Enlicitide pill reduces LDL cholesterol by 60% in phase 3 trial

An experimental oral pill called enlicitide lowered LDL cholesterol by about 60% in a large phase three clinical trial, according to results published in The New England Journal of Medicine. The trial, led by Dr. Ann Marie Navar at UT Southwestern Medical Center and sponsored by Merck, involved 2,909 participants mostly already on statins. If approved, the daily pill could improve access to effective cholesterol treatment.

The phase three trial tested enlicitide, an oral PCSK9 inhibitor, against a placebo in 2,909 participants with atherosclerosis or at risk due to related conditions. Most were taking statins, with average LDL levels at 96 mg/dl, above targets of 70 mg/dl for those with atherosclerosis and 55 mg/dl for at-risk individuals. After 24 weeks, enlicitide reduced LDL by about 60% compared to placebo, with benefits sustained over a year. It also lowered non-HDL cholesterol, apolipoprotein B, and lipoprotein(a).

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Clinical illustration of nurse giving single-dose zilebesiran injection to hypertension patient, with blood pressure monitor showing reduction from KARDIA-2 trial results.
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Single-dose zilebesiran as add-on therapy lowers systolic blood pressure in KARDIA-2 trial

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A single, under-the-skin dose of the investigational RNA-interference drug zilebesiran lowered blood pressure when added to standard therapy in adults whose hypertension remained uncontrolled, according to results from the global Phase 2 KARDIA-2 trial of 663 participants published in JAMA.

Researchers from Mass General Brigham found that the cholesterol drug evolocumab cuts the risk of first-time major cardiovascular events by 31% in high-risk patients with diabetes who lack diagnosed atherosclerosis. The results, from a subgroup analysis of the VESALIUS-CV trial, were presented at the American College of Cardiology's Annual Scientific Session and published in JAMA. Patients on the drug saw LDL cholesterol levels drop significantly alongside standard treatments.

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Researchers from the University of Barcelona and the University of Oregon report that short DNA molecules known as polypurine reverse Hoogsteen hairpins (PPRHs) suppressed the PCSK9 gene and reduced blood cholesterol in a mouse model. In transgenic mice carrying the human PCSK9 gene, a single injection of one candidate (HpE12) cut plasma PCSK9 by 50% and total cholesterol by 47% three days later, according to findings published in Biochemical Pharmacology.

A large international randomized trial found that 4 grams a day of omega-3 fish oil was associated with a 43% lower rate of serious cardiovascular events among adults receiving maintenance hemodialysis. The PISCES study enrolled 1,228 participants at 26 sites in Australia and Canada; results were presented at the American Society of Nephrology’s Kidney Week 2025 and published in The New England Journal of Medicine.

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Researchers at Oregon Health & Science University have created a molecule called SU212 that blocks a key enzyme in triple-negative breast cancer cells. In mouse models, the compound reduced tumor growth and metastasis. The findings offer potential new treatment options for this hard-to-treat form of the disease.

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