Lomitapide

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Lomitapide
Lomitapide skeletal.svg
Systematic (IUPAC) name
N-(2,2,2-Trifluoroethyl)-9-[4-[4-[[[4'-(trifluoromethyl)[1,1'-biphenyl]2-yl]carbonyl]amino]-1-piperidinyl]butyl]9H-fluoren-9-carboxamde
Clinical data
Trade names Juxtapid (US), Lojuxta (EU)
Licence data EMA:Link, US FDA:link
Pregnancy cat.
Legal status
Routes Oral
Identifiers
CAS number 182431-12-5 YesY
202914-84-9 (mesilate)
ATC code C10AX12
PubChem CID 9853053
UNII 82KUB0583F YesY
KEGG D09637 YesY
ChEBI CHEBI:72297 N
Synonyms AEGR-773, BMS-201038
Chemical data
Formula C39H37F6N3O2 
Mol. mass 693.719 g/mol
 N (what is this?)  (verify)

Lomitapide (INN, marketed as Juxtapid in the US and as Lojuxta in the EU) is a drug for the treatment of familial hypercholesterolemia, developed by Aegerion Pharmaceuticals.[1] It has been tested in clinical trials as single treatment and in combinations with atorvastatin, ezetimibe and fenofibrate.[2][3]

The US Food and Drug Administration (FDA) approved lomitapide on 21 December 2012, as an orphan drug to reduce LDL cholesterol, total cholesterol, apolipoprotein B, and non-high-density lipoprotein (non-HDL) cholesterol in patients with homozygous familial hypercholesterolemia (HoFH).[4]

On 31 May 2013 the European Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion with a unanimous vote recommending a marketing authorization for lomitapide.[5] On 31 July 2013 the European Commission approved lomitapide as an adjunct to a low-fat diet and other lipid-lowering medicinal products with or without low density lipoprotein (LDL) apheresis in adult patients with HoFH.

Mechanism of action[edit]

Lomitapide inhibits the microsomal triglyceride transfer protein (MTP or MTTP) which is necessary for very low-density lipoprotein (VLDL) assembly and secretion in the liver.[1][6]

On 24 December 2012, drug manufacturer Aegerion announced they had been approved by the FDA to as "an adjunct to a low-fat diet and other lipid-lowering treatments...in patients with homozygous familial hypercholesterolemia (HoFH)."[7][8]

Side effects[edit]

In a Phase III study, lomitapide lead to elevated aminotransferase levels and fat accumulation in the liver.[6]

References[edit]

  1. ^ a b H. Spreitzer (12 March 2007). "Neue Wirkstoffe – BMS-201038". Österreichische Apothekerzeitung (in German) (6/2007): 268. 
  2. ^ Samaha, Frederick F; James McKenney; LeAnne T Bloedon; William J Sasiela; Daniel J Rader (2008). "Impact of the MTP-Inhibitor, AEGR-733, as Monotherapy and in Combination with Ezetimibe on Lipid Subfractions as Measured by NMR Spectroscopy". Circulation 118 (5): 469. doi:10.1161/CIRCULATIONAHA.108.792689. PMID 18663098. 
  3. ^ Aegerion Pharmaceuticals, Inc. Announces AEGR-733 Phase II Data Demonstrates Significant Lowering of LDL Cholesterol with Promising Hepatic Safety Profile
  4. ^ "FDA approves new orphan drug for rare cholesterol disorder"
  5. ^ European Medicines Agency: Lojuxta
  6. ^ a b Cuchel, M.; Bloedon, L. T.; Szapary, P. O.; Kolansky, D. M.; Wolfe, M. L.; Sarkis, A.; Millar, J. S.; Ikewaki, K.; Siegelman, E. S.; Gregg, R. E.; Rader, D. J. (2007). "Inhibition of Microsomal Triglyceride Transfer Protein in Familial Hypercholesterolemia". New England Journal of Medicine 356 (2): 148–156. doi:10.1056/NEJMoa061189. PMID 17215532.  edit
  7. ^ "FDA Approves Juxtapid for Homozygous Familial Hypercholesteolemia". 26 December 2012. 
  8. ^ "FDA Approves Aegerion Pharmaceuticals' Juxtapid (lomitapide) Capsules for Homozygous Familial Hypercholesterolemia (HoFH)" (Press release). Aegerion Pharmaceuticals. 24 December 2012. 

External links[edit]