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.

An experimental therapy called VERVE-102 lowered LDL cholesterol by up to 62 percent after a single dose in an early safety study. The results come from a Phase I trial involving 35 patients with high cholesterol or early cardiovascular disease. Data were published this week in the New England Journal of Medicine.

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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.

New data presented at the European Renal Association’s 63rd Congress in Glasgow and published in three major medical journals found that finerenone slowed kidney-function decline in adults with chronic kidney disease (CKD) without diabetes and reduced the risk of a combined kidney-and-cardiovascular outcome. A separate pooled analysis that combined results across finerenone studies also reported fewer kidney and heart-failure events in a broader CKD population.

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Adults with gout who reduced blood urate to guideline targets within a year of starting urate-lowering therapy had a lower risk of heart attack, stroke or cardiovascular death over the next five years, according to an analysis of more than 109,000 patients in UK electronic health records published in JAMA Internal Medicine.

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