New Drug RelyvrioTM
(sodium phenylbutyrate and taurursodiol)
By: Benita Mukenge, PharmD Candidate 2023
Classification: Histone Deacetylase Inhibitor; Hydrophilic Bile Acid FDA Approval: September 29, 2022
Indication1: Treatment of amyotrophic lateral sclerosis (ALS) in adult patients Contraindications: None
Pharmacology1,2: The exact mechanism of action is unknown; however, the combination of sodium phenylbutyrate and taurursodiol minimizes physical function decline by slowing down neuronal death.
Pharmacokinetics Absorption: Sodium phenylbutyrate is rapidly absorbed; however, co-administration with high-fat 1,2
meals diminishes absorption and exposure (Cmax by 76% and AUC by 54%). The presence of food had no effect on taurursodiol, although overall exposure after a high-fat meal increased AUC by 39%. Distribution: Both taurursodiol and sodium phenylbutyrate are highly protein bound (98% and 82%, respectively).
Metabolism: Major metabolites: phenylacetate (sodium phenylbutyrate); ursodiol and glycol-ursodiol (taurursodiol). Elimination: Approximately 80100% of phenylacetylglutamine is excreted through the urine within 24 hours. Clinical Efficacy3,4,5: The Trial of Sodium Phenylbutyrate-Taurursodiol for Amyotrophic Lateral Sclerosis (CENTAUR) evaluated sodium phenylbutyrate and Page 28
taurursodiol’s effect on prolonging the life of patients with amyotrophic lateral sclerosis (ALS), which also goes by the term Lou Gehrig’s disease, by slowing down functional decline. The multicenter, randomized, double-blind trial enrolled 137 individuals with ALS who had an onset of symptoms within the previous 18 months. Eligible participants were recruited from 25 centers of the Northeast Amyotrophic Lateral Sclerosis Consortium (NEALS) in the United States from June 2017 through September 2019. The study included adults 18-80 years of age with sporadic or familial ALS diagnoses. A positive ALS diagnosis was defined as clinical evidence of both upper and lower motor neuron signs in at least three body regions within 18 months of symptom onset. Additional inclusion criteria were a slow vital capacity (SVC) exceeding 60% of the predicted value for a person’s age, sex, and height without being treated with riluzole at the start of the trial or treatment with riluzole at a stable dose for at least 4 weeks prior to screening. Inclusion criteria were revised in August 2017 to include the use of edaravone before and during the trial once available. Participants were excluded if there was a presence of tracheostomy, exposure to sodium phenylbutyrate (PB), taurursodiol (TUDCA or UDCA) within 90 days before screening or planning to use those medications during the study, abnormal liver and renal functions, uncontrolled hypertension, pregnant/ breastfeeding. Both males and females agreed to use adequate birth control during the study