Sodium phenylbutyrate/ursodoxicoltaurine, also known as sodium phenylbutyrate/taurursodiol and sold under the brand name Albrioza among others, is a

fixed-dose combination A combination drug or a fixed-dose combination (FDC) is a medicine that includes two or more active ingredients combined in a single dosage form. Terms like "combination drug" or "combination drug product" can be common shorthand for a FDC prod ...

medication used for the treatment of

amyotrophic lateral sclerosis Amyotrophic lateral sclerosis (ALS), also known as motor neuron disease (MND) or Lou Gehrig's disease, is a neurodegenerative disease that results in the progressive loss of motor neurons that control voluntary muscles. ALS is the most comm ...

(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 (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

cell death Cell death is the event of a biological cell ceasing to carry out its functions. This may be the result of the natural process of old cells dying and being replaced by new ones, as in programmed cell death, or may result from factors such as dis ...

pathways in

mitochondria A mitochondrion (; ) is an organelle found in the Cell (biology), cells of most Eukaryotes, such as animals, plants and Fungus, fungi. Mitochondria have a double lipid bilayer, membrane structure and use aerobic respiration to generate adenosi ...

and in the

endoplasmic reticulum The endoplasmic reticulum (ER) is, in essence, the transportation system of the eukaryotic cell, and has many other important functions such as protein folding. It is a type of organelle made up of two subunits – rough endoplasmic reticulum ( ...

. Sodium phenylbutyrate is a

chemical chaperone Chemical chaperones are a class of small molecules that function to enhance the folding and/or stability of proteins. Chemical chaperones are a broad and diverse group of molecules, and they can influence protein stability and polypeptide organizati ...

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.

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

(ALS).

History

In a phase II/III clinical trial, CENTAUR, for ALS sodium phenylbutyrate/ursodoxicoltaurine (AMX0035) showed increased survival times. A phase II trial for Alzheimer's disease, PEGASUS, confirmed the safety and tolerability of sodium phenylbutyrate/ursodoxicoltaurine. 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. In the trial, 137 adult participants with ALS were randomized to receive either sodium phenylbutyrate/ursodoxicoltaurine or placebo. The participants treated with sodium phenylbutyrate/ursodoxicoltaurine experienced a slower rate of decline on a clinical assessment of daily functioning compared to those receiving a placebo. Additionally, longer overall survival was observed in a post hoc, long-term analysis of participants who originally received sodium phenylbutyrate/ursodoxicoltaurine versus those who originally received placebo. The US

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 respon ...

(FDA) granted the application for the combination

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 pharmaceutical agent developed to treat medical conditions which, because they are so rare, would not be profitable to produce without government assistance. The conditions are referred to as orphan diseases. The assignment of ...

designations. The FDA granted the approval of Relyvrio to Amylyx Pharmaceuticals Inc.

Society and culture

Controversies

The FDA approval is controversial because of the small size of the trial. The FDA Peripheral and Central Nervous System Drugs Advisory Committee voted not to recommend approval, and then in an unusual second vote recommended approval.

Research

It is being studied as a treatment for

Alzheimer's disease Alzheimer's disease (AD) is a neurodegeneration, neurodegenerative disease that usually starts slowly and progressively worsens. It is the cause of 60–70% of cases of dementia. The most common early symptom is difficulty in short-term me ...

and

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 variou ...

References

External links

* * {{DEFAULTSORT:Sodium Phenylbutyrate Ursodoxicoltaurine Drugs acting on the nervous system Combination drugs Orphan drugs