A Travere Therapeutics drug that won speedy approval early this year for a rare autoimmune kidney disorder has failed to meet the key goal of its confirmatory study. Still, the biotech points to data trends favoring patients treated with its drug, Filspari, and it aims to seek full approval. But even if the FDA permits the drug to remain on the market, the disappointing trial results reported Thursday call into question the commercial prospects of a product once projected to become a blockbuster seller.

Filspari was developed to treat immunoglobulin A nephropathy (IgAN), in which the buildup of antibodies in the kidneys damages these organs. The FDA awarded accelerated approval for Travere’s small molecule based on preliminary Phase 3 data showing the drug led to statistically significant reductions in levels of proteins in the urine that are signs of conditions affecting the kidneys. This so-called surrogate endpoint is an indicator the drug might be working. To confirm patient benefit, Filspari’s Phase 3 trial continued to assess kidney function. It’s here Filspari fell short.

The two-year Phase 3 study compared the Travere drug to irbesartan, a generic blood pressure drug that is also used to slow the progression of nephropathy. The key confirmatory benchmark in the 404-patient study is estimated glomerular filtration rate (eGFR), a measure of kidney function. The trial took measures of eGFR from day 1 of treatment through week 110. Over that period of time, the slope of these measures favored Filspari, as the study drug arm showed slower rates of kidney function decline. But even though these results were clinically meaningful for patients, compared to the irbesartan arm, they were just short of statistical significance.

The Travere drug is still under review in Europe, where regulators have set a confirmatory endpoint of eGFR measured from week 6 to week 110. On this measure, the preliminary data show Filspari achieved statistical significance. CSL Vifor holds rights to commercialize Filspari in Europe, Australia, and New Zealand.

Travere frames the preliminary Phase 3 data in the best possible light, saying the results suggest Filspari offers potential long-term benefit for IgAN patients. The company said it will work with study investigators to evaluate the data. It also plans to present the results at an upcoming medical meeting and publish them in a peer-reviewed journal. Company executives plan to meet with regulators with the goal of readying an application in the first half of 2024 seeking full FDA approval.

Filspari’s February FDA nod made it the second approved IgAN therapy, following Calliditas Therapeutics drug Tarpeyo. But Tarpeyo works by suppressing the immune system throughout the body. Travere’s molecule is designed to selectively block two pathways associated with the progression of chronic kidney diseases, including IgAN. Its advantage is a mechanism of action that does not suppress the immune system. Companies such as Vera Therapeutics and Human Immunology Biosciences are also developing IgAN drugs that don’t have a broad immunosuppressive effect. Meanwhile, Novartis added two IgAN drug candidates to its pipeline via the $3.2 billion acquisition of Chinook Therapeutics. The Chinook acquisition closed last month.

The Phase 3 results are the latest disappointing news for Filspari, a drug that Travere has said could potentially treat multiple kidney disorders. In May, the company reported the drug failed a pivotal study in the rare kidney disease focal segmental glomerulosclerosis, or FSGS. Similar to the results of the IgAN study, the eGFR improvement in the Filspari arm was not enough to be statistically significant compared to the irbesartan group.

In a note sent to investors, William Blair analyst Tim Lugo wrote that the historically strong performance of irbesartan ultimately hurt the ability of Filspari to achieve the confirmatory goal of its IgAN test. The overall results point toward the Travere drug’s efficacy, and the firm does not believe there’s enough in the data to justify the FDA removing the product from the market, he said. But Lugo added that the lack of a clear competitive benefit gives payers little incentive to cover Filspari over irbesartan, making the Travere drug’s commercial opportunity uncertain.

“While these top-line data appear to clearly show a treatment benefit with Filspari, we believe the magnitude of effect is somewhat underwhelming, especially in light of an increasingly competitive landscape, and the narrow miss of statistical significance on the primary endpoint now raises the commercial risk in the United States,” Lugo said.

Travere reported Filspari generated $3.5 million in sales in the second quarter of this year, and $6.5 million since its FDA approval. As of the end of June, Travere’s cash position was $491.3 million. The company’s stock price closed Thursday at $7.64, down 40.6%.

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