enlicitide decanoate (MK-0616) / Merck (MSD), UCB - LARVOL DELTA

Enlicitide Decanoate (MK-0616 Oral PCSK9 Inhibitor) Cardiovascular Outcomes Study (MK-0616-015) CORALreef Outcomes (clinicaltrials.gov) - P3 | N=14550 | Active, not recruiting | Sponsor: Merck Sharp & Dohme LLC | Recruiting ➔ Active, not recruiting

Adverse events • Enrollment closed • Atherosclerosis • Cardiovascular • Dyslipidemia • APOB

A Study of Enlicitide Decanoate (MK-0616, an Oral PCSK9 Inhibitor) in Children and Adolescents With Heterozygous Familial Hypercholesterolemia (MK-0616-029) (clinicaltrials.gov) - P2/3 | N=153 | Not yet recruiting | Sponsor: Merck Sharp & Dohme LLC

New P2/3 trial • Dyslipidemia • Familial Hypercholesterolemia • Genetic Disorders • Heterozygous Familial Hypercholesterolemia • Metabolic Disorders • Pediatrics • APOB

A Clinical Study of How Coffee and Tea Affect Enlicitide in Healthy Volunteers (MK-0616-040) (clinicaltrials.gov) - P1 | N=60 | Not yet recruiting | Sponsor: Merck Sharp & Dohme LLC

New P1 trial

A Clinical Study to Evaluate Enlicitide (MK-0616) Formulations in Healthy Adult Participants (MK-0616-035) (clinicaltrials.gov) - P1 | N=40 | Completed | Sponsor: Merck Sharp & Dohme LLC | Recruiting ➔ Completed

Trial completion

Key takeaways from CORALreef AddOn (Merck (MSD) Press Release) - P3 | N=301 | CORALreef AddOn (NCT06450366) | Sponsor: Merck Sharp & Dohme LLC | "CORALreef AddOn: statistically significant and clinically meaningful reductions in LDL-C for enlicitide versus ezetimibe, versus bempedoic acid and versus ezetimibe and bempedoic acid in adults with hyperlipidemia who have a history of or are at risk for ASCVD and are treated with a statin."

P3 data: top line • Dyslipidemia

Key takeaways from CORALreef HeFH (Merck (MSD) Press Release) - P3 | N=303 | CORALreef HeFH (NCT05952869) | Sponsor: Merck Sharp & Dohme LLC | "CORALreef HeFH: statistically significant and clinically meaningful reductions in LDL-C for enlicitide versus placebo in adults with heterozygous familial hypercholesterolemia (HeFH) who have a history of or are at risk for atherosclerotic cardiovascular disease (ASCVD) and are treated with a statin."

P3 data: top line • Heterozygous Familial Hypercholesterolemia

A Clinical Study of Enlicitide in Participants With Severe Renal Impairment (MK-0616-032) (clinicaltrials.gov) - P1 | N=24 | Active, not recruiting | Sponsor: Merck Sharp & Dohme LLC | Recruiting ➔ Active, not recruiting

Enrollment closed • Renal Disease

A Clinical Study of Enlicitide Decanoate in People With Liver Function Problems (MK-0616-030) (clinicaltrials.gov) - P1 | N=20 | Completed | Sponsor: Merck Sharp & Dohme LLC | Active, not recruiting ➔ Completed | N=40 ➔ 20

Enrollment change • Trial completion • Hepatitis C • Hepatology • Liver Failure

A Study to Evaluate the Efficacy and Safety of Enlicitide Decanoate (MK-0616, Oral PCSK9 Inhibitor) Compared With Ezetimibe or Bempedoic Acid or Ezetimibe and Bempedoic Acid in Adults With Hypercholesterolemia (MK-0616-018) CORALreef AddOn (clinicaltrials.gov) - P3 | N=301 | Completed | Sponsor: Merck Sharp & Dohme LLC | Active, not recruiting ➔ Completed

Trial completion • Dyslipidemia • Metabolic Disorders • APOB

A Study of Enlicitide Decanoate (MK-0616 Oral PCSK9 Inhibitor) in Adults With Heterozygous Familial Hypercholesterolemia (MK-0616-017) CORALreef HeFH (clinicaltrials.gov) - P3 | N=303 | Completed | Sponsor: Merck Sharp & Dohme LLC | Active, not recruiting ➔ Completed

Trial completion • Dyslipidemia • Familial Hypercholesterolemia • Genetic Disorders • Heterozygous Familial Hypercholesterolemia • Metabolic Disorders • APOB

Oral and Non-Oral Cholesterol-Lowering Drugs with PCSK9 and Other Biomolecules as Targets: Present Status and Future Prospects. (PubMed, Biomolecules) - "This review provides an overview of the existing cholesterol-lowering drugs, and the progress made so far with oral-based PCSK9 drugs for lowering LDL-cholesterol. The review is presented in several sections highlighting the molecular targets, the individual drugs, and the modes of administration, with a focus on the oral route."

Journal • Review • Cardiovascular • Dyslipidemia • Pain

Oral PCSK9 Inhibitors: Will They Work? (PubMed, Curr Atheroscler Rep) - "Enlicitide decanoate (formerly known as MK-0616) has been shown to significantly reduce LDL-C levels by a maximum of 66% from baseline with a good safety and tolerability profile...AZD0780 is another oral small molecule that lowers LDL-C levels by 52% and can be administered on top of a statin...If the results of the outcome studies will be positive, we will have a safe, effective and easy-to-use oral therapy. Oral PCSK9 inhibitors could provide a convenient alternative to injectable PCSK9 inhibitors and result in a greater number of patients receiving an effective LDL-C-lowering therapy."

