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

Evolution of LDL-C Lowering Medications and Their Cardiovascular Benefits: Past, Present, and Future. (PubMed, Curr Probl Cardiol) - "Major landmark cardiovascular outcome clinical trials demonstrated that LDL-C lowering medications reduce cardiovascular events, and the lower the LDL-C the better the outcome. This article discusses the evolution of LDL-C lowering medications starting from bile acid sequestrants (BAS), statin therapy, bempedoic acid, the proprotein convertase subtilisin kexin 9 (PCSK9) synthesis inhibitor, novel small interfering RNA-based therapy (inclisiran) to the most recent oral PCSK9 inhibitors (MK-0616) which is currently under phase 3 clinical trial studies."

Journal • Review • Cardiovascular • Dyslipidemia

Oral PCSK9 Inhibitors. (PubMed, Curr Atheroscler Rep) - "Clinical trial data on the safety and efficacy of MK-0616 are promising and report LDL-C-lowering efficacy comparable to that provided by injectable PCSK9 inhibitors. Ongoing and future studies of oral PCSK9 inhibitors in development will evaluate the safety, efficacy, and effectiveness of these agents and their potential role in preventing cardiovascular disease events."

Journal • Review • Cardiovascular

A Study of MK-0616 (Oral PCSK9 Inhibitor) in Adults With Heterozygous Familial Hypercholesterolemia (MK-0616-017) CORALreef HeFH (clinicaltrials.gov) - P3 | N=270 | Active, not recruiting | Sponsor: Merck Sharp & Dohme LLC | Trial completion date: Sep 2025 ➔ Apr 2025 | Trial primary completion date: Sep 2025 ➔ Apr 2025

Trial completion date • Trial primary completion date • Dyslipidemia • Familial Hypercholesterolemia • Genetic Disorders • Heterozygous Familial Hypercholesterolemia • Metabolic Disorders

MK-0616 (Oral PCSK9 Inhibitor) Renal Impairment Study 2 (MK-0616-020) (clinicaltrials.gov) - P1 | N=33 | Completed | Sponsor: Merck Sharp & Dohme LLC | Active, not recruiting ➔ Completed

Trial completion • Dyslipidemia • Renal Disease

The translational potential of miR-26 in atherosclerosis and development of agents for its target genes ACC1/2, COL1A1, CPT1A, FBP1, DGAT2, and SMAD7. (PubMed, Cardiovasc Diabetol) - "Many agents targeting these genes, such as the ACC1/2 inhibitors GS-0976, PF-05221304, and MK-4074; the DGAT2 inhibitors IONIS-DGAT2Rx, PF-06427878, PF-0685571, and PF-07202954; the COL1A1 inhibitor HT-100; the stimulants Ga-CBP8 and RCT-01; the CPT1A inhibitors etomoxir, perhexiline, and teglicar; the FBP1 inhibitors CS-917 and MB07803; and the SMAD7 inhibitor mongersen, have been investigated in clinical trials...Many PCSK9 inhibitors, including alirocumab, evolocumab, inclisiran, AZD8233, Civi-007, MK-0616, and LIB003, have been investigated in clinical trials...Multiple materials can be used to deliver miR-26, but it is unclear which material is most suitable for mass production and clinical applications. This review focuses on the potential use of miR-26 in treating atherosclerosis to support the development of agents targeting it."

Journal • Review • Atherosclerosis • Cardiovascular • Dyslipidemia • Gastrointestinal Cancer • Hepatocellular Cancer • Oncology • Solid Tumor • ABCA1 • ACACA • ACSL3 • BMP2 • CD36 • COL1A1 • CPT1A • CTGF • EHHADH • HMGB1 • IFNA1 • IL1B • IL6 • MALT1 • RUNX2 • SCARB1 • SMAD7 • TCF7L2 • TNFA

New Oral PCSK9 Inhibitor: "MK-0616". (PubMed, Cardiol Rev) - "The results achieved so far are promising for individuals with hypercholesterolemia, as they offer a potential solution for effectively lowering low-density lipoprotein cholesterol in patients on statin therapy and mitigating the risk of cardiovascular events. Ongoing research and monitoring will be critical to establish its long-term safety and efficacy, but MK-0616 may emerge as a valuable addition to the array of lipid-lowering therapies available to patients."

