FDA Approves Ctexli for Treating Rare Lipid Storage Disease CTX

The US Food and Drug Administration (FDA) has given the green light to Mirum Pharmaceuticals’ Ctexli (chenodiol) as a treatment for adults suffering from cerebrotendinous xanthomatosis (CTX). This approval marks the first time a therapy has been sanctioned by the FDA for this rare lipid storage disorder. CTX impacts approximately 2,000 individuals across the United States and is characterized by a genetic deficiency in an enzyme necessary for fat breakdown. The resulting enzyme deficiency leads to the accumulation of unusual cholesterol metabolites in the brain and other regions of the body.

CTX presents with a range of symptoms including chronic diarrhea, frequent bone fractures, cataracts, dementia, seizures, and speech difficulties. Ctexli operates by supplementing inadequate levels of a specific bile acid, thereby diminishing the abnormal cholesterol deposits believed to cause the clinical symptoms of CTX.

The FDA’s endorsement of Ctexli was bolstered by favorable outcomes from the 24-week phase 3 RESTORE trial. In this study, administration of Ctexli at a dosage of 250mg three times daily led to a notable decrease in plasma cholestanol and urine 23S-pentol—cholesterol metabolites significantly elevated in CTX patients—compared to a placebo group.

Nonetheless, the prescribing information for Ctexli includes a caution regarding potential liver toxicity. Consequently, patients are advised to undergo liver function tests prior to initiating treatment and annually thereafter during the course of treatment.

Reflecting on the approval, Chris Peetz, the CEO of Mirum, expressed optimism, stating, “The FDA’s approval of Ctexli is tremendous as it unlocks an opportunity to better identify and treat adult patients with CTX in the US. Our hope is that patients are diagnosed sooner and have a chance to avoid some of the debilitating and lasting symptoms associated with CTX.”

Janet Maynard, director of the Office of Rare Diseases, Pediatrics, Urologic, and Reproductive Medicine within the FDA’s Center for Drug Evaluation and Research, also commented on the approval. She emphasized the FDA’s commitment to advancing drug development for rare diseases, including very rare metabolic conditions like CTX. She remarked, “CTX is a progressive multi-systemic disorder that significantly impacts patients and previously lacked approved treatments. This approval provides a safe and effective treatment option for CTX.”

This landmark decision symbolizes a pivotal advancement for individuals affected by CTX, offering them newfound hope for managing the disease that was previously without approved therapeutic options. The introduction of Ctexli provides a treatment pathway that targets the underlying metabolic abnormalities characteristic of CTX, potentially altering the progression of the disease and improving the quality of life for those afflicted.