Officials with the FDA have approved chenodiol (Ctexli; Mirum) for the treatment of cerebrotendinous xanthomatosis (CTX) in adults, making it the first FDA-approved therapy to address this rare lipid storage disease.1
CTX is a genetic metabolic disorder caused by a mutation in a gene called CYP27A1, resulting in a deficiency of the enzyme that is important in the body’s ability to break down fats. Due to reduced bile acid production in the liver, patients with CTX are unable to break down cholesterol in a normal way, resulting in the deposition of atypical cholesterol metabolites in various places in the body. Chenodiol works to replace deficient levels of one of the bile acids, reducing the abnormal deposits of cholesterol metabolites thought to be responsible for clinical abnormalities in CTX.
The approval was based, in part, on results from a 24-week, double-blind, placebo-controlled, randomized crossover withdrawal trial, which demonstrated that treatment with a 250-mg 3-times-daily treatment with chenodiol resulted in significant reduction in plasma cholestanol and urine 23S-pentol compared with placebo.
The prescribing information for this treatment includes a warning for liver toxicity in all patients with increased risk for liver damage in patients with preexisting liver disease or bile duct abnormalities.
The most common adverse events in the clinical trial were diarrhea, headache, abdominal pain, constipation, hypertension, muscular weakness, and upper respiratory tract infection.
“The FDA is dedicated to supporting new drug development for rare diseases including very rare metabolic diseases like cerebrotendinous xanthomatosis,” said Janet Maynard, MD, MHS, director of the Office of Rare Diseases, Pediatrics, Urologic and Reproductive Medicine, in the FDA’s Center for Drug Evaluation and Research. “CTX is a progressive multisystemic disorder that significantly impacts patients and previously lacked approved treatments. Today’s approval provides a safe and effective treatment option for CTX.”
Reference
- Food and Drug Administration. FDA approves first treatment for cerebrotendinous xanthomatosis, a rare lipid storage disease [press release]. February 21, 2025. Accessed April 9, 2025. www.fda.gov/news-events/press-announcements/fda-approves-first-treatment-cerebrotendinous-xanthomatosis-rare-lipid-storage-disease