Mirum Pharmaceuticals’ Ctexli (chenodiol) was approved last week for the treatment of cerebrotendinous xanthomatosis (CTX) in adults. Ctexli is the first FDA–approved drug to treat CTX, a very rare genetic lipid storage disease.
The drug was acquired two years ago when Mirum Pharmaceuticals paid $210 million to acquire Travere Therapeutics’ bile acid portfolio. The FDA granted Ctexli Priority Review, Fast Track, and Orphan Drug designations for this application. The drug was not developed with CTX in mind. In fact, it has been cleared for decades to treat radiolucent gallstones under the brand name Chenodal.
“Today’s approval provides a safe and effective treatment option for CTX,” 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 genetic metabolic disorder caused by a mutation in CYP27A1. This leads to a deficiency of the mitochondrial enzyme sterol 27-hydroxylase. The lack of this enzyme prevents cholesterol from being converted into a bile acid called chenodeoxycholic acid. It is estimated that 3 to 5 among 100,000 individuals have the disease.
Patients with this condition have accumulations of cholesterol, and a related compound called cholestanol, in their nerve cells and membranes potentially causing damage to the brain, spinal cord, tendons, lens of the eye, and arteries. This is 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 (substances that result from the breakdown of cholesterol) in various places in the body.
Ctexli 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 Ctexli for the treatment of patients with CTX was evaluated in a double-blind, placebo-controlled, randomized crossover withdrawal trial. The 24-week Phase III trial demonstrated that treatment with Ctexli, 250 mg three times per day, resulted in a significant reduction in plasma cholestanol and urine 23S-pentol (cholesterol metabolites that are markedly increased in CTX patients) compared to placebo treatment.
In the 2023 transaction, Mirium paid Travere $210 million upfront and pledged up to $235 million in potential milestones to pick up Chenodal (chenodiol) and Cholbam, the latter of which was approved in 2015 for patients with rare bile acid synthesis disorders.
The prescribing information for Ctexli includes a warning for liver toxicity in all patients with increased risk for liver damage in those 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.
