Bempedoic acid/ezetimibe

Bempedoic acid/ezetimibe, sold under the name Nexlizet among others, is a combination drug used as an adjunct with diet and maximally tolerated statin therapy for the treatment of adults with heterozygous familial hypercholesterolemia or established atherosclerotic cardiovascular disease who require additional lowering of LDL-C.[1] It is a combination of bempedoic acid and ezetimibe.[1][2]

Bempedoic acid/ezetimibe

Combination of
Bempedoic acid	adenosine triphosphate-citrate lyase (ACL) inhibitor
Ezetimibe	cholesterol absorption inhibitor
Clinical data
Trade names	Nexlizet, Nustendi
AHFS/Drugs.com	Nexlizet
License data	EU EMA: by INN US DailyMed: Nexlizet US FDA: Nexlizet
Routes of administration	By mouth
ATC code	none
Legal status
Legal status	US: ℞-only In general: ℞ (Prescription only)
Identifiers
CAS Number	738606-46-7^Y 163222-33-1^Y
PubChem CID	10472693 150311
IUPHAR/BPS	8321 6816
DrugBank	DB11936 DB00973
ChemSpider	8648104 132493
UNII	1EJ6Z6Q368 EOR26LQQ24^Y
KEGG	D11794
ChEBI	CHEBI:49040
ChEMBL	ChEMBL3545313 ChEMBL1138
Chemical and physical data
3D model (JSmol)	Interactive image Interactive image
SMILES CC(C)(CCCCCC(CCCCCC(C)(C)C(=O)O)O)C(=O)O C1=CC(=CC=C1C2C(C(=O)N2C3=CC=C(C=C3)F)CCC(C4=CC=C(C=C4)F)O)O
InChI InChI=1S/C19H36O5/c1-18(2,16(21)22)13-9-5-7-11-15(20)12-8-6-10-14-19(3,4)17(23)24/h15,20H,5-14H2,1-4H3,(H,21,22)(H,23,24) Key:HYHMLYSLQUKXKP-UHFFFAOYSA-N InChI=1S/C24H21F2NO3/c25-17-5-1-15(2-6-17)22(29)14-13-21-23(16-3-11-20(28)12-4-16)27(24(21)30)19-9-7-18(26)8-10-19/h1-12,21-23,28-29H,13-14H2/t21-,22+,23-/m1/s1 Key:OLNTVTPDXPETLC-XPWALMASSA-N

The most common side effects are hyperuricaemia (high blood levels of uric acid) and constipation.[2]

It the EU it must not be used in pregnant or breast-feeding women.[2] Use during pregnancy is not recommended in the US.[1]

The combination was approved for medical use in the United States in February 2020, and in the European Union in March 2020.[3][2]

Bempedoic acid is an adenosine triphosphate-citrate lyase (ACL) inhibitor and ezetimibe is a cholesterol absorption inhibitor.[1] Bempedoic acid works by blocking an enzyme in the liver called adenosine triphosphate citrate lyase, which is involved in making cholesterol.[2] Ezetimibe works by binding to a gut protein called 'Niemann-Pick C1 Like 1', preventing cholesterol from being absorbed into the blood from the gut.[2]

Medical uses

In the US bempedoic acid/ezetimibe is indicated as an adjunct to diet and maximally tolerated statin therapy for the treatment of adults with heterozygous familial hypercholesterolemia or established atherosclerotic cardiovascular disease who require additional lowering of LDL-C.[1]

In the EU bempedoic acid/ezetimibe is indicated in adults with primary hypercholesterolaemia (heterozygous familial and non-familial) or mixed dyslipidaemia, as an adjunct to diet:[2]

• in combination with a statin in people unable to reach LDL-C goals with the maximum tolerated dose of a statin in addition to ezetimibe[2]
• alone in people who are either statin-intolerant or for whom a statin is contraindicated, and are unable to reach LDL-C goals with ezetimibe alone,[2]
• in people already being treated with the combination of bempedoic acid and ezetimibe as separate tablets with or without statin[2]

History

The European Medicines Agency (EMA) recommended approval or bempedoic acid/ezetimibe (Nustendi) in the EU in January 2020.[4]

Bempedoic acid/ezetimibe was approved in the United States in February 2020, and in the European Union in March 2020.[3][5][2]

Two studies showed that bempedoic acid and ezetimibe effectively reduced LDL cholesterol levels in subjects with hypercholesterolaemia and heart disease or who were at high risk of heart disease.[2] High cholesterol is a risk factor for heart disease.[2]

The first study involved 382 subjects also taking the maximum tolerated doses of statins.[2] After three months, LDL cholesterol levels were reduced by 36% in subjects taking bempedoic acid and ezetimibe compared with a reduction of 23% with ezetimibe alone, 17% with bempedoic acid alone and an increase of around 2% with placebo (a dummy treatment).[2]

The second study involved 269 subjects with high cholesterol levels who were not able to take a statin or were taking a low dose of a statin.[2] All the subjects were also taking ezetimibe.[2] After three months, LDL cholesterol levels were reduced by 23% in subjects taking bempedoic acid in addition to ezetimibe compared with an increase of around 5% in subjects taking placebo and ezetimibe.[2]

References

1. "Nexlizet- bempedoic acid and ezetimibe tablet, film coated". DailyMed. 10 March 2020. Retrieved 19 March 2020.
2. "Nustendi EPAR". European Medicines Agency. 29 January 2020. Retrieved 24 April 2020. This article incorporates text from this source, which is in the public domain.
3. "Drug Approval Package: Nexlizet". U.S. Food and Drug Administration (FDA). 17 April 2020. Retrieved 24 April 2020.
4. "Nustendi: Pending EC decision". European Medicines Agency (EMA). 30 January 2020. Retrieved 21 February 2020.
5. "Nexlizet: FDA-Approved Drugs". U.S. Food and Drug Administration (FDA). Retrieved 26 February 2020.

External links

• "Bempedoic acid". Drug Information Portal. U.S. National Library of Medicine.
• "Ezetimibe". Drug Information Portal. U.S. National Library of Medicine.
• Clinical trial number NCT03337308 for "A Study Evaluating the Safety and Efficacy of Bempedoic Acid Plus Ezetimibe Fixed-Dose Combination Compared to Bempedoic Acid, Ezetimibe, and Placebo in Patients Treated With Maximally Tolerated Statin Therapy" at ClinicalTrials.gov