Journal • Review • Atherosclerosis • Cardiovascular • Dyslipidemia

A Clinical Study of Enlicitide Decanoate in People With Liver Function Problems (MK-0616-030) (clinicaltrials.gov) - P1 | N=40 | Active, not recruiting | Sponsor: Merck Sharp & Dohme LLC | Recruiting ➔ Active, not recruiting

Enrollment closed • Hepatitis C • Hepatology • Liver Failure

A Clinical Study to Evaluate Enlicitide (MK-0616) Formulations in Healthy Adult Participants (MK-0616-035) (clinicaltrials.gov) - P1 | N=40 | Recruiting | Sponsor: Merck Sharp & Dohme LLC | Not yet recruiting ➔ Recruiting

Enrollment open

Total Synthesis of Enlicitide Decanoate. (PubMed, J Am Chem Soc) - "It is a highly complex macrocyclic peptide with a significant number of nonpeptide structural elements that presents a daunting synthetic chemistry challenge. We describe the development of a convergent, efficient, and robust manufacturing process that enables the large-scale production of enlicitide."

Journal • Atherosclerosis • Cardiovascular

A Clinical Study to Evaluate Enlicitide (MK-0616) Formulations in Healthy Adult Participants (MK-0616-035) (clinicaltrials.gov) - P1 | N=40 | Not yet recruiting | Sponsor: Merck Sharp & Dohme LLC

New P1 trial

From lead to market: chemical approaches to transform peptides into therapeutics. (PubMed, Trends Biochem Sci) - "In this review, we explore two recent therapeutic candidates (semaglutide, a peptide hormone analogue, and MK-0616, an mRNA display-derived candidate) as case studies that highlight general approaches to improving pharmacokinetics (PK) and potency. We also emphasize the critical link between advances in medicinal chemistry and the optimisation of highly efficacious peptide therapeutics."

Journal • Review

A Study to Evaluate the Efficacy and Safety of Enlicitide Decanoate (MK-0616, Oral PCSK9 Inhibitor) Compared With Ezetimibe or Bempedoic Acid or Ezetimibe and Bempedoic Acid in Adults With Hypercholesterolemia (MK-0616-018) CORALreef AddOn (clinicaltrials.gov) - P3 | N=301 | Active, not recruiting | Sponsor: Merck Sharp & Dohme LLC | Trial primary completion date: Jul 2025 ➔ Feb 2025 | Trial completion date: Sep 2025 ➔ Apr 2025

Trial completion date • Trial primary completion date • Dyslipidemia • Metabolic Disorders

A Study of Lithium and Enlicitide in Healthy Adult Participants (MK-0616-034) (clinicaltrials.gov) - P1 | N=16 | Completed | Sponsor: Merck Sharp & Dohme LLC | Active, not recruiting ➔ Completed

Trial completion

A Clinical Study of Enlicitide and the Effect of Food in Healthy Adult Participants (MK-0616-033) (clinicaltrials.gov) - P1 | N=20 | Completed | Sponsor: Merck Sharp & Dohme LLC | Active, not recruiting ➔ Completed

Trial completion

A Single- and Multiple-Dose Study of Enlicitide Chloride (MK-0616) in Healthy Chinese Adult Participants (MK 0616-010) (clinicaltrials.gov) - P1 | N=37 | Completed | Sponsor: Merck Sharp & Dohme LLC

New P1 trial

A Study of Lithium and Enlicitide in Healthy Adult Participants (MK-0616-034) (clinicaltrials.gov) - P1 | N=16 | Active, not recruiting | Sponsor: Merck Sharp & Dohme LLC | Recruiting ➔ Active, not recruiting

Enrollment closed

Emerging oral therapeutic strategies for inhibiting PCSK9. (PubMed, Atheroscler Plus) - "Subcutaneous administration of monoclonal antibodies (evolocumab and alirocumab) every 2 or 4 weeks determined a 60 % reduction of LDL cholesterol levels, while the GalNac-siRNA anti PCSK9 (inclisiran) provided an effective lipid lowering activity (-50 %) after an initial subcutaneous dose, repeated after 3 months and followed by a maintenance dose every 6 months. These problems could be overcome by the development of small chemical molecules anti PCSK9 as oral therapy for controlling hypercholesterolemia. In the present review, we summarized the pharmacological properties of oral anti PCSK9 molecules that are currently under clinical development (DC371739, CVI-LM001, and AZD0780), including the mimetic peptides enlicitide decanoate (MK-0616) and NNC0385-0434."

Journal • Review • Cardiovascular • Dyslipidemia • Metabolic Disorders

A Study to Evaluate the Drug-Drug Interaction Between Enlicitide Decanoate (MK-0616) and Alendronate in Healthy Adult Participants (MK-0616-027) (clinicaltrials.gov) - P1 | N=36 | Completed | Sponsor: Merck Sharp & Dohme LLC

New P1 trial

A Study of Enlicitide Decanoate (MK-0616), Warfarin, and Lisinopril in Healthy Adult Participants (MK-0616-026) (clinicaltrials.gov) - P1 | N=36 | Completed | Sponsor: Merck Sharp & Dohme LLC

New P1 trial