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Enlicitide chloride
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 Enlicitide decanoate | |
| Clinical data | |
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| Trade names | Lipfendra |
| Other names | MK-0616, enlicitide decanoate (USAN US) |
| AHFS/Drugs.com | lipfendra |
| License data |
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| Routes of administration | By mouth |
| ATC code |
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| Legal status | |
| Legal status | |
| Identifiers | |
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| CAS Number | |
| PubChem CID | |
| IUPHAR/BPS | |
| UNII | |
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| Chemical and physical data | |
| Formula | C82H110ClFN14O15 |
| Molar mass | 1586.31 g·mol−1 |
| 3D model (JSmol) | |
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Enlicitide chloride, sold under the brand name Lipfendra as the salt enlicitide decanoate, is a medication used for the treatment of hypercholesterolemia (high cholesterol).[1] It is an orally available macrocyclic peptide and a proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor.[1][2][3]
Enlicitide decanoate was approved for medical use in the United States in July 2026.[4][5]
Medical uses
Enlicitide decanoate is indicated as an adjunct to diet and exercise to reduce low-density lipoprotein cholesterol in adults with hypercholesterolemia, including heterozygous familial hypercholesterolemia.[1][5]
Pharmacology
Enlicitide interacts with the LDL receptor binding domain of PCSK9 and inhibits its interaction with the receptor with an IC50 of 2.5 ±0.1 nM.[6]
Enlicitide has poor oral bioavailability and is therefore formulated as the decanoate salt with additional sodium decanoate in the dose.[3][7] Decanoate acts as a stabilizer and permeation enhancer, allowing enlicitide to pass through the intestine and, by temporarily opening tight junctions between intestinal epithelial cells, to cross the intestinal wall.[7] Food in the intestinal tract inhibits this process.[3]
History
Merck developed the drug, applied for US Food and Drug Administration (FDA) approval in 2026,[8] and received approval in July 2026.[9]
In August 2023, Merck launched the phase III CORALreef Lipids clinical trial (NCT05952856[10]) to evaluate the efficacy and safety of enlicitide decanoate (the decanoate salt of MK-0616) in adults with hypercholesterolemia.[11] The study included 2,912 participants.[12][8][13][14]
Also in August 2023, the company launched the CORALreef HeFH trial (NCT05952869) to evaluate the efficacy, safety, and tolerability of enlicitide decanoate in adults with heterozygous familial hypercholesterolemia.[10][15][16]
The efficacy and safety of enlicitide were demonstrated in two randomized, double-blind, placebo-controlled trials (NCT05952856 [CORALreef Lipids] and NCT05952869 [CORALreef HeFH]) in a total of 3,207 adults with severe hypercholesterolemia, including those with and without heterozygous familial hypercholesterolemia, who were already taking maximally tolerated statin therapy.[5] The primary endpoint for both trials was the percent change from baseline to week 24 in LDL-C, compared to placebo.[5] The trials showed enlicitide lowered LDL cholesterol by about 56% to 60% in participants undergoing concurrent lipid-lowering therapy over 24 to 52 weeks. Other lipid parameters also improved, including non-HDL cholesterol, apolipoprotein B, and lipoprotein(a). The safety of oral enlicitide was similar to placebo.[7]
Society and culture
Legal status
Enlicitide decanoate was approved for medical use in the United States in July 2026.[4][5][17]
The US Food and Drug Administration (FDA) granted the application for enlicitide priority review designation.[5] The FDA granted the approval of Lipfendra to Merck Sharp & Dohme.[5]
Names
Enlicitide chloride is the international nonproprietary name.[18]
Enlicitide decanoate is the United States Adopted Name.[19]
Enlicitide decanoate is sold under the brand name Lipfendra.[1][20]
References
- 1 2 3 4 5 "Lipfendra tablet, film coated". DailyMed. 15 July 2026. Retrieved 3 August 2026.
- ↑ Burnett JR, Hooper AJ (2023). "MK-0616: an oral PCSK9 inhibitor for hypercholesterolemia treatment". Expert Opinion on Investigational Drugs. 32 (10): 873–878. doi:10.1080/13543784.2023.2267972. PMID 37815341. S2CID 263802012.
- 1 2 3 4 Siddiqui Z, Frishman W (2025). "New Oral PCSK9 Inhibitor: "MK-0616"". Cardiology in Review. 33 (6): 573–577. doi:10.1097/CRD.0000000000000655. PMID 38285643.
- 1 2 "Novel Drug Approvals for 2026". U.S. Food and Drug Administration (FDA). 22 July 2026. Retrieved 24 July 2026.
- 1 2 3 4 5 6 7 "FDA Approves First Oral Therapy that Inhibits Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) to Lower Bad Cholesterol in Adults with High Cholesterol". U.S. Food and Drug Administration (FDA). 16 July 2026. Retrieved 18 July 2026.
This article incorporates text from this source, which is in the public domain. - ↑ Ferri N, Marodin G (March 2025). "Emerging oral therapeutic strategies for inhibiting PCSK9". Atherosclerosis Plus. 59: 25–31. doi:10.1016/j.athplu.2024.11.003. PMC 11722601. PMID 39802651.
- 1 2 3 Müller-Kozarez I, Laufs U (April 2026). "Phase 3 study results for oral PCSK9 inhibition with enlicitide". Med. 7 (4) 101097. doi:10.1016/j.medj.2026.101097. PMID 41966715.