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

PCSK9-directed therapies: an update. (PubMed, Curr Opin Lipidol) - "Long-term inhibition of PCSK9 with monoclonal antibodies is safe and conveys sustained cardiovascular benefit. Novel strategies to inhibit PCSK9 function such as orally available drugs, RNA targeting, and one-time treatment with gene editing may further enhance the therapeutic armamentarium and enable novel preventive strategies."

Journal • Cardiovascular

A Study of MK-0616 (Oral PCSK9 Inhibitor) in Adults With Heterozygous Familial Hypercholesterolemia (MK-0616-017) CORALreef HeFH (clinicaltrials.gov) - P3 | N=270 | Active, not recruiting | Sponsor: Merck Sharp & Dohme LLC | Recruiting ➔ Active, not recruiting

Enrollment closed • Dyslipidemia • Familial Hypercholesterolemia • Genetic Disorders • Heterozygous Familial Hypercholesterolemia • Metabolic Disorders

MK-0616 (Oral PCSK9 Inhibitor) Renal Impairment Study 2 (MK-0616-020) (clinicaltrials.gov) - P1 | N=36 | Active, not recruiting | Sponsor: Merck Sharp & Dohme LLC | Recruiting ➔ Active, not recruiting | Trial completion date: Jun 2024 ➔ Jan 2024 | Trial primary completion date: Jun 2024 ➔ Jan 2024

Enrollment closed • Trial completion date • Trial primary completion date • Dyslipidemia • Renal Disease

A Study of the Efficacy and Safety of MK-0616 (Oral PCSK9 Inhibitor) in Adults With Hypercholesterolemia (MK-0616-008) (clinicaltrials.gov) - P2 | N=381 | Completed | Sponsor: Merck Sharp & Dohme LLC | Phase classification: P2b ➔ P2

Phase classification • Dyslipidemia • Familial Hypercholesterolemia • Genetic Disorders • Metabolic Disorders

MK-0616: an oral PCSK9 inhibitor for hypercholesterolemia treatment. (PubMed, Expert Opin Investig Drugs) - "MK-0616 may offer advantages over injectable anti-PCSK9 therapies in terms of ease of dosing, patient preference and cost. The results from phase III trials of MK-0616 on cardiovascular outcomes are awaited with interest."

Journal • Review • Atherosclerosis • Cardiovascular • Dyslipidemia • Metabolic Disorders • APOB

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

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

A Study of MK-0616 (Oral PCSK9 Inhibitor) in Adults With Heterozygous Familial Hypercholesterolemia (MK-0616-017) CORALreef HeFH (clinicaltrials.gov) - P3 | N=270 | Recruiting | Sponsor: Merck Sharp & Dohme LLC | Not yet recruiting ➔ Recruiting

Enrollment open • Dyslipidemia • Familial Hypercholesterolemia • Genetic Disorders • Heterozygous Familial Hypercholesterolemia • Metabolic Disorders • APOB

A Study of MK-0616 (Oral PCSK9 Inhibitor) in Adults With Hypercholesterolemia (MK-0616-013) CORALreef Lipids (clinicaltrials.gov) - P3 | N=2760 | Recruiting | Sponsor: Merck Sharp & Dohme LLC | Not yet recruiting ➔ Recruiting

Enrollment open • Dyslipidemia • Familial Hypercholesterolemia • Genetic Disorders • Metabolic Disorders • APOB

MK-0616 (Oral PCSK9 Inhibitor) Cardiovascular Outcomes Study (MK-0616-015) (clinicaltrials.gov) - P3 | N=14550 | Not yet recruiting | Sponsor: Merck Sharp & Dohme LLC

