FDA clears first therapy for rare disease CTX from Mirum

Mirum Pharma's Ctexli has become the first FDA-approved therapy for cerebrotendinous xanthomatosis (CTX), an ultra-rare form of lipid storage disease.

Ctexli (chenodiol) has been cleared to treat adults with CTX, a genetic disorder caused by a mutation in the CYP27A1 gene, which results in a deficiency of the enzyme that allows the body to break down fats including cholesterol. As a consequence, aberrant cholesterol metabolites accumulate in tissues like the brain, liver, skin, and tendons, causing damage.

Symptoms of CTX are highly variable, but include chronic diarrhoea, liver disease, fatty tumours in the joints, cataracts, seizures, and cognitive impairment. It is estimated that a few thousand people are living with CTX in the US, but many are thought to be undiagnosed.

The clinical trial that underpinned the approval of Ctexli showed that. at a dose of 250mg three times a day, there was a significant decrease in toxic cholesterol metabolites including cholestanol in the blood and 23S-pentol in urine at 24 weeks compared to placebo.

Ctexli has, however, been approved with a warning that it can lead to liver toxicity, and patients will have to undergo liver blood testing before they start treatment, as well as once a year while they are taking the drug.

The drug is based on chenodeoxycholic acid (CDCA), a naturally occurring bile acid, which has been approved in Europe to treat CTX for several years. In the US it has been used for many years under the Chenodal trade name to treat radiolucent gallstones, but according to Mirum it has been widely used off-label to treat CTX.

Combined sales of Chenodal and another bile acid therapy, Cholbam (cholic acid), reached around $123 million last year and analysts reckon Ctexli could add upwards of $150 million to that total. Overall, the company had revenues of $336 million last year and has forecast that will rise to between $420 million to $435 million this year. It has not yet revealed its launch or pricing plans for Ctexli.

"The FDA is dedicated to supporting new drug development for rare diseases including very rare metabolic diseases," said Janet Maynard, who is director of the Office of Rare Diseases, Paediatrics, Urologic and Reproductive Medicine at the FDA.

"CTX is a progressive multisystemic disorder that significantly impacts patients and previously lacked approved treatments," she added. "Today's approval provides a safe and effective treatment option."

Mirum acquired rights to Ctexli through its takeover of Travere Therapeutics' bile acid business for $210 million upfront in 2023, with $235 million in potential milestones.