Lipfendra (enlicitide) / Merck (MSD), UCB - LARVOL DELTA

Oral PCSK9 inhibitors: closing the gap between potency and practicality. (PubMed, Curr Opin Lipidol) - "Oral PCSK9 inhibitors have the potential to improve the convenience and acceptability of PCSK9-targeted therapy. Whether these advantages translate into greater real-world uptake will depend on affordability, payer coverage, clinician adoption, and long-term adherence."

Journal • Cardiovascular

A Clinical Trial of Enlicitide (MK-0616) Formulations in Healthy Participants (MK-0616-044) (clinicaltrials.gov) - P1 | N=30 | Active, not recruiting | Sponsor: Merck Sharp & Dohme LLC | Recruiting ➔ Active, not recruiting

Enrollment closed

Evolocumab for high cardiovascular risk patients without previous stroke: a network meta-analysis of randomized controlled trials (ESC 2026) - "Purpose: To investigate the efficacy and safety of non-statin treatments—including evolocumab, alirocumab, enlicitide, inclisiran, evinacumab, omega-3 fatty acids, and ezetimibe—in high CV risk patients without previous stroke. Evolocumab had the potential to be the first-line non-statin option for high CV risk patients without previous stroke due to its efficacy in reducing MACE, CV mortality, LDL-C, and Lp(a)."

Retrospective data • Cardiovascular • Dyslipidemia • Myocardial Infarction

A Clinical Study of Enlicitide (MK-0616) in Adults With Hyperlipidemia in India (MK-0616-038) (clinicaltrials.gov) - P3 | N=150 | Not yet recruiting | Sponsor: Merck Sharp & Dohme LLC

New P3 trial • Dyslipidemia • Familial Hypercholesterolemia • Metabolic Disorders • APOB

Enlicitide Decanoate. (PubMed, Am J Health Syst Pharm) - No abstract available

Journal

Evaluating enlicitide decanoate: first oral PCSK9 inhibitor for the treatment of adults with hypercholesterolemia. (PubMed, Expert Opin Pharmacother) - "Available data on enlicitide are also compared with existing lipid-lowering therapies, including statins, ezetimibe, and approved therapies targeting PCSK9. Enlicitide decanoate is a promising addition to lipid-lowering therapy, potentially expanding access to PCSK9 inhibition through oral administration. However, its definitive clinical role will depend on cardiovascular outcomes data, long-term safety, adherence in real-world practice, and cost-effectiveness compared with established injectable therapies."

Journal • Review • Atherosclerosis • Cardiovascular • Dyslipidemia • Familial Hypercholesterolemia • Genetic Disorders • Heterozygous Familial Hypercholesterolemia • Metabolic Disorders

Long-Term Efficacy and Safety of Enlicitide in an Open-Label Extension Study (AHA 2026) - "Abstract is embargoed at this time."

Clinical

Efficacy of Enlicitide on LDL-C Reduction Across PREVENT Cardiovascular Risk Categories in the Phase 3 CORALreef Lipids Study (AHA 2026) - "Abstract is embargoed at this time."

Clinical • P3 data • Cardiovascular

Efficacy of enlicitide across ESC cardiovascular risk categories in two CORALreef phase 3 trials (ESC 2026) - "Conclusions Across ESC cardiovascular risk strata, enlicitide achieved robust reductions in LDL-C, non-HDL-C, ApoB, and Lp(a), with profoundly higher LDL-C and ApoB goal attainment versus placebo. Amid the global cardiovascular disease epidemic, these findings highlight enlicitide’s potential to meaningfully reduce atherogenic lipids across a broad cardiovascular risk spectrum and help more patients achieve LDL-C and ApoB goals."

