Effective Date

Date of Origin 

10-01-2025            

10-01-2025

Ctexli™

(chenodiol)

Tablet

Treatment of cerebrotendinous xanthomatosis (CTX) in adults

1

Cerebrotendinous xanthomatosis (CTX)

Cerebrotendinous xanthomatosis (CTX) is a rare autosomal recessive genetic disorder caused by an abnormality in the CYP27A1 gene, resulting in a deficiency of the mitochondrial enzyme sterol 27-hydroxylase. The lack of this enzyme prevents cholesterol from being converted into a bile acid called chenodeoxycholic acid. Deposits of cholesterol and a related compound called cholestanol accumulate in the nerve cells and membranes potentially causing damage to the brain, spinal cord, tendons, lens of the eye and arteries.(2) Affected individuals may experience infantile-onset diarrhea, childhood-onset cataract, adolescent- to young adult-onset tendon xanthomas (present in areas of the body such as the lungs, tendons, bone or central nervous system), and adult-onset progressive neurologic dysfunction (dementia, psychiatric disturbances, pyramidal and/or cerebellar signs, dystonia, atypical parkinsonism, peripheral neuropathy, and seizures).(4) The specific symptoms and progression of this disorder can vary greatly from one individual to another, even for twins with the same abnormality in the CYP27A1 gene.(2)

CTX is diagnosed based on a thorough clinical evaluation, a detailed patient and family history, identification of characteristic clinical findings, and specialized tests including genetic testing and biochemical tests on blood and urine. Genetic testing can confirm a diagnosis of CTX by detecting disease-causing (pathogenic) variants in the CYP27A1 gene known to cause the disorder. Due to the lack of enzyme sterol 27-hydrozylase, the cholestanol concentration in plasma or serum is high (greater than or equal to 5 to 10 times the upper limit of normal (ULN), while the plasma cholesterol concentration is normal to low. In addition, the concentration of bile acid pathway intermediates is elevated, and the concentration of bile alcohols in plasma, bile and urine is increased. Bile alcohols are formed in an alternative pathway present in CTX that generates some cholic acid. Overall, there is little or no formation of chenodeoxycholic acid.(2,4)

Treatment with chenodeoxycholic acid normalizes the production of cholestanol.(2) Endogenous chenodiol (chenodeoxycholic acid) is a primary bile acid, synthesized from cholesterol in the liver. In CTX, the major bile acid synthesis pathways are disrupted due to partial or total deficiency in sterol 27-hydroxylase encoded by the CYP27A1 gene. Ctexli may act to replace deficient levels of the endogenous bile acid chenodeoxycholic acid in patients with CTX. Increased chenodiol levels in the enterohepatic bile acid pool restore the activation of farnesoid X receptor (FXR) and downregulate CYP7A1 leading to suppression and reduction of atypical bile acids and bile alcohols including cholestanol and 23S-pentol.(1)

The efficacy of treatment with chenodeoxycholic acid can be monitored using biochemical testing to confirm a decrease in blood cholestanol. Treatment can prevent symptoms in asymptomatic individuals and stop the progression of disease symptoms in affected individuals. After significant disease progression, treatment does not readily reverse the neurological deficits that have already occurred. It may be effective to supplement with an HMG-CoA reductase inhibitor in conjunction with chenodeoxycholic acid. There are concerns that treatment with HMG-CoA reductase inhibitors could boost the activity of receptors for low-density lipoprotein (LDL) cholesterol, thereby increasing cholesterol uptake and potentially worsening CTX. HMG-CoA reductase inhibitors can also cause muscle damage.(2)

In 2009, the U.S. Food and Drug Administration (FDA) re-approved an artificially made (synthetic) form of chenodeoxycholic acid known as Chenodal as a treatment for gallstones. This drug is also used as a first-line therapy to treat individuals with CTX. In 2025, the FDA approved Ctexil (chenodiol) to treat adults with CTX. Cholic acid, another bile acid, has also been used to treat young children with CTX. Although chenodeoxycholic acid is considered as a first-line therapy to treat CTX, cholic acid lacks the potential hepatotoxicity sometimes associated with chenodeoxycholic acid.(2) However, a CTX panel of experts could not reach a consensus on the value of cholic acid therapy alone.(3)

