On February 21, 2025, the U.S. Food and Drug Administration (FDA) approved CTEXLI™ (chenodiol) oral tablets for the treatment of cerebrotendinous xanthomatosis (CTX), a rare genetic metabolic disorder, in adults. It is the first FDA-approved medicine for CTX. This medication is manufactured by Mirum Pharmaceuticals, Inc., California, United States. The recommended dosage is 250 mg taken orally three times a day.
CTX is a progressive and multisystemic lipid storage disorder with no previous approved treatments. This drug provides patients with CTX with safe and effective treatment,” said Janet Maynard, M.D., M.H.S., director of the Office of Rare Diseases, Pediatrics, Urologic, and Reproductive Medicine, in the FDA’s Center for Drug Evaluation and Research.
CTX occurs due to CYP27A1 gene mutations which lead to enzyme deficiency that disrupts the process of cholesterol breakdown. This results in the accumulation of abnormal cholesterol metabolites in the skin, liver, tendons, and brain. These deposits ultimately cause organ or tissue damage. Ctexli replaces the deficient bile acids along with reducing these metabolite accumulations and their harmful effect.
This approval is based on a randomized, double-blind, placebo-controlled, 2-period with 2-treatment crossover withdrawal clinical trial (NCT 04270682). This clinical study assessed the safety and effectiveness of Ctexli in patients with CTX. A total of 13 patients (median age = 42 (16-55) years, 62% male, 39% female, 62% White, 54% non-Hispanic) were randomized and treated either with Ctexli or placebo orally 3 times per day for 4 weeks in 2 double-blinded periods. Between two double-blind withdrawal periods, patients received Ctexli 250 mg 3 times daily for 8 weeks during the run-in phase and 8 weeks during the open-label period. The total treatment duration for the study was 24 weeks. Plasma cholestanol and urine 23S-pentol were measured at different time intervals.
At day 29, the estimated mean change from baseline in plasma cholestanol was found to be -2.3 µg/mL for the Ctexli group and -2.3 µg/mL in the placebo group with an estimated treatment difference of -8.5 µg/mL (95% confidence interval [CI]: -13.2, -3.9). Additionally, for urine 23S-pentol, the estimated mean change from baseline was 185 ng/mL in the Ctexli group and 29506 ng/mL in the placebo group with an estimated treatment difference of -29321 ng/mL (95% CI: -45701, -12941). Overall plasma cholestanol and urine 23S-pentol levels were reduced in the treatment group compared to placebo subjects.
The warning for hepatotoxicity should be included in the prescribing information of Ctexli. This toxicity is noted in patients with an increased risk of liver damage and patients with a history of liver disease and bile duct abnormalities.
Patients were strongly recommended to take liver function tests before and during the treatment and when clinically necessary. If any symptoms of hepatotoxicity like nausea, stomach pain, bruising, itching, dark urine, jaundice, or fatigue were observed, patients should stop the Ctexli treatment and consult their doctor immediately.
The common adverse events (incidence >14%) of Ctexli include headache, hypertension, diarrhea, constipation, upper respiratory tract infections, muscular weakness, and abdominal pain.
Reference:
- U.S. Food & Drug Administration. FDA Approves First Treatment for Cerebrotendinous Xanthomatosis, a Rare Lipid Storage Disease. Published February 21, 2025. Accessed February 24, 2025. https://www.fda.gov/news-events/press-announcements/fda-approves-first-treatment-cerebrotendinous-xanthomatosis-rare-lipid-storage-disease
- FDA access data. Highlights of Prescribing Information-Ctexli. Revised 2/2025. https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/219488s000lbl.pdf