Clinical • P3 data • Cardiovascular • Dyslipidemia • APOB

Efficacy of enlicitide, an oral PCSK9 inhibitor, across baseline Lp(a) strata in an analysis of two phase 3 trials (ESC 2026) - "In this pooled analysis of phase 3 trials, baseline Lp(a) levels varied by race. Treatment with enlicitide resulted in significant Lp(a) reductions across all baseline Lp(a) levels and across racial and ethnic subgroups with the largest % reductions in those with Lp(a) levels between 13.7 and 150.2 nmol, and largest absolute reductions in those with Lp(a) levels ≥125 nmol/L and ≥ 39.6 nmol/L. Placebo corrected %LDL-C reduction with enlicitide was >60% and consistent across the full range of baseline Lp(a) levels."

Clinical • P3 data • Atherosclerosis • Cardiovascular • Dyslipidemia

Enlicitide (Lipfendra) - an oral PCSK9 inhibitor for LDL-cholesterol lowering. (PubMed, Med Lett Drugs Ther) - No abstract available

Journal • Dyslipidemia • Metabolic Disorders

Enlicitide, a Novel Oral Macrocyclic Peptide PCSK9 Inhibitor for Lipid Lowering: A Systematic Review and Meta-Analysis. (PubMed, J Cardiovasc Dev Dis) - "Enlicitide demonstrated substantial lipid-lowering efficacy with an acceptable safety profile. The ongoing CORALreef Outcomes trial will determine whether these lipid improvements translate into reductions in major adverse cardiovascular events."

Journal • Retrospective data • Review • Cardiovascular • Dyslipidemia • Familial Hypercholesterolemia • Genetic Disorders • Heterozygous Familial Hypercholesterolemia • Metabolic Disorders • APOB

A Clinical Trial of Enlicitide (MK-0616) Formulations in Healthy Participants (MK-0616-044) (clinicaltrials.gov) - P1 | N=30 | Recruiting | Sponsor: Merck Sharp & Dohme LLC | Not yet recruiting ➔ Recruiting

Enrollment open

Chemoenzymatic synthesis of Enlicitide: Scalable biocatalytic route to complex macrocyclic peptides (ACS-Fall 2026) - "This work demonstrates a sustainable, scalable approach for the manufacture of complex peptide therapeutics. In this presentation, I will highlight a key enzymatic cascade showcasing how biocatalysis and protein engineering enable practical large-scale synthesis of intricate macrocyclic peptides."

Dyslipidemia • Metabolic Disorders

One pot, five enzyme cascade that enables a protecting group free amidation and reductive amination to access an advanced intermediate to MK 0616, an orally available PCSK9 inhibitor (ACS-Fall 2026) - "Its three fused macrocycles and high functional complexity make it extremely challenging to manufacture, with the first reported chemical route requiring 43 steps and delivered less than 1% overall yield. This talk will describe the development of a one pot, five enzyme cascade that enables a protecting group free amidation and reductive amination to access an advanced intermediate en route to MK 0616, ultimately enabling its long term manufacture."

Metastases • Atherosclerosis • Cardiovascular

Manufacturing process for the macrocyclic peptide enlicitide (ACS-Fall 2026) - "Enlicitide decanoate (MK-0616) is a novel macrocyclic peptide that has demonstrated oral bioavailability and significant reductions in LDL-C in Phase 3 trials. This talk will highlight how our team is harnessing the power of biocatalysis to build an efficient, scalable route for enlicitide decanoate."

Atherosclerosis • Cardiovascular • Dyslipidemia • Metabolic Disorders

Journey to manufacture the PCSK9 inhibitor enlicitide decanoate (ACS-Fall 2026) - "It is a highly complex macrocyclic peptide with significant non-peptide structural elements, posing a daunting synthetic chemistry challenge. This talk will cover the development of a convergent, efficient, and robust manufacturing process that enables the large-scale production of enlicitide, an unprecedentedly large "small" molecule."

