has received recently. Topline data from another Phase III study the company was conducting on the effectiveness of the drug in treating another rare kidney disease were similarly disappointing.
The study found sparsentan did not significantly improve kidney function in patients with focal segmental glomerulosclerosis (FSGS). In an investor call, Dube called the results “disappointing,” but also noted there may be a “rationale to engage with regulators to understand if there is a path to enable sparsentan to have a role in treating FSGS.”
Connor Lynch is a freelance writer based in Ottawa, Canada. Reach him at lynchjourno@gmail.com.
