FDA approves Ctexli (chenodiol) tablets, a bile acid, for the treatment of adults with cerebrotendinous xanthomatosis – Mirum Pharma

Mirum Pharmaceuticals, Inc. announced that the FDA has approved Ctexli (chenodiol) tablets, a bile acid, for the treatment of adults with cerebrotendinous xanthomatosis (CTX). Ctexli  is the first and only treatment approved for this rare, progressive and debilitating disease.

The approval is based on data from the Phase III RESTORE study evaluating the safety and efficacy of Ctexli in adult patients with CTX by measurement of urine bile alcohols and other secondary measures. The primary endpoint of reduction in bile alcohols (urine 23S-pentol) was highly statistically significant (p<0.0001). At the end of the randomized double-blind withdrawal period, there was a 20-fold difference between placebo and Ctexli treated patients in urine 23S-pentol levels.

In CTX, a deficiency of the bile acid chenodeoxycholic acid (CDCA) leads to a buildup of bile alcohols which precedes a toxic accumulation of cholestanol. Cholestanol is the key driver of symptomatic burden and disease progression, including irreversible neurologic dysfunction. Results from the RESTORE study demonstrated that treatment with CtexliI not only improved urine bile alcohol levels but also serum cholestanol levels. Additionally, a greater proportion of patients receiving placebo required blinded rescue therapy, demonstrating the robustness of the effect.

CTX is a genetic disorder caused by a mutation in the CYP27A1 gene that results in a deficiency of the enzyme that allows the body to break down fats including cholesterol. A few thousand people are estimated to be living with CTX in the U.S., but many are thought to be undiagnosed. The Mirum Pharma medicine, which will be called Ctexli, has been used for many years in the U.S. under the Chenodal trade name to treat radiolucent gallstones, but according to the company has been widely used off-label to treat CTX.