Atherosclerosis • Cardiovascular • Dyslipidemia • Metabolic Disorders

Behind Enlicitide: From lead screening to drug candidate (ACS-Fall 2026) - "Installing two new cross-links in the top and middle regions of the molecule synergistically improved potency and protease stability, bringing the series into picomolar potency. These combined structural and biophysical optimizations during early discovery enabled the identification of Enlicitide."

A Clinical Trial of Enlicitide (MK-0616) Formulations in Healthy Participants (MK-0616-044) (clinicaltrials.gov) - P1 | N=30 | Not yet recruiting | Sponsor: Merck Sharp & Dohme LLC

New P1 trial

Enlicitide: The first oral PCSK9 inhibitor approved for treatment of hypercholesterolemia. (PubMed, Drug Discov Ther) - "Statins remain the cornerstone of lipid-lowering therapy, while ezetimibe and injectable proprotein convertase subtilisin/kexin 9 (PCSK9) targeted agents are added when further LDL-C reduction is required. Nevertheless, those trials primarily evaluated LDL-C reduction rather than cardiovascular outcomes, and their duration was insufficient to establish long-term safety. The ongoing CORALreef Outcomes trial will determine whether enlicitide-mediated LDL-C reduction translates into fewer major cardiovascular events and will help define its long-term clinical role."

Journal • Atherosclerosis • Cardiovascular • Coronary Artery Disease • Dyslipidemia • Heart Failure • Heterozygous Familial Hypercholesterolemia • Ischemic stroke • Metabolic Disorders • Peripheral Arterial Disease

Efficacy and Safety of Oral PCSK9 Inhibitors in Adults With Hypercholesterolemia: An Updated and GRADE Assessed Systematic Review and Meta-Analysis of Randomised Controlled Trials. (PubMed, Diabetes Obes Metab) - "Oral PCSK9 inhibitors were associated with clinically meaningful improvements in multiple lipid parameters while maintaining a favourable short-term safety profile. However, the available evidence is derived primarily from short-term randomised trials evaluating surrogate lipid outcomes. Larger randomised trials with longer follow-up and cardiovascular outcome data are needed to better define the long-term clinical role of oral PCSK9 inhibitors."

Journal • Retrospective data • Cardiovascular • Dyslipidemia • Metabolic Disorders • APOB

A Clinical Study of Enlicitide in Participants With High Cholesterol (MK-0616-037) (clinicaltrials.gov) - P3 | N=975 | Active, not recruiting | Sponsor: Merck Sharp & Dohme LLC | Trial completion date: Mar 2027 ➔ Nov 2026 | Trial primary completion date: Dec 2026 ➔ Aug 2026

Trial completion date • Trial primary completion date • Dyslipidemia • APOB

A Clinical Study of MK-7262 and Enlicitide in Healthy Participants (MK-7262-003) (clinicaltrials.gov) - P1 | N=30 | Active, not recruiting | Sponsor: Merck Sharp & Dohme LLC | Recruiting ➔ Active, not recruiting

Enrollment closed

Merck…announced the U.S. Food and Drug Administration (FDA) has approved LIPFENDRA (enlicitide) tablets 20 mg as an adjunct to diet and exercise to reduce low-density lipoprotein cholesterol (LDL-C) in adults with hypercholesterolemia, including heterozygous familial hypercholesterolemia (HeFH) (Businesswire) - "The approval is based on two Phase 3 trials from the CORALreef clinical program: CORALreef Lipids and CORALreef HeFH. In CORALreef Lipids, LIPFENDRA reduced LDL-C by 56% compared to placebo at week 24....In CORALreef HeFH, LIPFENDRA reduced LDL-C by 59% at week 24 compared to placebo."

FDA approval • Heterozygous Familial Hypercholesterolemia

A Clinical Trial of MK-7262 and Enlicitide in Participants With High Lipoprotein(a) (MK-7262-004) (clinicaltrials.gov) - P2 | N=750 | Recruiting | Sponsor: Merck Sharp & Dohme LLC | Not yet recruiting ➔ Recruiting

Enrollment open • Monotherapy