The U.S. Food and Drug Administration has marked a significant milestone in rare disease treatment by approving chenodiol tablets (Ctexli) for adults with cerebrotendinous xanthomatosis (CTX), providing the first authorized therapy for this rare genetic lipid storage disorder.
The approval, announced on February 21, 2025, was granted to Mirum Pharmaceuticals following compelling results from their Phase 3 RESTORE clinical trial. The study demonstrated the drug's ability to significantly reduce bile alcohols in CTX patients, achieving a remarkable 20-fold difference compared to placebo.
"CTX is a progressive multisystemic disorder that significantly impacts patients and previously lacked approved treatments," stated Dr. Janet Maynard, director of the Office of Rare Diseases, Pediatrics, Urologic, and Reproductive Medicine at the FDA's Center for Drug Evaluation and Research (CDER).
Understanding CTX and Treatment Mechanism
CTX stems from a mutation in the CYP27A1 gene, which impairs the body's ability to break down fats properly. The condition is characterized by reduced production of bile acid CDCA in the liver, leading to toxic accumulations of cholestanol throughout the body, particularly affecting the brain, liver, skin, and tendons. If left untreated, these deposits can cause severe organ damage and irreversible neurological dysfunction.
Chenodiol works by replacing deficient bile acids, thereby reducing the abnormal deposits of cholesterol metabolites responsible for CTX's clinical manifestations. The treatment is administered as 250 mg tablets three times daily.
Clinical Trial Results and Safety Profile
The RESTORE trial, designed as a double-blind, placebo-controlled, randomized crossover withdrawal study, evaluated chenodiol's safety and efficacy over multiple treatment periods spanning six months. The study achieved its primary endpoint with high statistical significance (P<0.0001), demonstrating substantial reductions in bile alcohols and improvements in serum cholestanol levels.
However, the FDA has included important safety considerations in the drug's prescribing information. Patients must undergo liver blood tests before starting treatment and annually thereafter, with additional monitoring as clinically indicated. The most frequently reported side effects include:
- Diarrhea
- Headache
- Abdominal pain
- Constipation
- Hypertension
- Muscular weakness
- Upper respiratory tract infection
Regulatory Recognition and Impact
The drug's significance in addressing this rare disease is reflected in its receipt of multiple FDA designations, including Priority Review, Fast Track, and Orphan Drug status. These designations helped expedite the development and review process for this crucial therapy.
"The FDA is dedicated to supporting new drug development for rare diseases, including very rare metabolic diseases like CTX," emphasized Dr. Maynard, highlighting the agency's commitment to addressing unmet medical needs in rare disease communities.
