Mirum submits NDA to the FDA for chenodiol for the treatment of cerebrotendinous xanthomatosis (CTX)

CTX is a rare autosomal genetic progressive disorder of cholesterol metabolism that affects many parts of the body. In CTX, a deficiency of the bile 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. If not treated, patients with CTX can experience symptoms that disrupt their lives and can progress over time, including chronic diarrhea, juvenile bilateral cataracts, tendon xanthomas, and neurologic deterioration.

The submission of the NDA is based on the positive results of the Phase III RESTORE study  which evaluated chenodiol in adult patients with CTX. The study met its primary endpoint of reduction in bile alcohols with high statistical significance (p<0.0001). the difference observed between placebo and active chenodiol at the end of the randomized double-blind withdrawal period was 20-fold. the restore study also demonstrated that treatment with chenodiol significantly improved serum cholestanol. the most common adverse events were diarrhea and headache, the majority of which were mild or moderate and not considered to be treatment related.

“Following the landmark RESTORE data, we are excited about the potential to have an approved treatment option that may reduce the progressive symptoms associated with this rare disease,” said Chris Peetz, chief executive officer at Mirum. “If approved, chenodiol would be the first and only medication approved to treat patients with CTX, enabling earlier diagnosis and treatment of these life-altering symptoms.”

About the RESTORE Phase III Study: The Phase III RESTORE study was a randomized withdrawal, placebo-controlled clinical trial which evaluated the safety and efficacy of chenodiol in patients with cerebrotendinous xanthomatosis (CTX). Chenodiol is administered at 250 mg three times daily in tablet format. The objective of the RESTORE study is to understand how the body responds, as measured by change in blood and urine biomarkers associated with CTX, when treated with chenodiol. The study involved a screening period (4 weeks), four treatment periods (totaling 6 months), and a follow-up phone call (30 days after last dose was administered). The four treatment periods consisted of: an 8-week open-label chenodiol period, a 4-week randomized withdrawal period (placebo or chenodiol), a second 8-week open-label chenodiol period for all patients, and a second 4-week randomized withdrawal period (alternate treatment to first withdrawal period).The primary analysis assessed change at the end of each double-blind withdrawal period. The study also included an open-label pediatric treatment group where all patients received liquid chenodiol. The study was conducted at multiple sites in the United States and Brazil.