The U.S. Food and Drug Administration (FDA) has approved Mirum Pharmaceuticals’ 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 3 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 CTEXLI 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.
“The FDA’s approval of CTEXLI is tremendous as it unlocks an opportunity to better identify and treat adult patients with CTX in the United States. Our hope is that patients are diagnosed sooner and have a chance to avoid some of the debilitating and lasting symptoms associated with CTX,” said Chris Peetz, chief executive officer at Mirum. “We are grateful to the clinicians, patients, advocates, and families who participated in the research that led to this approval and who have continued to provide support to this community.”
“Cerebrotendinous xanthomatosis (CTX) is a rare disease that can present with early cataracts, tendon lipid deposits, and significant neurologic disease, and the latter may be prevented with earlier diagnosis and treatment,” said Ernst J. Schaefer, MD, professor of medicine at Tufts University School of Medicine in Boston and chief medical officer and laboratory director at Boston Heart Diagnostics. “Treatment with CTEXLI has been shown to lower bile alcohols and cholestanol levels, reducing the progressive symptoms associated with CTX.”
“CTX is a devastating disease that is often diagnosed in early adulthood with progressive symptoms that can have a significant impact on a person’s quality of life,” said Jean Pickford, executive director, CTX Alliance. “We are thrilled that CTEXLI is now approved and hope that patients with this disease are diagnosed earlier and can avoid potentially irremediable disease progression and many of the debilitating symptoms associated with CTX.”
