Effect of Pelacarsen on Lipoprotein(a) Cholesterol and Corrected Low-Density Lipoprotein Cholesterol

Yeang, Calvin; Karwatowska‐Prokopczuk, Ewa; Su, Fei; Dinh, Brian; Xia, Shuting; Witztum, Joseph L.; Tsimikas, Sotirios

doi:10.1016/j.jacc.2021.12.032

Cited by 91 publications

(56 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Lp(a) is in fact an LDL cholesterol variant that contains an apolipoprotein(a) [apo(a)] [ 43 ]. Pelacarsen was one of the first drugs in class to be evaluated in humans and is currently in the most advanced phase of clinical trials [ 44 ]. It is an antisense oligonucleotide that binds to hepatocyte apo(a) mRNA and forms an ASO/mRNA complex that prevents the translation of apolipoprotein(a).…”

Section: Resultsmentioning

confidence: 99%

“…Most recent studies have observed lower levels of not only Lp(a), but also lower levels of oxidized phospholipids on apolipoprotein(a) and apolipoprotein(b), lower levels of apolipoprotein(b), and LDL cholesterol. However, the true meaning of this result is questionable as current measurement of LDL cholesterol considers Lp(a) levels, so lower levels of LDL cholesterol might be due to a relative reduction on a count of absolute reduction in Lp(a) [ 44 ]. Pelacarsen is still not an approved drug with phase III clinical trials pending, but results of the trials published so far indicate that Lp(a) lowering certainly led to a decrease in cardiovascular incidents.…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

New Therapeutic Approaches in Treatment of Dyslipidaemia—A Narrative Review

et al. 2022

View full text Add to dashboard Cite

Dyslipidaemia is a well-known risk factor for the development of cardiovascular disease, a leading cause of morbidity and mortality in developed countries. As a consequence, the medical community has been dealing with this problem for decades, and traditional statin therapy remains the cornerstone therapeutic approach. However, clinical trials have observed remarkable results for a few agents effective in the treatment of elevated serum lipid levels. Ezetimibe showed good but limited results when used in combination with statins. Bempedoic acid has been thoroughly studied in multiple clinical trials, with a reduction in LDL cholesterol by approximately 15%. The first approved monoclonal antibodies for the treatment of dyslipidaemia, PCSK9 inhibitors, are currently used as second-line treatment for patients with unregulated lipid levels on statin or statin combination therapy. A new siRNA molecule, inclisiran, demonstrates great potential, particularly concerning compliance, as it is administered twice yearly and pelacarsen, an antisense oligonucleotide that targets lipoprotein(a) and lowers its levels. Volanesorsen is the first drug that was designed to target chylomicrons and lower triglyceride levels, and olezarsen, the next in-line chylomicron lowering agent, is currently being researched. The newest possibilities for the treatment of dyslipidaemia are ANGPTL3 inhibitors with evinacumab, already approved by the FDA, and EMA for the treatment of familial hypercholesterolemia. This article provides a short summary of new agents currently used or being developed for lipid lowering treatment.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

New Therapeutic Approaches in Treatment of Dyslipidaemia—A Narrative Review

et al. 2022

View full text Add to dashboard Cite

show abstract

“…Recent advances of RNA technology have led to the development of Lp(a)-specific oligonucleotide-based therapies, such as mipomersen, which target ApoB ( 25 ); and pelacarsen, which targets Apo(a) ( 26 ). Mipomersen however is more potent for LDL than Lp(a), demonstrating best results in hypercholesterolemia patients ( 27 ), whereas the antisense oligonucleotide, pelacarsen, directly targets the cholesterol portion of Lp(a), Lp(a)-C, reducing levels up to 80% ( 28 ). These agents operate independently of isoform size and genetic variant and have shown promising results in clinical trials, with further therapies such as Amgen’s RNAi ARC-LPa, targeting of LPA mRNA in early development ( 29 ).…”

Section: Discussionmentioning

confidence: 99%

Elevated lipoprotein(a) as a predictor for coronary events in older men

Bartoli-Leonard

Turner

Zimmer

et al. 2022

Journal of Lipid Research

View full text Add to dashboard Cite

“…A study of this drug aims to evaluate efficacy, tolerability, and safety in the treatment of hyperlipoproteinemia. Published data demonstrate a sustained reduction in Lp(a) [46,47], which is favourable for reducing residual cardiovascular risk. N-Acetylgalactosamine-conjugated siRNA, olpasiran, also reduces Lp (a) levels.…”

Section: Perspectivesmentioning

confidence: 99%

European, Russian and American Clinical Guidelines on dyslipidemias management – where do we stand? European, Russian, and US guidelines on dyslipidemias

Alieva

Usova

Reutova

2022

European Atherosclerosis Journal

View full text Add to dashboard Cite

Current clinical guidelines on lipid metabolism disorders are represented by the integration of relevant multicenter observational studies and registries aimed to identify best strategies in cardiovascular risk stratification, diagnostics and treatment of dyslipidemias. The approaches outlined in the European, Russian and American clinical guidelines look relevant to each other despite a range slightly different postulates, as they all demonstrate a general tendency to the importance of accurate risk stratification of patients and timely action on low-density lipoprotein cholesterol (LDL-C) levels when using effective lipid-lowering therapy.

show abstract

Effect of Pelacarsen on Lipoprotein(a) Cholesterol and Corrected Low-Density Lipoprotein Cholesterol

Cited by 91 publications

References 33 publications

New Therapeutic Approaches in Treatment of Dyslipidaemia—A Narrative Review

New Therapeutic Approaches in Treatment of Dyslipidaemia—A Narrative Review

Elevated lipoprotein(a) as a predictor for coronary events in older men

European, Russian and American Clinical Guidelines on dyslipidemias management – where do we stand? European, Russian, and US guidelines on dyslipidemias

Contact Info

Product

Resources

About