Omaveloxolone, sold under the brand name Skyclarys, is a
medication used for the treatment of
Friedreich's ataxia.
[ ] It is taken
by mouth.
The most common side effects include an increase in alanine transaminase and an increase of aspartate aminotransferase, which can be signs of liver damage, headache, nausea, abdominal pain, fatigue, diarrhea and musculoskeletal pain.
Omaveloxolone was approved for medical use in the United States in February 2023.
The US
Food and Drug Administration (FDA) considers it to be a
first-in-class medication.
Medical uses
Omaveloxolone 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 Friedreich's ataxia.
Friedreich's ataxia causes progressive damage to the spinal cord, peripheral nerves, and the brain, resulting in uncoordinated muscle movement, poor balance, difficulty walking, changes in speech and swallowing, and a shortened lifespan.
The condition can also cause heart disease.
This disease tends to develop in children and teenagers and gradually worsens over time.
Although rare, Friedreich's ataxia is the most common form of hereditary ataxia in the United States, affecting about one in every 50,000 people.
Mechanism of action
The mechanism of action of omaveloxolone and its related compounds has been demonstrated to be through a combination of activation of the antioxidative transcription factor
Nrf2 and inhibition of the pro-inflammatory transcription factor
NF-κB.
transcriptionally regulates multiple genes that play both direct and indirect roles in producing antioxidative potential and the production of cellular energy (''i.e.'', adenosine triphosphate or
ATP
ATP may refer to:
Companies and organizations
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) within the
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 ...
. Consequently, unlike exogenously administered
antioxidants (''e.g.'',
vitamin E or
Coenzyme Q10
Coenzyme Q, also known as ubiquinone and marketed as CoQ10, is a coenzyme family that is ubiquitous in animals and most bacteria (hence the name ubiquinone). In humans, the most common form is coenzyme Q10 or ubiquinone-10.
It is a 1,4-benzoq ...
), which provide a specific and finite antioxidative potential, omaveloxolone, through Nrf2, broadly activates intracellular and mitochondrial antioxidative pathways, in addition to pathways that may directly increase
mitochondrial biogenesis (such as
PGC1α) and
bioenergetics
Bioenergetics is a field in biochemistry and cell biology that concerns energy flow through living systems. This is an active area of biological research that includes the study of the transformation of energy in living organisms and the study of ...
.
History
Omaveloxolone is a second generation member of the synthetic oleanane triterpenoid compounds and in clinical development by
Reata Pharmaceuticals.
Preclinical studies have demonstrated that omaveloxolone possesses
antioxidative
Antioxidants are Chemical compound, compounds that inhibit Redox, oxidation, a chemical reaction that can produce Radical (chemistry), free radicals. This can lead to polymerization and other chain reactions. They are frequently added to indust ...
and
anti-inflammatory activities
and the ability to improve
mitochondrial bioenergetics.
Omaveloxolone is under clinical investigation for a variety of indications, including
Friedreich's ataxia,
mitochondrial myopathies,
immunooncology, and prevention of
corneal endothelial cell loss following
cataract surgery.
The efficacy and safety of omaveloxolone was evaluated in a 48-week randomized, placebo-controlled, and double-blind study
tudy 1 (NCT02255435)and an open-label extension.
Study 1 enrolled 103 individuals with Friedreich's ataxia who received placebo (52 individuals) or omaveloxolone 150 mg (51 individuals) for 48 weeks.
Of the research participants, 53% were male, 97% were white, and the mean age was 24 years at study entry.
Nine (18%) patients were younger than age 18.
The primary objective was to evaluate the change in the modified Friedreich's Ataxia Rating Scale (mFARS) score compared to placebo at week 48.
The mFARS is a clinical assessment that measures disease progression, namely swallowing and speech (bulbar), upper limb coordination, lower limb coordination, and upright stability.
Individuals receiving omaveloxolone performed better on the mFARS than people receiving placebo.
The US
Food and Drug Administration (FDA) granted the application for omaveloxolone
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 ...
,
fast track,
priority review, and rare pediatric disease designations.
Society and culture
Legal status
Omaveloxolone was approved for medical use in the United States in February 2023.
In December 2023, the
Committee for Medicinal Products for Human Use (CHMP) of the
European Medicines Agency
The European Medicines Agency (EMA) is an agency of the European Union (EU) in charge of the evaluation and supervision of medicinal products. Prior to 2004, it was known as the European Agency for the Evaluation of Medicinal Products or Euro ...
adopted a positive opinion, recommending the granting of a marketing authorization for the medicinal product Skyclarys, intended for the treatment of Friedreich's ataxia.
The applicant for this medicinal product is Reata Ireland Limited.
[ Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.]
References
External links
*
{{Authority control
Organofluorides
Orphan drugs
Steroids
Triterpenes