Years after cutting ties to its disgraced founder, Martin Shkreli, and after navigating a short regulatory hiccup, Travere Therapeutics has won an FDA approval for a first-of-its-kind drug for a rare kidney disease.
The drug, called sparsentan, snagged an FDA accelerated approval Friday to treat patients with primary immunoglobulin A nephropathy (IgAN) who are at risk of rapid disease progression. Now bearing the commercial moniker Filspari, the drug is the first non-immunosuppressive therapy approved for IgAN.
In a Saturday note to clients, analysts at Evercore ISI said they believe Filspari could become a blockbuster drug.
Boasting a unique mechanism of action, Filspari works by blocking both endothelin and angiotensin receptors, Travere CEO Eric Dube explained in an interview ahead of the approval.
That feature separates Filspari from angiotensin-targeting ACE inhibitors and ARBs, which are popular drugs mainly used to treat high blood pressure and have been repurposed for IgAN because of their ability to lower blood pressure in the kidney. The mechanism also differentiates Filspari from endothelin receptor antagonists such as Johnson & Johnson’s pulmonary arterial hypertension med Tracleer.
There’s also Calliditas Therapeutics’ Tarpeyo, a formulation of the popular corticosteroid budesonide, which in late 2021 became the first drug specifically approved by the FDA for IgAN. But Dube said doctors and patients typically don’t want to use steroids because of side effects.
About 90% of patients diagnosed with IgAN are currently on ACE inhibitor or an ARB. But for patients who have more severe and progressive disease, blocking angiotensin itself isn’t enough, Dube said.
During the initial phase of Filspari’s launch, Travere plans to target patients who are at high risk of progressing and losing a kidney, Dube said. Between 30,000 and 50,000 patients in the U.S. fit that description, by Travere's estimate.
Unlike many other rare diseases, where patients are diagnosed and managed by a few specialists at large academic centers, IgAN patients are typically treated at community practices, Dube noted. Travere is targeting 6,000 U.S. nephrologists who currently care for about 90% of severe IgAN patients, he added.
Aside from Filspari, Travere sells kidney stone therapy Thiola and already has relationships with about 2,000 nephrologists. The company further expanded its commercial infrastructure last year, so Dube suggested the company can quickly execute its launch plan for Filspari.
“Our goal is really to replace the role that ACE or ARB has played as the foundational treatment,” the Travere CEO said.
The FDA doled out the accelerated approval based on data from the phase 3 PROTECT trial, which showed Filspari significantly reduced proteinuria compared with irbesartan, an ARB, after 36 weeks of treatment. Patients on Filspari achieved mean proteinuria reductions of 49.8% from baseline, versus a 15.1% reduction for the control group.
Meanwhile, Travere is still running the PROTECT trial. Later this year, the company expects to report two-year proteinuria data and—perhaps more importantly—kidney function outcomes as measured by the estimated glomerular filtration rate (eGFR). Those results could support a potential full approval.
On the safety side, J&J’s Tracleer and other similar drugs have been linked to liver injury. Although Filspari itself hasn’t shown any severe liver toxicity, the FDA has requested a special safety program known as risk evaluation mitigation strategy (REMS) for Filspari to include liver monitoring. The adjustment caused a three-month delay to the FDA’s decision for Filspari.
Filspari’s required liver monitoring frequency—initially once very month and then quarterly—is not a barrier to adoption, the Evercore analysts wrote in their Saturday note, citing nephrologists' feedback.
Because of a risk for embryo fetal toxicity, the drug’s REMS program also includes required monitoring for women who could become pregnant.
Travere has come a long way to this approval. The company was once called Retrophin but rebranded in 2020 to free itself from any ties with its founder, the “pharma bro” Martin Shkreli. As for Filspari, the drug has changed hands many times. It was originally developed by Bristol Myers Squibb and then licensed to Pharmacopeia, which was acquired by Ligand Pharmaceuticals. Travere got the drug from Ligand in 2012.
Outside of the U.S., Travere has partnered with CSL Vifor in Europe, Australia and New Zealand. The European Medicines Agency in August accepted CSL’s application for review.
Dube said he also sees potential for combining Filspari with other agents, mostly notably SGLT-2 inhibitors such as AstraZeneca’s Farxiga, which have recently shown good data in chronic kidney disease. Travere is updating the open-label expansion phase of the PROTECT trial to include SGLT-2 combinations with Filspari.
Travere’s market research suggests nephrologists predict that Filspari and SGLT-2 combos are likely to become a force in the future because they’re both once-a-day oral medicines with strong efficacy, Dube said.
Besides IgAN, Travere is also developing Filspari for focal segmental glomerulosclerosis (FSGS), an even rarer kidney disease in which scar tissue develops on the kidney’s waste filter glomeruli.
The company recently had a setback in FSGS. Instead of an accelerated approval, the FDA earlier this year asked Travere to wait for the full two-year data from the pivotal DUPLEX study—which has a very similar design to the PROTECT trial in IgAN—to apply for a full approval.
It’s not a significant delay, though. Travere expects to report those data in the second quarter and looks to file for an approval by the end of this year, Dube said.
Editor's Note: The story has been updated with additional comments from an Evercore ISI note.