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Background Analysis: US HHS Advisory Committee to Review Newborn Screening Topics and Discuss the Nomination of Cerebrotendinous Xanthomatosis to the Recommended Screening Panel – NOV 1-2, 2018 (ACHDNC)


The US Department of Health and Human Services (HHS) has scheduled an Advisory Committee on Heritable Disorders in Newborns and Children (ACHDNC) meeting for Thursday to Friday, November 1-2, 2018. The committee will hear from experts in the field and discuss issues related to newborn screening information, education, training activities, and training resources. The committee also will hear presentations on the use of genomic sequencing in newborn screening as well as the clinical setting for both well and sick infants. In addition, the committee will discuss the nomination of cerebrotendinous xanthomatosis (CTX) to the Recommended Uniform Screening Panel (RUSP) and vote on whether to move the nomination forward to evidence review. Note that this vote is only the first step in the RUSP pathway, not a proposed addition of the condition to the RUSP.

Background - Recommended Uniform Screening Panel

Newborn screening involves the testing of every newborn for certain conditions, such as hearing loss and certain genetic, endocrine, and metabolic disorders that may not be apparent at birth. It is a state-based public health system that includes education, screening, diagnostic follow-up and treatment. More than 98% of newborns in the United States are screened annually.

In 2006, the American College of Medical Genetics (ACMG) and the Health Resources and Services Administration (HRSA) brought experts together to provide advice on the standardization of the list of disorders for newborn screening. They recommended a uniform screening panel of 29 core/primary conditions to be included in state newborn screening panels: 20 inborn errors of metabolism, three hemoglobinopathies, and six other conditions. This panel was endorsed by ACHDNC and designated by the Secretary of HHS as a national standard for newborn screening programs. It is now known as the Recommended Uniform Screening Panel (RUSP). Since 2006, other disorders have been added to the RUSP.

The RUSP is recommended by the Secretary of HHS for states to screen as part of their state universal newborn screening (NBS) programs. It is recommended that every newborn be screened for all disorders on the RUSP. In practice, most states screen for the majority of disorders on the RUSP, and some states also screen for additional disorders.

Nominations of additional conditions for inclusion in the uniform panel can come from individuals and organizations with expertise on the nominated condition. ACHDNC reviews the nominations, following a systematic, evidence-based protocol. The overarching criteria are: there is a potential benefit of routinely screening all newborn babies for the disorder; public health laboratories have the ability to perform the test for the disorder; and there is the availability of effective treatments for the disorder. The ACHDNC provides recommendations to the Secretary of HHS, who makes the final determination on additions of disorders to the RUSP.

Background - Cerebrotendinous Xanthomatosis

Disease Background

At the upcoming meeting, the committee will discuss the nomination of cerebrotendinous xanthomatosis (CTX) to the RUSP. CTX is an autosomal-recessive lipid storage orphan disease caused by mutations in the CYP27A1 gene. It is characterized by an ineffective breakdown of lipids that leads to an accumulation of fatty nodules called xanthomas in the body, most commonly in the brain (cerebro-) and in connective tissue (tendinous). By early adulthood, people with CTX often develop neurological problems that are caused by xanthoma accumulation in the brain, and tendon problems that are caused by xanthoma accumulation in tendons. Neurologic problems include seizures, movement disorders, impaired speech, peripheral neuropathy, dementia, hallucinations, and depression. Tendon issues include discomfort and decreased flexibility. Other disease characteristics include premature cataracts, chronic diarrhea, cholestasis and osteoporosis.

The National Organization for Rare Disorders (NORD) says CTX is diagnosed based on a thorough clinical evaluation, a detailed patient and family history, and a variety of specialized tests including genetic testing and biochemical tests on blood and urine.

The medical community believes CTX is significantly underdiagnosed.


There are no US-FDA approved treatments for CTX. In the US, CTX is typically treated off-label with drug products containing chenodeoxycholic acid (a.k.a. CDCA, chenodiol) and cholic acid.

Leadiant Biosciences, Inc. (formerly Sigma-Tau Pharmaceuticals) says they are conducting a phase 3 trial of chenodiol for the treatment of CTX. Tarius could not locate this trial in the ClinicalTrials.Gov database. In June 2017, the company gained EU regulatory approval of a “hybrid medicine” named “Chenodeoxycholic acid Leadiant” for the treatment of CTX. The EU calls it a “hybrid medicine” because the application leverages information about a reference medicine with the same active ingredient. In this case, “Chenodeoxycholic acid Leadiant” was shown to be similar to the reference drug Xenbilox (EU trade name), which is approved for the treatment of certain gallstones. At the time of the approval, the company said the CTX marketing application was supported by findings from two retrospective clinical studies carried out in CTX treatment centers in the Netherlands and in Italy.

A second company, Retrophin, Inc., says that they are taking necessary steps to have a CTX indication added to the US product labeling for Chenodal (chenodiol), which the company says is FDA-approved for the treatment of certain gallstones. In the clinicatrials.gov database, Tarius found only one observational study by the company pertaining to CTX. The database shows there is an ongoing study to evaluate disease prevalence in patients with early-onset idiopathic bilateral cataracts that is estimated to be completed by December 2018 (ClinicalTrials.Gov Identifier: NCT02638220).

What’s Next?

Tarius will send a Results Wire soon after the meeting. This report will include the voting outcomes, if applicable, and key outcomes of the discussion.

METADATA: Sponsor: none Drug Name: none Drug Class: none Indication: none

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