All articles tagged with #pcsk9
Two distinct experimental approaches are emerging to tackle high LDL cholesterol without daily medication. A CRISPR-based therapy, VERVE-102, showed a 62% reduction in bad cholesterol in a human trial, while a DNA-based molecule, HpE12, cut cholesterol by 47% in mice. Both target the PCSK9 protein, which regulates cholesterol clearance, offering potential alternatives to statins and current injectable inhibitors.
A new study in Nature demonstrates that base editing can efficiently modify the PCSK9 gene in human embryos without causing the severe DNA damage typical of Cas9 tools. While embryos developed normally to the blastocyst stage, researchers observed rare chromosomal abnormalities and off-target edits, concluding that the technology is not yet safe for clinical reproductive use.
The FDA has approved Lipfendra (enlicitide), Merck’s oral PCSK9 inhibitor, to lower LDL-C in patients not adequately controlled on statins. As the first oral option in this class, enlicitide is a macrocyclic peptide designed to disrupt PCSK9-LDL receptor interactions and is produced via a biocatalytic process using 13 engineered enzymes. Because it’s a pill rather than an injectable antibody, it could be prescribed by general practitioners, expanding access, though cost and adherence remain concerns; patients must fast for 30 minutes after dosing for full absorption.
Merck is betting Lipfendra—the first oral PCSK9 inhibitor—will unlock a sluggish market after gaining July FDA approval via the Commissioner’s National Priority Voucher (CNPV) program, with initial demand rising but payer access likely slow; priced at $315 per month and supported by a direct-to-patient discount plan, Merck sees long-term blockbuster potential and is exploring combos with rosuvastatin and MK-7262, plus an outcomes study due in 2029.
The US FDA approved Lipfendra, the world’s first oral PCSK9 inhibitor, for adults with high cholesterol including heterozygous familial hypercholesterolaemia, offering an injectable-free option. In trials, it reduced LDL cholesterol by about 56–59% over 24 weeks in patients on maximally tolerated statins, with effectiveness comparable to injectable PCSK9 inhibitors. It is unlikely to be a first-line therapy, and it won’t be available in India immediately, as CDSCO clearance (and possibly local trials) would be required. Doctors say it could help patients who prefer oral treatment or struggle with injections.
A 47-year-old woman with autoimmune Hashimoto’s thyroiditis who had total thyroidectomy showed dramatic LDL-C elevations during profound hypothyroidism, driven by reduced LDL receptor activity and increased PCSK9; LDL-C levels improved markedly when euthyroidism was restored with levothyroxine. The case highlights hypothyroidism as a reversible, non-genetic cause of severe hypercholesterolemia and emphasizes evaluating thyroid function before diagnosing familial hypercholesterolemia or initiating lipid-lowering therapy.
FDA-approved enlicitide is an oral pill that lowers LDL cholesterol by about 60%, offering a needle-free alternative to injections and statins for those who can’t tolerate them; the drug’s development builds on PCSK9 genetics, and while LDL reductions look promising, hard outcomes like deaths will take years to prove, and cost and access—alongside the potential of gene editing and other therapies—will shape how broadly it helps curb heart disease.
Merck’s cholesterol pill Lipfendra (enlicitide) was approved by the FDA, becoming the first oral PCSK9 inhibitor on the market and offering an alternative to injectable cholesterol drugs. The decision was based on two late‑stage trials showing significant LDL‑C reductions across a broad patient group, including those with familial hypercholesterolemia and statin users. The drug could help Merck diversify beyond Keytruda, with analysts forecasting potential tens of billions in peak sales amid competition from injectable PCSK9 drugs like Repatha and Praluent.
In a small Phase I study, Verve Therapeutics’ VERVE-102, a one-time mRNA-based gene-editing therapy targeting PCSK9, reduced LDL by up to 62% in the highest-dose group among 35 participants, with no serious safety events aside from a transient mild rise in a liver enzyme; results suggest durable LDL-C lowering, but larger and longer trials are needed for confirmation, and the FDA has granted Fast Track designation.
A DNA-based treatment using polypurine hairpins to silence PCSK9 lowers LDL cholesterol and boosts LDL receptors. In liver cells HpE9/HpE12 reduced PCSK9 RNA by up to 74% and protein by up to 87%; in transgenic mice a single injection cut PCSK9 by ~50% and cholesterol by ~47% within days, potentially offering a statin-free alternative with fewer side effects.
A phase 3 trial of the daily oral PCSK9 inhibitor enlicitide showed LDL cholesterol falls by about 60% in 2,909 patients with atherosclerosis or high cardiovascular risk, many already on statins. The pill also reduced non-HDL cholesterol, apolipoprotein B, and lipoprotein(a), with effects lasting one year. If FDA approves, enlicitide could offer an oral alternative to injectable PCSK9 therapies and improve adherence, though a separate study is needed to confirm whether these LDL reductions translate into fewer heart attacks and strokes. The trial was Merck-funded and ongoing work aims to determine cardiovascular event outcomes.
Merck has developed a new pill called enlicitide that significantly reduces LDL cholesterol levels by blocking the PCSK9 protein, showing promising results in clinical trials with a 20% reduction in heart attack and stroke rates among high-risk patients, and offering a potentially more affordable alternative to existing injectable treatments.
Researchers have developed a new therapy using polypurine hairpins to inhibit PCSK9, significantly reducing LDL cholesterol levels by nearly 50% without the side effects associated with statins, offering a promising alternative for managing hypercholesterolemia and preventing atherosclerosis.
A new genetic therapy using polypurine hairpins to inhibit PCSK9 significantly reduces cholesterol levels by nearly 50%, offering a promising alternative to traditional statins and potentially reducing cardiovascular disease risk.
A patent case before the US Supreme Court over rights to therapeutic antibodies that are used to treat high cholesterol could have far-reaching impacts on drug prices and technology. The decision could affect how specific patents of any ilk must be when they describe an invention, and how broad they can be. A win by Amgen could hinder the development of new medicines by restricting competition and discouraging the development of multiple therapeutic antibodies that bind to the same target.