The FDA has sunk Travere Therapeutics’ hopes of winning approval for its kidney disease candidate this year by requesting changes to the proposed risk evaluation mitigation strategy (REMS) that are expected to delay the decision date by three months.
Travere is seeking approval of the drug candidate, the dual endothelin angiotensin receptor antagonist sparsentan, in the treatment of the kidney disease IgA nephropathy. The FDA accepted the candidate for accelerated review, positioning Travere to learn its fate by Nov. 17, but then asked for the company to update its REMS to include liver monitoring. Travere expects the request to delay the decision date
Sparsentan has reached the cusp of FDA approval without causing alarm on the liver toxicity front but it is part of a class of medicines that has a history of safety issues. Pfizer pulled the endothelin receptor antagonist sitaxsentan from the market in 2010 over liver toxicity issues, and bosentan, sold by Johnson & Johnson as Tracleer, can cause severe liver injury.
More recently developed endothelin receptor antagonists have proven less troublesome. While a small percentage of patients on J&J’s Opsumit have experienced elevated liver enzymes, the increases haven’t led to clinically apparent acute liver injury. Even so, the label for Opsumit notes that similar drugs can cause liver problems and physicians are required to run liver enzyme tests before and during treatment.
It appears that sparsentan, like Opsumit before it, has been identified as a potential liver risk based on its association to other molecules, rather than because of evidence on the drug candidate itself. The FDA’s position took Travere by surprise, as CEO Eric Dube, Ph.D., explained in a statement.
“While this request for additional monitoring within the REMS came unexpectedly, the strength of the clinical data supporting the profile of sparsentan and our confidence in the potential for sparsentan to be approved as a new therapy for IgA nephropathy remain unchanged,” Dube said. “We will use the additional time to work collaboratively with the FDA as we continue the labeling process, and further prepare for launch with the goal of enabling sparsentan to ultimately become a new treatment standard.”