The U.S. Food and Drug Administration (FDA) approved chenodiol (Ctexli, Mirum Pharmaceuticals Inc.) for the treatment of cerebrotendinous xanthomatosis (CTX) in adults.
Chenodiol is the first FDA-approved drug to treat CTX, a very rare lipid storage disease.
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 deposition of atypical cholesterol metabolites in various places in the body including the brain, liver, skin and tendons, leading to damage to those organs and tissues. 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 efficacy of chenodiol for the treatment of patients with CTX was evaluated in a double-blind, placebo controlled, randomized crossover withdrawal trial. The 24-week trial demonstrated that treatment with chenodiol, 250 milligrams (mg) three times per day, resulted in significant reduction in plasma cholestanol and urine 23S-pentol, compared to placebo treatment.
The prescribing information for chenodiol includes a warning for liver toxicity in all patients with increased risk for liver damage in patients with pre-existing liver disease or bile duct abnormalities. Patients should obtain liver blood tests before starting treatment, annually while on treatment and as clinically indicated. If signs of liver toxicity occur, patients are advised to see their doctor and discontinue chenodiol.
The most common side effects of chenodiol are diarrhea, headache, abdominal pain, constipation, hypertension, muscular weakness and upper respiratory tract infection.
The recommended dosage is 250mg taken orally three times a day.
The FDA granted chenodiol Priority Review, Fast Track and Orphan Drug designations for this application.