Efficacy

Ctexli (chenodiol) has been associated with hepatotoxicity. In Trial 1, one Ctexli-treated patient (7%) had increased ALT levels > 3 times ULN, which led to treatment interruption. Patients with pre-existing liver disease or bile duct abnormalities may be at higher risk for hepatotoxicity during treatment with Ctexli. Published reports suggest patients who are poor sulfators of lithocholic acid are more likely to develop chenodiol-induced serum aminotransferase elevations. Baseline liver transaminase (ALT, AST) and total bilirubin levels should be obtained in all patients prior to treatment initiation with Ctexli. If liver transaminase levels are elevated > 3 times ULN or total bilirubin level is >2 times ULN, interrupt treatment with Ctexli until the levels have returned to baseline values. Monitor liver transaminase and total bilirubin levels yearly and as clinically indicated. For persistent or recurrent liver test abnormalities, consider discontinuing Ctexli.

The efficacy of Ctexli for the treatment of patients with CTX was evaluated in Trial 1, which was a randomized, double-blind, placebo controlled, 2-period with 2-treatment crossover trial in patients greater than or equal to 16 years of age (NCT 04270682). In Trial 1, 14 patients were enrolled and 13 patients were randomized and treated in a crossover withdrawal design to receive either Ctexli 250 mg or placebo orally three times daily for 4 weeks during 2 double-blind treatment periods. The study also included treatment with Ctexli 250 mg three times daily during an 8 week run-in period and an 8-week open label period in between the 2 doubleblind withdrawal periods. The total duration of study treatment was 24 weeks. Of the 13 randomized patients, 62% were male and 39% were female. The baseline median age was 42 years (16-55) and median age at diagnosis was 35 years (15-55). Ctexli is not approved for use in pediatric patients.

Plasma cholestanol and urine 23S-pentol were assessed at multiple time points. For plasma cholestanol, the estimated mean change from baseline at day 29 was -2.3 µg/mL when patients continued Ctexli treatment and 6.2 µg/mL when patients received placebo. For urine 23S-pentol, the estimated mean change from baseline at day 29 was 185 ng/mL when patients continued Ctexli treatment and 29506 ng/mL when patients received placebo. The estimated treatment difference was -29321 ng/mL.(1)

Safety

Ctexli has no FDA labeled contraindications for use.

1

Ctexli prescribing information. Mirum Pharmaceuticals, Inc. February 2025.

2

NORD. Cerebrotendinous Xanthomatosis. Last updated: 2/24/2025. Published 2020. 

3

Stelten BML, Dotti MT, Verrips A, et al. Expert opinion on diagnosing, treating and managing patients with cerebrotendinous xanthomatosis (CTX): a modified Delphi study. Orphanet Journal of Rare Diseases. 2021;16(1). doi:10.1186/s13023-021-01980-5

4

Federico A, Gallus GN. Cerebrotendinous xanthomatosis. GeneReviews - NCBI Bookshelf. Published November 14, 2024. https://www.ncbi.nlm.nih.gov/books/NBK1409/

Ctexli

chenodiol tab

250 MG

M ; N ; O ; Y

N

Ctexli

chenodiol tab

250 MG

90

Tablets

30

DAYS

79378031090

Ctexli

chenodiol tab

250 MG

Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx ; SourceRx-Performance

Ctexli

chenodiol tab

250 MG

Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx ; SourceRx-Performance

PA

Initial Evaluation

Target Agent(s) will be approved when ALL of the following are met:

