FDA issues Untitled Letter to Travere Therapeutics over visual aid for kidney disease drug Filspari

The Food and Drug Administration isn't slowing down its Untitled Letter spree as fall begins. The FDA's Office of Prescription Drug Promotion sent Travere Therapeutics a letter over its advertising for Filspari, a drug that's approved to slow kidney function decline in people with primary IgA nephropathy (IgAN) as well as reduce abnormal levels of urine protein in people with focal segmented glomerulosclerosis (FSGS). The OPDP letter was issued on July 28 and addressed to Travere's director of regulatory affairs Rexner Vargas. It comes nearly one year after the Department of Health and Human Services and the FDA announced its crackdown on pharma ads. This letter takes aim at a professional visual aid for the drug, arguing it's false or misleading. The visual aid, intended for physicians, shows a tree shaped like kidneys combining two colors with 'a stronger foundation for kidney preservation' in large letters at the top. The aid urges physicians to 'replace your patients' RAS inhibitor with dual-acting Filspari.' The FDA highlighted certain claims as misleading — such as that the drug leads to a 'stronger foundation for kidney preservation' and that achieving 'complete remission of proteinuria (defined as <0.3 g/d) drives long-term nephroprotective benefits.' The agency also took issue with Travere's claims that the drug is 'proven to achieve better kidney function preservation over two years.' These claims are misleading, the FDA argued, because those outcomes have not been demonstrated in the clinical data. The prescribing information (PI) that's approved by the FDA states that the drug is indicated to slow kidney function decline in adults with primary immunoglobulin A nephropathy (IgAN) who are at risk for disease progression. In the clinical studies section of the PI, Filspari has been shown to reduce the rate of decline in kidney function from baseline to week 110 compared to irbesartan, a drug that treats kidney function in type 2 diabetes patients. Yet while it slows the decline in kidney function, this still occurs in people taking Filspari. 'Therefore, claims suggesting that treatment with Filspari will result in kidney preservation, kidney function preservation, or nephroprotection are misleading,' the FDA concluded. The letter was coauthored by Susannah O'Donnell, MPH, RAC, the acting deputy director in the division of advertising and promotion review at OPDP, as well as Koung Lee, RPh, MSHS, a regulatory review officer. The letter also singled out a bar graph that states the drug is 'proven to drive 3x more patients to complete remission of proteinuria' and 'proven to drive 3x more patients to complete remission of proteinuria.' However, these claims are misleading, the FDA argued, because it's not possible to determine based on the clinical data that Filspari is actually proven to result in complete remission of proteinuria. The FDA also targeted some safety and risk claims, in particular that Filspari 'was well tolerated over two years.' The claims minimize the risks associated with the drug, the FDA stated, which included Boxed Warnings of hepatotoxicity and embryo-fetal toxicity. The drug has some warnings and precautions about how the drug affects blood pressure, including a greater incidence of hypotension-associated adverse events, compared to patients on irbesartan. Yet the visual aid claims that 'blood pressure remained consistent over a two year period and was comparable to irbesartan.' As with other Untitled Letters from the FDA, Travere Therapeutics must take immediate action to address any violations and submit a written response to the letter within 15 working days. Travere did not immediately respond to a request for comment. While most of the FDA letters have targeted pharma TV ads, several have taken aim at peripheral promotions like webpages and virtual meeting backgrounds. The Travere letter was disclosed after an Untitled Letter was sent to Alar Pharmaceuticals over its communications around an unapproved ketamine drug at the American Psychiatric Association (APA)'s annual meeting. The Alar Untitled Letter flagged an exhibit booth and brochure at the APA meeting that provided details about ALA-3000, a ketamine pamoate injection, which the FDA said crossed the line from scientific information to promotion of an unapproved drug.