Obicetrapib

Obicetrapib
Clinical data
Other names	TA-8995; AMG-899
Legal status
Legal status	Investigational;
Identifiers
	IUPAC name 4-[2-{{#parsoidfragment:1}}3,5-bis(trifluoromethyl)phenyl]methyl-[(2R,4S)-1-ethoxycarbonyl-2-ethyl-6-(trifluoromethyl)-3,4-dihydro-2H-quinolin-4-yl]amino]pyrimidin-5-yl]oxybutanoic acid;
CAS Number	866399-87-3;
PubChem CID	11498596;
DrugBank	DB14890;
ChemSpider	9673402;
UNII	8O74K609HN;
KEGG	D12900;
ChEMBL	ChEMBL3785197;
Chemical and physical data
Formula	C32H31F9N4O5
Molar mass	722.609 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES CC[C@@H]1C[C@@H](C2=C(N1C(=O)OCC)C=CC(=C2)C(F)(F)F)N(CC3=CC(=CC(=C3)C(F)(F)F)C(F)(F)F)C4=NC=C(C=N4)OCCCC(=O)O;
	InChI InChI=1S/C32H31F9N4O5/c1-3-22-14-26(24-13-19(30(33,34)35)7-8-25(24)45(22)29(48)49-4-2)44(28-42-15-23(16-43-28)50-9-5-6-27(46)47)17-18-10-20(31(36,37)38)12-21(11-18)32(39,40)41/h7-8,10-13,15-16,22,26H,3-6,9,14,17H2,1-2H3,(H,46,47)/t22-,26+/m1/s1; Key:NRWORBQAOQVYBJ-GJZUVCINSA-N;

Obicetrapib is an experimental CETP inhibitor that is intended to treat dyslipidemia. In a clinical trial, as an add-on to statins, compared with placebo, it decreased concentrations of LDL-C (by up to 51%), apolipoprotein B (by up to 30%) and non-high-density lipoprotein cholesterol (non-HDL-C) (by up to 44%), and increased HDL-C concentration (by up to 165%).^[1]^[2] As of 2023, it is in a Phase III trial.^[3]

History

Obicetrapib was initially developed by Amgen as AMG-899 and was abandoned in 2017.^[4] In 2020, Amgen licensed the drug to NewAmsterdam Pharma.^[5] In 2022, NewAmsterdam Pharma licensed the drug to Menarini Group.^[6]

References

↑ Ballantyne, Christie M.; Ditmarsch, Marc; Kastelein, John JP; Nelson, Adam J.; Kling, Douglas; Hsieh, Andrew; Curcio, Danielle L.; Maki, Kevin C.; Davidson, Michael H.; Nicholls, Stephen J. (July 2023). "Obicetrapib plus ezetimibe as an adjunct to high-intensity statin therapy: A randomized phase 2 trial". Journal of Clinical Lipidology. 17 (4): 491–503. doi:10.1016/j.jacl.2023.05.098. PMID 37277261.
↑ Nicholls, Stephen J.; Ditmarsch, Marc; Kastelein, John J.; Rigby, Scott P.; Kling, Douglas; Curcio, Danielle L.; Alp, Nicholas John; Davidson, Michael H. (August 2022). "Lipid lowering effects of the CETP inhibitor obicetrapib in combination with high-intensity statins: a randomized phase 2 trial". Nature Medicine. 28 (8): 1672–1678. doi:10.1038/s41591-022-01936-7. ISSN 1546-170X. PMID 35953719.
↑ "NewAmsterdam Pharma concludes enrolment in LDL lowering therapy trial". Clinical Trials Arena. 26 July 2023.
↑ Amgen kills off CETP inhibitor after seeing Merck data
↑ NewAmsterdam bags $196M to resurrect Amgen's discarded CETP drug
↑ "Menarini Group's Obicetrapib and Obicetrapib/Ezetimibe Marketing Authorisation Applications Accepted for Review by the European Medicines Agency (EMA) for the Treatment of adults with primary hypercholesterolaemia (Heterozygous familial and non-familial)".

[1] Ballantyne, Christie M.; Ditmarsch, Marc; Kastelein, John JP; Nelson, Adam J.; Kling, Douglas; Hsieh, Andrew; Curcio, Danielle L.; Maki, Kevin C.; Davidson, Michael H.; Nicholls, Stephen J. (July 2023). "Obicetrapib plus ezetimibe as an adjunct to high-intensity statin therapy: A randomized phase 2 trial". Journal of Clinical Lipidology. 17 (4): 491–503. doi:10.1016/j.jacl.2023.05.098. PMID 37277261.

[2] Nicholls, Stephen J.; Ditmarsch, Marc; Kastelein, John J.; Rigby, Scott P.; Kling, Douglas; Curcio, Danielle L.; Alp, Nicholas John; Davidson, Michael H. (August 2022). "Lipid lowering effects of the CETP inhibitor obicetrapib in combination with high-intensity statins: a randomized phase 2 trial". Nature Medicine. 28 (8): 1672–1678. doi:10.1038/s41591-022-01936-7. ISSN 1546-170X. PMID 35953719.

[3] "NewAmsterdam Pharma concludes enrolment in LDL lowering therapy trial". Clinical Trials Arena. 26 July 2023.

[4] Amgen kills off CETP inhibitor after seeing Merck data

[5] NewAmsterdam bags $196M to resurrect Amgen's discarded CETP drug

[6] "Menarini Group's Obicetrapib and Obicetrapib/Ezetimibe Marketing Authorisation Applications Accepted for Review by the European Medicines Agency (EMA) for the Treatment of adults with primary hypercholesterolaemia (Heterozygous familial and non-familial)".

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