Sodium phenylbutyrate/ursodoxicoltaurine, also known as sodium phenylbutyrate/taurursodiol and sold under the brand names Albrioza and Relyvrio, is a

fixed-dose combination A combination drug is a combination of two or more pharmaceutical drugs as active ingredients combined into a single dosage form, typically as a ''fixed-dose combination'', with each constituent standardized to specifications of a fixed dose. Fix ...

medication used for the treatment of

amyotrophic lateral sclerosis Amyotrophic lateral sclerosis (ALS), also known as motor neuron disease (MND) or—in the United States—Lou Gehrig's disease (LGD), is a rare, Terminal illness, terminal neurodegenerative disease, neurodegenerative disorder that results i ...

(ALS). It contains

sodium phenylbutyrate Sodium phenylbutyrate, sold under the brand name Buphenyl among others, is a salt of an aromatic fatty acid, 4-phenylbutyrate (4-PBA) or 4-phenylbutyric acid. The compound is used to treat urea cycle disorders, because its metabolites offer an ...

and

ursodoxicoltaurine Ursodoxicoltaurine is the international nonproprietary name (INN) for the pharmaceutical form of tauroursodeoxycholic acid (TUDCA). It is also known as taurursodiol. Tauroursodeoxycholic acid is a naturally occurring hydrophilic bile acid which ...

(taurursodiol). The most common adverse reactions experienced with sodium phenylbutyrate/ursodoxicoltaurine include diarrhea, abdominal pain, nausea and upper respiratory tract infection. Sodium phenylbutyrate/ursodoxicoltaurine acts by blocking

apoptotic Apoptosis (from ) is a form of programmed cell death that occurs in multicellular organisms and in some eukaryotic, single-celled microorganisms such as yeast. Biochemical events lead to characteristic cell changes ( morphology) and death. These ...

pathways in the

mitochondria A mitochondrion () is an organelle found in the cells of most eukaryotes, such as animals, plants and fungi. Mitochondria have a double membrane structure and use aerobic respiration to generate adenosine triphosphate (ATP), which is us ...

and in the

endoplasmic reticulum The endoplasmic reticulum (ER) is a part of a transportation system of the eukaryote, eukaryotic cell, and has many other important functions such as protein folding. The word endoplasmic means "within the cytoplasm", and reticulum is Latin for ...

. Sodium phenylbutyrate is a chemical chaperone that helps proteins maintain their normal conformation, preventing aggregation that may lead to cell death. Ursodoxicoltaurine improves mitochondrial energy production. The combination was approved for medical use in Canada as Albrioza, in June 2022, and in the United States, as Relyvrio, in September 2022. The

European Union The European Union (EU) is a supranational union, supranational political union, political and economic union of Member state of the European Union, member states that are Geography of the European Union, located primarily in Europe. The u ...

's drug regulators refused to approve it, citing concerns about effectiveness. In April 2024, the manufacturer announced that it is withdrawing the medication from the US and Canadian markets, due to it failing a key phase III

clinical trial Clinical trials are prospective biomedical or behavioral research studies on human subject research, human participants designed to answer specific questions about biomedical or behavioral interventions, including new treatments (such as novel v ...

Medical uses

Sodium phenylbutyrate/ursodoxicoltaurine is

indicated In medicine, an indication is a valid reason to use a certain test, medication, procedure, or surgery. There can be multiple indications to use a procedure or medication. An indication can commonly be confused with the term diagnosis. A diagnosis ...

for the treatment of amyotrophic lateral sclerosis (ALS).

History

In the Phase II/III CENTAUR clinical trial, sodium phenylbutyrate/ursodoxicoltaurine (AMX0035) increased survival times for ALS patients. The Phase II PEGASUS clinical trial found that the drug was safe and tolerated by patients with Alzheimer's disease. The efficacy of sodium phenylbutyrate/ursodoxicoltaurine for the treatment of ALS was demonstrated in a 24-week, multi-center, randomized, double-blind, placebo-controlled, parallel-group study. Compared to members of the 137-adult cohort that received a placebo medication, those randomly assigned to treatment with sodium phenylbutyrate/ursodoxicoltaurine showed a slower rate of declining daily functioning and longer overall survival. In September 2022, the United States

Food and Drug Administration The United States Food and Drug Administration (FDA or US FDA) is a List of United States federal agencies, federal agency of the United States Department of Health and Human Services, Department of Health and Human Services. The FDA is respo ...

(FDA) approved

Amylyx Pharmaceuticals Amylyx Pharmaceuticals, Inc is a biopharmaceutical company headquartered in Cambridge, Massachusetts. Amylyx is best known for AMX0035, an experimental therapy for amyotrophic lateral sclerosis. AMX0035 was approved for medical use in Canada as ...

' application for Relyvrio's approval under the

priority review Priority review is a program of the United States Food and Drug Administration (FDA) to expedite the review process for drugs that are expected to have a particularly great impact on the treatment of a disease. The priority review voucher program ...

and

orphan drug An orphan drug is a medication, pharmaceutical agent that is developed to treat certain rare medical conditions. An orphan drug would not be profitable to produce without government assistance, due to the small population of patients affected by th ...

programs. In March 2024, Amylyx Pharmaceuticals announced that its Phase III PHOENIX clinical trial of 664 American and European adults followed over 48 weeks showed no statistically significant difference in the functioning of ALS patients that were randomly assigned to treatment with Relyvrio, as compared to those receiving a placebo drug.

Society and culture

Legal status

The FDA Peripheral and Central Nervous System Drugs Advisory Committee voted not to recommend approval, and then in an unusual second vote recommended approval. In April 2024, after a disappointing phase III trial of the medication failed to produce significant differences versus a placebo, Amylyx announced they would begin the process of withdrawing Albrioza and Relyviro from the North American market.

Economics

In the United States, healthcare insurer

Cigna The Cigna Group is an American multinational for-profit managed healthcare and insurance company based in Bloomfield, Connecticut. Its insurance subsidiaries are major providers of medical, dental, disability, life and accident insurance and r ...

decided, in 2023, to reverse its prior decision to cover the cost of the medication for all ALS patients, opting instead to cover "patients who meet certain clinical criteria", arguing that the drug is "experimental, investigational or unproven". Following the earlier announcement of plans to potentially withdraw the medication, the

Institute for Clinical and Economic Review The Institute for Clinical and Economic Review (ICER) is a Boston-based independent nonprofit organization that seeks to place a value on medical care by providing comprehensive clinical and cost-effectiveness analyses of treatments, tests, and proc ...

criticized the company for pricing the drug at $158,000 per year of treatment, given the uncertainty.

Research

It is being studied as a treatment for

Wolfram syndrome Wolfram syndrome, also called DIDMOAD (diabetes insipidus, diabetes mellitus, optic atrophy, and deafness), is a rare autosomal-recessive genetic disorder that causes childhood-onset diabetes mellitus, optic atrophy, and deafness as well as vario ...

and

progressive supranuclear palsy Progressive supranuclear palsy (PSP) is a late-onset neurodegenerative disease involving the gradual deterioration and death of specific volumes of the brain, linked to 4-repeat tau pathology. The condition leads to symptoms including Balance di ...

, despite the withdrawal of North American marketing authorization for amyotrophic lateral sclerosis (ALS).

References

{{DEFAULTSORT:Sodium Phenylbutyrate Ursodoxicoltaurine Drugs acting on the nervous system Combination drugs Orphan drugs Medical controversies Withdrawn drugs