FDA Approves First Treatment for a Rare Lipid Storage Disease

On February 21, 2025, the Food and Drug Administration of the United States (FDA) approved Ctexli (chenodiol) for CTX therapy in adults, a decision that is a huge leap forward for patients with this rare lipid storage disease. Ctexli is the first and only medication for cerebrotendinous xanthomatosis and brings promise to the afflicted by this progressive and life-changing metabolic disorder.

A Breakthrough for a Rare Disease:

A CTX is a genetic disorder and is classified as a disorder of metabolism as a result of a mutation in the genes associated with the CYP27A1, leading to fat metabolic failure. This deficiency causes a reduction of the bile acid, which makes the body tissues produce and retain excessive amounts of cholesterol along with its excess products. The brain, liver, skin, tendons, and other parts of the body produce more than the required amounts, and this surpasses the limit of what the body can put to healthy use. This results in chronic neuro dysfunction, failure of the development of an individual, and failure of multiple organs, thus declining the standard of life.

Until now, there was no FDA-approved therapy for CTX, leaving patients with limited options to manage their symptoms. The approval of Ctexli provides a targeted bile acid replacement therapy that helps reduce the abnormal cholesterol deposits, addressing the underlying cause of the disease rather than just the symptoms.

FDA’s Commitment to Rare Disease Research:

The FDA is dedicated to supporting new drug development for rare diseases, including very rare metabolic disorders like cerebrotendinous xanthomatosis,” said Dr. Janet Maynard, M.D., M.H.S., director of the Office of Rare Diseases, Pediatrics, Urologic, and Reproductive Medicine at the FDA’s Center for Drug Evaluation and Research.
She further said, ”CTX is a progressive multisystemic disorder which is storrowing to patients and has not been treated adequately for a long time. This approval means that patients suffering from CTX can safely and efficiently be treated.”

Clinical Trial Results Show Efficacy of Ctexli:

Ctexli was demonstrated to be effective in the 24-week interval double blind placebo controlled randomized withdrawal trial evaluating its effectiveness in the reduction of the cholestrol metabolites that are exceptionally high in CTX patients. The patients who were treated with Ctexli were evaluated for the relief of the CTX symptoms via reduction of the plasma cholestanol and urine 23S-pentol levels.

Those patients who were given 250mg of Ctexli thrice daily showed marked reduction in plasma cholestanol and urine 23S-pentol levels in comparison to those who were given placebo. This proves that Ctexli is efficacious in reducing the abnormal deposition of cholestrol, which leads to clinical complications of CTX.

Safety Precautions and Possible Side Effects:

Ctexli therapy for CTX is efficacious, but patients must be warned of possible hepatotoxicity. The prescribing information includes a warning for liver toxicity, especially in those with previous liver disease and bile duct lesions.
Patients on Ctexli must have pre-treatment liver blood tests conducted, during treatment, and at any clinically appropriate time. Signs of liver toxicity include:

• stomach pain
• nausea
• fatigue
• dark urine
• bruising
• yellowing of the skin and
• eyes
• itching

Any patient who has these symptoms must see their doctor at once and stop using the medication.

The most common side effects reported in clinical trials include:

• diarrhea
• headache
• abdominal pain
• constipation
• hypertension
• muscular weakness
• upper respiratory tract infections

Dosage of Ctexli is 250 mg per day administered orally in three divided doses.

Regulatory Milestones and Priority Designations:

Due to the urgent need for CTX treatment, the FDA has awarded Ctexli Priority Review, expediting its evaluation based on significant medical necessity, and Fast Track Designation, accelerating its development to ensure quicker public availability.