FDA Approves Ctexli for Cerebrotendinous Xanthomatosis

Mirum Pharmaceuticals has achieved a significant milestone with the U.S. Food and Drug Administration (FDA) granting approval for its drug Ctexli (chenodiol), designed to treat cerebrotendinous xanthomatosis (CTX) in adults. CTX is a rare lipid storage disorder, and Ctexli is the first medication to receive FDA approval for this specific condition. Notably, this approval underscores a pivotal advancement in treatment options for those suffering from this progressive and debilitating disease, which previously had no sanctioned therapeutic solutions.

The journey to FDA approval included a comprehensive evaluation of Ctexli's efficacy through a 24-week, placebo-controlled, randomized, double-blind crossover withdrawal study. Patients administered with Ctexli at a dosage of 250 mg three times daily demonstrated a significant reduction in plasma cholestanol and urine 23S-pentol levels. This outcome highlights Ctexli’s role in addressing deficiencies in bile acids, thereby reducing the deposition of abnormal cholesterol metabolites within the body.

Janet Maynard, director of the FDA's Center for Drug Evaluation and Research, Office of Rare Diseases, Pediatrics, Urologic and Reproductive Medicine, emphasized the importance of this development. She noted the FDA's commitment to advancing drug development for rare and very rare metabolic disorders like CTX. Maynard pointed out that CTX is a progressive multisystemic disorder that severely affects patients, and the newly approved treatment offers a secure and effective solution for those impacted.

However, the drug is accompanied by a cautionary note regarding liver toxicity, especially for individuals with pre-existing liver conditions or bile duct abnormalities, who may face an elevated risk of liver damage. As a precaution, liver function tests are advised before starting treatment, annually thereafter, and as clinically warranted. Patients experiencing symptoms such as stomach pain, nausea, or yellowing of the skin are advised to cease treatment and seek medical consultation.

Commonly observed side effects of Ctexli include diarrhea, abdominal pain, and upper respiratory tract infections. These side effects should be taken into consideration when evaluating the overall treatment regimen for patients.

CTX originates from a mutation in the cytochrome P450 family 27 subfamily A member 1 (CYP27A1) gene, leading to a deficiency in an enzyme essential for fat metabolism. This deficiency results in the abnormal accumulation of cholesterol metabolites across various tissues and organs, causing significant damage.

In addition to its recent FDA approval, Mirum Pharmaceuticals expanded its portfolio in July 2023 by acquiring bile acid product assets from Travere Therapeutics in a $445 million deal. This acquisition aligns with the company's strategic vision to enhance its offerings in the realm of bile acid-related treatments.

Overall, the approval of Ctexli marks a considerable leap forward for both Mirum Pharmaceuticals and patients with CTX, offering hope and a new therapeutic avenue for managing this rare and challenging disease.