Mirum Pharmaceuticals’ Ctexli (chenodiol) has become the first drug to be approved by the US Food and Drug Administration (FDA) as a treatment for cerebrotendinous xanthomatosis (CTX), a rare metabolic disorder.
Chenodiol was first approved under the brand name Chenix in 1983 and reapproved as Chenodal in 2009 for the treatment of gallstones. The San Francisco-based company added Ctexli to its portfolio as part of the $445 million deal with Travere Therapeutics’ bile acid portfolio. Mirum paid $210 million upfront along with a promise of up to $235 million in potential sales-based milestone payments.
The Travere acquisition also included Cholbam (cholic acid) indicated for the treatment of bile acid synthesis disorders due to single enzyme deficiencies and adjunctive treatment of peroxisomal disorders in patients who show signs or symptoms of liver disease.
Ctexli trial data
CTX is a genetic metabolic disorder that occurs due to a gene mutation that causes a deficiency of the enzyme the body uses to break down fats. Patients with CTX have reduced bile acid production and are unable to break down cholesterol. This leads to buildups of atypical cholesterol metabolites in various body parts including the brain, liver, skin, and tendons.
Ctexli replaces the deficient levels of one of the bile acids, thereby reducing the abnormal deposits of cholesterol metabolites thought to be responsible for clinical abnormalities in CTX. The FDA approval was based on the positive data from a placebo-controlled, crossover Phase III RESTORE study (NCT04270682).
The trial enrolled 13 adult participants with CTX. The study met its primary endpoint of achieving a ’20-fold’ reduction in bile alcohols (urine 23S-pentol) with Ctexli, compared to a placebo at the end of the randomized double-blind withdrawal period. The drug also achieved a significant reduction in plasma cholestanol, an intermediate in the synthesis of bile acids from cholesterol.
Ctexli also carries a warning for liver toxicity in all patients with an increased risk for liver damage in patients with pre-existing liver disease or bile duct abnormalities. The FDA advises conducting “liver blood tests before starting treatment, annually while on treatment and as clinically indicated”.
Common side effects of Ctexli include diarrhea, headache, abdominal pain, constipation, hypertension, muscular weakness and upper respiratory tract infection.
Another product in Mirum’s portfolio is volixibat. The company is evaluating the therapy as a treatment for primary sclerosing cholangitis, and primary biliary cholangitis in two Phase IIb VISTAS (NCT04663308) and VANTAGE (NCT05050136) trials respectively.