1. ONE of the following:
   1. The requested agent is eligible for continuation of therapy AND ONE of the following:

1. 1. 1. The patient has been treated with the requested agent (starting on samples is not approvable) within the past 90 days OR
      2. The prescriber states the patient has been treated with the requested agent (starting on samples is not approvable) within the past 90 days AND is at risk if therapy is changed OR
   2. BOTH of the following:
      1. ONE of the following:
         1. The patient has a diagnosis of cerebrotendinous xanthomatosis (CTX) as confirmed by ONE of the following:
            1. Genetic testing confirming variants in the CYP27A1 gene OR
            2. ALL of the following:
               1. Elevated plasma cholestanol greater than or equal to 5 to 10 times ULN (upper limit of normal) AND
               2. Urine positive for bile alcohols AND
               3. Clinical findings consistent for CTX [e.g., xanthomas (present in lungs, tendons, bone or central nervous system), infantile-onset diarrhea, childhood-onset cataract(s), adult-onset progressive neurologic dysfunction (dementia, psychiatric disturbances, pyramidal and/or cerebellar signs, dystonia, atypical parkinsonism, peripheral neuropathy, and seizures] OR
         2. The patient has another FDA labeled indication for the requested agent and route of administration AND
      2. If the patient has an FDA labeled indication, then ONE of the following:
         1. The patient’s age is within FDA labeling for the requested indication for the requested agent OR
         2. There is support for using the requested agent for the patient’s age for the requested indication AND
2. The patient has had a baseline liver transaminase (alanine aminotransferase [ALT] and aspartate aminotransferase [AST]) and total bilirubin level prior to initiating the requested agent AND
3. The prescriber is a specialist in the area of the patient’s diagnosis (e.g., gastroenterologist, geneticist, hepatologist, endocrinologist, neurologist), or the prescriber has consulted with a specialist in the area of the patient’s diagnosis AND
4. The patient does NOT have any FDA labeled contraindications to the requested agent

Length of Approval: 12 months

NOTE: If Quantity Limit applies, please refer to Quantity Limit Criteria.

Renewal Evaluation

Target Agent(s) will be approved when ALL of the following are met:

1. The patient has been previously approved for the requested agent through the plan’s Prior Authorization process [Note: patients not previously approved for the requested agent will require initial evaluation review] AND
2. The patient has had clinical benefit with the requested agent AND
3. The patient is monitored for changes in liver transaminase (alanine aminotransferase [ALT] and aspartate aminotransferase [AST]) and total bilirubin level AND BOTH of the following:
   1. The patient has liver transaminase levels less than 3 times the upper limit of normal (ULN) AND
   2. The patient has a total bilirubin level less than 2 times the ULN AND
4. The prescriber is a specialist in the area of the patient’s diagnosis (e.g., gastroenterologist, geneticist, hepatologist, endocrinologist, neurologist), or the prescriber has consulted with a specialist in the area of the patient’s diagnosis AND
5. The patient does NOT have any FDA labeled contraindications to the requested agent

Length of Approval: 12 months

NOTE: If Quantity Limit applies, please refer to Quantity Limit Criteria.

Universal QL

Quantity limit for the Target Agent(s) will be approved when ONE of the following is met:

1. The requested quantity (dose) does NOT exceed the program quantity limit OR
2. The requested quantity (dose) exceeds the program quantity limit AND ONE of the following:
   1. BOTH of the following:
      1. The requested agent does NOT have a maximum FDA labeled dose for the requested indication AND
      2. There is support for therapy with a higher dose for the requested indication OR
   2. BOTH of the following:
      1. The requested quantity (dose) does NOT exceed the maximum FDA labeled dose for the requested indication AND
      2. There is support for why the requested quantity (dose) cannot be achieved with a lower quantity of a higher strength that does NOT exceed the program quantity limit OR
   3. BOTH of the following:
      1. The requested quantity (dose) exceeds the maximum FDA labeled dose for the requested indication AND
      2. There is support for therapy with a higher dose for the requested indication

Length of Approval:  up to 12 months