Adverse events • New P3 trial • Atherosclerosis • Cardiovascular • Dyslipidemia • APOB

MK-0616 (Oral PCSK9 Inhibitor) Renal Impairment Study 2 (MK-0616-020) (clinicaltrials.gov) - P1 | N=36 | Recruiting | Sponsor: Merck Sharp & Dohme LLC | Not yet recruiting ➔ Recruiting

Enrollment open • Dyslipidemia • Renal Disease

A Study of MK-0616 (Oral PCSK9 Inhibitor) in Adults With Heterozygous Familial Hypercholesterolemia (MK-0616-017) (clinicaltrials.gov) - P3 | N=270 | Not yet recruiting | Sponsor: Merck Sharp & Dohme LLC

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

A Study of MK-0616 (Oral PCSK9 Inhibitor) in Adults With Hypercholesterolemia (MK-0616-013) (clinicaltrials.gov) - P3 | N=2760 | Not yet recruiting | Sponsor: Merck Sharp & Dohme LLC

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

MK-0616 (Oral PCSK9 Inhibitor) Renal Impairment Study 2 (MK-0616-020) (clinicaltrials.gov) - P1 | N=36 | Not yet recruiting | Sponsor: Merck Sharp & Dohme LLC

New P1 trial • Dyslipidemia • Renal Disease

A Study of MK-0616 in Participants With Moderate Renal Impairment (MK-0616-007) (clinicaltrials.gov) - P1 | N=18 | Completed | Sponsor: Merck Sharp & Dohme LLC | Active, not recruiting ➔ Completed

Trial completion • Renal Disease

Highlights of Cardiovascular Disease Prevention Studies Presented at the 2023 American College of Cardiology Conference. (PubMed, Curr Atheroscler Rep) - "The CLEAR outcomes randomized control trial (RCT) compared bempedoic acid to placebo in patients at high-risk of cardiovascular disease (CVD) or prevalent CVD and statin intolerance for CV outcomes. The YELLOW III was a single-arm study that evaluated the effect of Evolocumab on coronary plaque characteristics in patients with stable coronary artery disease (CAD)...A Phase 2B RCT compared the efficacy of an oral PCSK9i, MK-0616, in reducing LDL-C as compared to a placebo. The late-breaking clinical science presented at the 2023 conference of the ACC paves the way for an evidence-based alternative to statin therapy and provides data on several common clinical scenarios encountered in daily practice."

Journal • Review • Acute Coronary Syndrome • Atherosclerosis • Cardiovascular • Coronary Artery Disease • Dyslipidemia

Orally Bioavailable Macrocyclic Peptide That Inhibits Binding of PCSK9 to the Low Density Lipoprotein Receptor. (PubMed, Circulation) - "This work validates the use of mRNA display technology for identification of novel oral therapeutic agents, exemplified by the identification of an oral PCSK9 inhibitor, which has the potential to be a highly effective cholesterol lowering therapy for patients in need."

Journal • Dyslipidemia

A Study of MK-0616 in Participants With Moderate Renal Impairment (MK-0616-007) (clinicaltrials.gov) - P1 | N=18 | Active, not recruiting | Sponsor: Merck Sharp & Dohme LLC | Recruiting ➔ Active, not recruiting

Enrollment closed • Renal Disease

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Dyslipidemia • Immunology • Metabolic Disorders • Osteoarthritis • Pain • Rheumatology • NLRP3

Efficacy and safety of the oral PCSK9 inhibitor MK-0616: a phase 2b randomized controlled trial. (PubMed, J Am Coll Cardiol) - P2b | "MK-0616 demonstrated statistically significant and robust, dose-dependent placebo-adjusted reductions in LDL-C at Week 8 of up to 60.9% from baseline and was well tolerated over 8 weeks of treatment and an additional 8 weeks of follow up."

Clinical • Journal • P2b data • Dyslipidemia • Metabolic Disorders