Mirum Submits FDA Application for Chenodiol to Treat CTX

Mirum Pharmaceuticals, Inc., a biopharmaceutical company, announced the submission of a new drug application (NDA) for chenodiol aimed at treating cerebrotendinous xanthomatosis (CTX) in the United States. CTX is a rare genetic disorder affecting cholesterol metabolism, which can lead to serious health complications if untreated.

Characterized by a deficiency in the bile acid CDCA, CTX leads to the accumulation of harmful bile alcohols and cholestanol, causing symptoms like chronic diarrhea, juvenile cataracts, tendon xanthomas, and neurological issues. The condition is progressive and can result in irreversible damage.

The NDA is supported by positive results from the Phase 3 RESTORE study, which evaluated chenodiol in adult CTX patients. The study achieved its primary goal of significantly reducing bile alcohol levels (p<0.0001), with a 20-fold difference observed between the placebo and chenodiol groups during the double-blind withdrawal period. Additionally, the treatment improved serum cholestanol levels. Common side effects included mild to moderate diarrhea and headache, which were mostly considered unrelated to the treatment.

Mirum's CEO, Chris Peetz, expressed enthusiasm about the potential approval of chenodiol, which would be the first and only medication approved in the U.S. for CTX. This could lead to earlier diagnosis and management of the disease. Jean Pickford, Executive Director of the CTX Alliance, also highlighted the importance of timely diagnosis and treatment, reflecting optimism about the FDA approval and subsequent impact on patients' lives.

The Phase 3 RESTORE study was a randomized, placebo-controlled trial that focused on the safety and efficacy of chenodiol in CTX patients. The study involved multiple treatment and withdrawal periods, including an open-label pediatric group, and was conducted at various sites in the U.S. and Brazil. Participants received 250 mg of chenodiol tablets three times daily. The main goal was to measure changes in blood and urine biomarkers associated with CTX.

CTX is an inherited autosomal recessive disorder that prevents the body from properly metabolizing cholesterol, leading to a toxic buildup of substances such as cholestanol and bile alcohols. This buildup affects various body parts, causing symptoms like neonatal jaundice, chronic diarrhea, early-onset bilateral cataracts, tendon xanthomas, and progressive neurological decline. The variability in symptoms often results in delayed diagnosis.

Chenodiol, also known as chenodeoxycholic acid (CDCA), is a naturally occurring bile acid previously approved for treating gallbladder stones. Recently, the FDA granted it orphan drug designation for CTX. While not yet approved for CTX treatment, it has been recognized as medically necessary by the FDA.

Mirum Pharmaceuticals is dedicated to addressing rare pediatric and adult diseases, with a portfolio that includes three approved medications: LIVMARLI, CHOLBAM, and CHENODAL. LIVMARLI is used to treat cholestatic pruritus in Alagille syndrome and progressive familial intrahepatic cholestasis in children and adults. CHOLBAM is for bile acid synthesis disorders and peroxisomal disorders, while CHENODAL is recognized for treating CTX. The company's pipeline includes investigational treatments for rare liver diseases, including volixibat, which is under evaluation for conditions like primary sclerosing cholangitis and primary biliary cholangitis.

Mirum is committed to advancing treatments and improving the lives of individuals with rare diseases, continuing to develop and explore new therapeutic options.