Enasidenib (

INN Inns are generally establishments or buildings where travelers can seek lodging, and usually, food and drink. Inns are typically located in the country or along a highway; before the advent of motorized transportation they also provided accommo ...

; trade name Idhifa) is a medication used to treat relapsed or refractory

acute myeloid leukemia Acute myeloid leukemia (AML) is a cancer of the myeloid line of blood cells, characterized by the rapid growth of abnormal cells that build up in the bone marrow and blood and interfere with haematopoiesis, normal blood cell production. Sympto ...

in people with specific mutations of the

isocitrate dehydrogenase 2 Isocitrate dehydrogenase ADP mitochondrial is an enzyme that in humans is encoded by the ''IDH2'' gene. Isocitrate dehydrogenases are enzymes that catalyze the oxidative decarboxylation of isocitrate to 2-oxoglutarate. These enzymes belong to two ...

(IDH2) gene, determined by an FDA-approved IDH2 companion diagnostic test. It is an

inhibitor Inhibitor or inhibition may refer to: In biology * Enzyme inhibitor, a substance that binds to an enzyme and decreases the enzyme's activity * Reuptake inhibitor, a substance that increases neurotransmission by blocking the reuptake of a neurotra ...

of IDH2. It was developed by

Agios Pharmaceuticals Agios Pharmaceuticals Inc. is a public American pharmaceutical company pioneering therapies for genetically defined diseases, with a near-term focus on developing therapies for hemolytic anemias. The company was founded in 2008 (or 2007) by Lewis ...

and is licensed to Celgene for further development. The U.S.

Food and Drug Administration The United States Food and Drug Administration (FDA or US FDA) is a federal agency of the Department of Health and Human Services. The FDA is responsible for protecting and promoting public health through the control and supervision of food ...

(FDA) considers it to be a

first-in-class medication A first-in-class medication is a pharmaceutical that uses a "new and unique mechanism of action" to treat a particular medical condition. While the Food and Drug Administration's Center for Drug Evaluation and Research tracks first-in-class medica ...

Medical use

Enasidenib is used to treat relapsed or refractory

in people with specific mutations of the IDH2 gene, determined by an FDA-approved IDH2 companion diagnostic test.

Adverse effects

The main serious adverse effect of enasidenib is

differentiation syndrome Retinoic acid syndrome (RAS) is a potentially life-threatening complication observed in people with acute promyelocytic leukemia (APML) and first thought to be specifically associated with all-''trans'' retinoic acid (ATRA) (also known as tretino ...

Pharmacology

Isocitrate dehydrogenase is a critical enzyme in the

citric acid cycle The citric acid cycle (CAC)—also known as the Krebs cycle or the TCA cycle (tricarboxylic acid cycle)—is a series of chemical reactions to release stored energy through the oxidation of acetyl-CoA derived from carbohydrates, fats, and prote ...

. Mutated forms of IDH produce high levels of the (''R'')-enantiomer of

2-hydroxyglutarate α-Hydroxyglutaric acid (2-hydroxyglutaric acid) is an alpha hydroxy acid form of glutaric acid. In biology In humans the compound is formed by a hydroxyacid-oxoacid transhydrogenase whereas in bacteria is formed by a 2-hydroxyglutarate synth ...

(R-2-HG) and can contribute to the growth of tumors. IDH1 catalyzes this reaction in the cytoplasm, while IDH2 catalyzes this reaction in mitochondria. Mutations of IDH2 are more common than IDH1 mutations, 8 to 19% compared to 7 to 14% respectively, in those affected with AML. Enasidenib disrupts this cycle by decreasing total (R)-2-HG levels in the mitochondria.

History

The U.S.

(FDA) granted the application for enasidenib

fast track The fast track is an informal English term meaning "the quickest and most direct route to achievement of a goal, as in competing for professional advancement". By definition, it implies that a less direct, slower route also exists. Fast track or F ...

designation 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 o ...

designation for

in 2014. Enasidenib was approved by the FDA in August 2017, for relapsed or refractory

(AML) in people with specific mutations of the IDH2 gene, determined by an FDA-approved IDH2 companion diagnostic test.

References

External links

* * * {{Portal bar , Medicine Antineoplastic drugs Bristol Myers Squibb Orphan drugs Pyridines Triazines Trifluoromethyl compounds