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FDA Approves Chenodiol Tablets for Cerebrotendinous Xanthomatosis
With this FDA approval, chenodiol tablets become the first approved drug to treat CTX, a rare lipid storage disease.
The US Food and Drug Administration (FDA) has approved chenodiol tablets (Ctexli) for the treatment of adults with cerebrotendinous xanthomatosis (CTX), marking the first approved treatment for the rare genetic lipid storage disease.1
Announced on February 21, 2025, the approval was awarded to Mirum Pharmaceuticals based on positive results from the Phase 3 RESTORE study, in which chenodiol reduced bile alcohols with high statistical significance (P <0.0001) in patients with CTX.
“CTX is a progressive multisystemic disorder that significantly impacts patients and previously lacked approved treatments,” said Janet Maynard, MD, director of the Office of Rare Diseases, Pediatrics, Urologic, and Reproductive Medicine in the FDA Center for Drug Evaluation and Research (CDER). “Today’s approval provides a safe and effective treatment option for CTX.”
A genetic metabolic disorder, CTX is caused by a mutation in the CYP27A1 gene resulting in a deficiency in the ability to break down fats. Affected by reduced production of the bile acid CDCA in the liver, patients with CTX experience a buildup of bile alcohols which precede the toxic accumulation of cholestanol across the brain, liver, skin, and tendons. These deposits can severely damage these organs and related tissue, and lead to irreversible neurologic dysfunction.
Chenodiol is designed to replace deficient levels of these bile acids, and ultimately reduce abnormal deposits of cholesterol metabolites deemed responsible for clinical abnormalities in CTX. Mirum Pharmaceuticals submitted a New Drug Application (NDA) to the FDA in June 2024, based on positive results from the RESTORE study.
A double-blind, placebo-controlled, randomized crossover withdrawal trial, RESTORE evaluated the safety and efficacy of chenodiol administered at 250 mg 3 times daily in tablet format. Investigators measured the change in blood and urine biomarkers associated with CTX across a screening period (4 weeks), 4 treatment periods (6 months), and a follow-up phone call (30 days after the last dose.
Analyses showed the study met its primary endpoint, achieving a reduction in bile alcohols with high statistical significance (P <.0001). Mirum Pharmaceuticals indicated the difference between active chenodiol and placebo at the end of the randomized double-blind withdrawal period was 20-fold. Further improvements in serum cholestanol were also reported with chenodiol treatment.
Regulators added a warning for liver toxicity in the prescribing information for chenodiol, for all patients with increased risk for liver damage after a history of liver disease or bile duct abnormalities. The FDA urged patients to obtain liver blood tests before initiation and annually on treatment or as clinically indicated.
Safety data showed the most common side effects of chenodiol were diarrhea, headache, abdominal pain, constipation, hypertension, muscular weakness, and upper respiratory tract infection. The FDA advised the discontinuation of the drug if patients experience any signs of liver toxicity, including nausea, fatigue, or yellowing of the eyes and skin.
The agency previously granted Priority Review, Fast Track, and Orphan Drug designations to chenodiol for the treatment of CTX.
“The FDA is dedicated to supporting new drug development for rare diseases, including very rare metabolic diseases like CTX,” Maynard added.
References
Commissioner of the FDA. FDA approves first treatment for cerebrotendinous xanthomatosis, a rare lipid storage disease. U.S. Food and Drug Administration. February 21, 2025. Accessed February 21, 2025. https://www.fda.gov/news-events/press-announcements/fda-approves-first-treatment-cerebrotendinous-xanthomatosis-rare-lipid-storage-disease.
Campbell P. Mirum Pharmaceuticals submits NDA for Chenodiol tablets in cerebrotendinous xanthomatosis. HCP Live. June 28, 2024. Accessed February 21, 2025. https://www.hcplive.com/view/mirum-pharmaceuticals-submits-nda-for-chenodiol-tablets-in-cerebrotendinous-xanthomatosis.
Carson BE, De Jesus O. Cerebrotendinous Xanthomatosis. [Updated 2023 Aug 23]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK564330/
