FDA Approves First Treatment for Rare Lipid Storage Disease Cerebrotendinous Xanthomatosis

FDA has granted approval to California-based Mirum Pharmaceuticals for Ctexli (chenodiol) for treatment of the genetic metabolic disorder cerebrotendinous xanthomatosis (CTX) in adults. FDA announced the decision in a press release on Feb. 21, 2025 (1).

Ctexli becomes the first FDA-approved drug to treat CTX, which is a rare lipid storage disease that is caused by a mutation in the CYP27A1 gene (1). This results in a deficiency of an enzyme that is important, FDA said, insofar as the body’s ability to break down cholesterol in a normal way, exacerbated by the gene mutation causing reduced bile production in the liver. When that happens, atypical cholesterol metabolites are deposited and cause damage in places in the body such as the brain, liver, skin, and tendons.

“FDA is dedicated to supporting new drug development for rare diseases including very rare metabolic diseases like cerebrotendinous xanthomatosis,” said Janet Maynard, MD, director of the Office of Rare Diseases, Pediatrics, Urologic and Reproductive Medicine, in FDA’s Center for Drug Evaluation and Research, in the press release (1). "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.”

In an interview with Pharmaceutical Technology® around DCAT Week 2023, Roger Viney, chief commercial officer at ICE Pharma, spoke about the history of bile acid therapeutics up to the current day (2).

“The last 20 years have seen a huge growth of medicinal research in bile acids. As recently as 1999, the scientific community recognized that bile acids are metabolic regulators—and this opened a whole new area of research into bile acid-based medicines ... [including] cholic acid, deoxycholic acid, chenodeoxycholic acid, their salts and taurine and glycine conjugates, which find diverse uses from nutraceuticals to excipients and APIs,” Viney said at the time.

Another treatment for CTX, Sigma-Tau Pharmaceuticals’ chenodeoxycholic acid candidate, was given a positive opinion by the European Medicines Agency’s Committee for Medicinal Products for Human Use at its September 2016 meeting (3).

But in 2021, after Sigma-Tau had rebranded as Leadiant Biosciences, the Netherlands Authority for Consumers and Markets levied a fine of €19.5 million (US$23 million as of 2021) against Leadiant for excessive pricing of its CTX drug—a price the company had raised by 1800%—as part of a regulatory examination of infringements of the Competition Act of 1998 (4).

Meanwhile, two other drugs designed to treat another rare disease affecting the liver, primary biliary cholangitis (PBC), are moving forward early in 2025. Cour Pharmaceuticals received an orphan drug designation from FDA in January 2025 for its CNP-104, which is a biodegradable nanoparticle that encapsulates the E2 component of the mitochondrial pyruvate dehydrogenase complex, a key autoantigen in PBC (5). And in February 2025, Gilead Sciences was granted conditional marketing authorization by the European Commission for seladelpar, an oral, peroxisome proliferator-activated receptor-delta agonist (6).

Concerning the approval of Ctexli, FDA said in its press release that the recommended dosage for chenodiol is 250 milligrams, taken orally three times a day (1). Prescribing information includes a warning for liver toxicity in all patients, and increased risk of liver damage in patients with pre-existing liver disease or bile duct abnormalities.

References

1. FDA. FDA Approves First Treatment for Cerebrotendinous Xanthomatosis, a Rare Lipid Storage Disease. Press Release. Feb. 21, 2025.
2. Playter, G. Exploring Bile Acid Therapeutics with Roger Viney (DCAT Week). PharmTech.com, May 1, 2023.
3. Pharmaceutical Technology Editors. EMA Recommends Approval of 10 Drugs. PharmTech.com, Sept. 16, 2016 (accessed Feb. 24, 2025).
4. Thomas, F. Drug Pricing Scrutiny Increases in Europe. Pharmaceutical Technology Europe 2021, 33 (8), 6.
5. Cour Pharmaceuticals. Cour Pharmaceuticals Secures FDA Orphan Drug Designation for CNP-104 in Primary Biliary Cholangitis. Press Release. Jan. 8, 2025.
6. Gilead Sciences. Gilead’s Seladelpar Granted Conditional European Marketing Authorization for the Treatment of Primary Biliary Cholangitis. Press Release. Feb. 20, 2025.