The FDA granted accelerated approval Friday to Travere Therapeutics’ sparsentan, now to be marketed as Filspari, to reduce the burden of proteinuria in adults with primary IgA nephropathy.
Eric Dube, Travere CEO/Company Courtesy
The FDA granted accelerated approval Friday to Travere Therapeutics’ sparsentan, now to be marketed as Filspari, to reduce the burden of proteinuria in adults with primary IgA nephropathy (IgAN).
Filspari is the first non-immunosuppressive treatment approved for IgAN. Under the accelerated approval, Travere is required to run a Risk Evaluation Mitigation Strategies (REMS) program, which will involve training for prescribers and monitoring for patients. Pharmacies can only dispense Filspari to patients who are in the REMS program and are cleared to receive the drug.
The drug is indicated for patients who are likely to see rapid disease progression, “generally a urine protein-to-creatinine ratio (UPCR) ≥1.5 g/g,” according to its label. The FDA also included a warning about liver and embryo-fetal toxicities on Filspari’s label.
Filspari is a “first-of-its-kind, non-immunosuppressive therapy” for IgAN and could potentially become “the new standard of care” for this condition, Eric Dube, Ph.D., president and CEO, Travere, said in a statement.
Designed to be taken once daily, Filspari works by blocking endothelin-1 and angiotensin II, which are involved in disease progression.
Its accelerated approval was based on promising interim results from the ongoing Phase III PROTECT study, wherein the drug significantly reduced proteinuria after 36 weeks of treatment. Filspari was more than three times as effective as the active comparator Avapro (irbesartan).
Travere first submitted the New Drug Application for Filspari in March 2021 and initially expected a verdict on Nov. 17, 2022. But in October 2022, the FDA requested the REMS program, which pushed the target action date back by three months.
Continued approval of Filspari will depend on its confirmatory Phase III study PROTECT results, which seeks to determine whether the drug can slow kidney function decline. Results for this study are expected in the fourth quarter of 2023 and will support Filspari’s traditional approval.
Other Players in the IgAN Arena
IgAN is a rare autoimmune disease that afflicts the kidneys. It typically manifests as bloody or discolored urine and progresses into lower back pain, edema, chronic kidney disease and kidney failure.
Aside from Travere, several other biopharma companies are working on a solution for IgAN.
Last month, Vera Therapeutics’ atacicept met its primary endpoint in the Phase IIb ORIGIN trial, reducing UPCR by 31% relative to baseline at 24 weeks. While statistically significant, investors appeared to be underwhelmed and the company’s stocks fell 65% after the data drop.
While cross-trial comparisons are fraught, Vera’s competitors have produced more compelling efficacy numbers for their respective IgAN hopefuls. Ionis and Roche, for example, have shown that their IONIS-FB-LRx candidate can decrease 24-hour urinary protein concentrations by 44% on average after 29 weeks of treatment. The partners are gunning for a Phase III study in 2023.
Meanwhile, Chinook Therapeutics is developing its endothelin receptor antagonist atrasentan, which demonstrated a 38.1% reduction in proteinuria at six weeks, which improved to 48.3% and 54.7% at 12 and 24 weeks, respectively, Phase II basket trial AFFINITY.
Atrasentan is also being studied in the Phase III ALIGN trial, from which the company expects topline data in the third quarter of 2023. A New Drug Application submission for atrasentan, under the accelerated approval pathway, will follow.