- 1 2 Kolata G (8 November 2025). "New Pill From Merck Could Slash Cholesterol Levels, Trials Show. The drug targets the PCSK9 protein, and could give millions of people a more affordable option to reduce their heart disease risk". The New York Times.
- ↑ Loftus P (16 July 2026). "FDA Approves First-of-Its-Kind Cholesterol Pill, Ushering In New Wave of Treatment". The Wall Street Journal. Retrieved 16 July 2026.
- 1 2 "Our Pipeline at a glance", 30 April 2026. Merck.com.
- ↑ "A Study of MK-0616 (Oral PCSK9 Inhibitor) in Adults With Hypercholesterolemia (MK-0616-013) CORALreef Lipids". ClinicalTrials.gov. May 2024.
- ↑ Tracy D (3 September 2025). "Merck's Oral PCSK9 Inhibitor Demonstrates Efficacy in Hypercholesterolemia". Applied Clinical Trials. Retrieved 9 November 2025.
- ↑ Navar AM, Mikhailova E, Catapano AL, Banka P, Blom DJ, Cadena A, et al. (February 2026). "A Placebo-Controlled Trial of the Oral PCSK9 Inhibitor Enlicitide". New England Journal of Medicine. 394 (6): 529–539. doi:10.1056/NEJMoa2511002. PMID 41879224. Available via Proquest at The Wikipedia Library
- ↑ Boden WE (February 2026). "Exploring a New "Reef" in Dyslipidemic Risk Reduction". New England Journal of Medicine. 394 (6): 597–599. doi:10.1056/NEJMe2516860. PMID 41885976. Available via Proquest at The Wikipedia Library
- ↑ Clinical trial number NCT05952869 for "A Study of Enlicitide Decanoate (MK-0616 Oral PCSK9 Inhibitor) in Adults With Heterozygous Familial Hypercholesterolemia (MK-0616-017/CORALreef HeFH)" at ClinicalTrials.gov
- ↑ Ballantyne CM, Gellis L, Tardif JC, Banka P, Navar AM, Asprusten EA, et al. (January 2026). "Efficacy and Safety of Oral PCSK9 Inhibitor Enlicitide in Adults With Heterozygous Familial Hypercholesterolemia: A Randomized Clinical Trial". Journal of the American Medical Association. 335 (2): 129–139. doi:10.1001/jama.2025.20620. PMC 12598580. PMID 41206969.
- ↑ "FDA Approves First Oral PCSK9 Inhibitor to Lower LDL Cholesterol in Adults with High Cholesterol". U.S. Food and Drug Administration (FDA) (Press release). 17 July 2026. Retrieved 18 July 2026. This article incorporates text from this source, which is in the public domain.
- ↑ World Health Organization (2023). "International nonproprietary names for pharmaceutical substances (INN): recommended INN: list 90". WHO Drug Information. 37 (3). hdl:10665/373341.
- ↑ https://searchusan.ama-assn.org/usan/documentDownload?uri=/unstructured/binary/usan/enlicitide-decanoate.pdf
- ↑ "Merck's Lipfendra (enlicitide) is the First and Only Once-Daily Oral PCSK9 Inhibitor Approved by the U.S. FDA to Reduce LDL-C in Adults with Hypercholesterolemia" (Press release). Merck. 16 July 2026. Retrieved 18 July 2026 – via Business Wire.
Further reading
- Campeau LC (April 2025). "From Cortisone to Enlicitide: A Journey of Synthetic Chemistry Innovations at Merck". The Journal of Organic Chemistry. 90 (14): 4781–4795. doi:10.1021/acs.joc.4c02919. PMC 11998012. PMID 40168664.
- Klapars A, Fryszkowska A, Galanie S, Ad O, Aguilera EY, Akporji N, et al. (May 2026). "Biocatalytic cascades enable manufacture of the macrocyclic peptide enlicitide". Science (New York, N.Y.). 392 (6798): 643–647. doi:10.1126/science.aed8713. PMID 42096573.
- Li H, Thaisrivongs DA, Shang G, Chen Y, Chen Q, Tan L, et al. (April 2025). "Total Synthesis of Enlicitide Decanoate". Journal of the American Chemical Society. 147 (13): 11036–11048. Bibcode:2025JAChS.14711036L. doi:10.1021/jacs.4c15966. PMID 40123407.
- Masson W, Lobo M, Giunta G, Barbagelata L, Nogueira JP (January 2026). "Lipid-Lowering Efficacy and Safety of Oral Proprotein Convertase Subtilisin/Kexin Type 9 Inhibitors: A Systematic Review and Meta-Analysis". Advances in Therapy. 43 (1): 304–316. doi:10.1007/s12325-025-03418-x. PMC 12858574. PMID 41288928.
External links
- Clinical trial number NCT05952856 for "A Study of Enlicitide Decanoate (MK-0616 Oral PCSK9 Inhibitor) in Adults With Hypercholesterolemia (MK-0616-013) CORALreef Lipids" at ClinicalTrials.gov
- Clinical trial number NCT05952869 for "A Study of Enlicitide Decanoate (MK-0616 Oral PCSK9 Inhibitor) in Adults With Heterozygous Familial Hypercholesterolemia (MK-0616-017/CORALreef HeFH)" at ClinicalTrials.gov
