Mipomersen in Familial Hypercholesterolemia: An Update on Health-Related Quality of Life and Patient-Reported Outcomes

Chambergo‐Michilot, Diego; Alur, Anish; Kulkarni, Saneel; Agarwala, Anandita

doi:10.2147/vhrm.s191965

Cited by 34 publications

(27 citation statements)

References 34 publications

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“…Overall, the injection of fesomersen as a single s.c. dose up to 120 mg had a favorable safety profile and was well tolerated in all three studies. There were no reported local cutaneous reactions at the injection site or flu‐like reactions, which are often observed with other ASO drugs, 12–14 and no severe bleeding potentially related to inhibition of FXI production. The QTc analyses of healthy participants suggested no effect of fesomersen on the cardiac re‐ and de‐polarization durations for single doses up to 120 mg and multiple doses up to 80 mg.…”

Section: Discussionmentioning

confidence: 91%

Pharmacokinetics, pharmacodynamics, and safety of fesomersen, a novel antisense inhibitor of factor XI, in healthy Chinese, Japanese, and Caucasian volunteers

Liu,

Hashizume,

Krieg

et al. 2024

Clinical Translational Sci

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The inhibition of coagulation factor XI (FXI) presents an attractive approach for anticoagulation as it is not expected to increase the risk of clinically relevant bleeding and is anticipated to be at least as effective as currently available anticoagulants. Fesomersen is a conjugated antisense oligonucleotide that selectively inhibits the expression of FXI. The article describes three clinical studies that investigated the safety, pharmacokinetic (PK), and pharmacodynamic (PD) profiles of fesomersen after subcutaneous (s.c.) injection to healthy participants. The studies included participants from diverse ethnic backgrounds (Caucasian, Japanese, and Chinese). Fesomersen demonstrated good safety and tolerability in all three studies. No major bleeding events were observed. After single‐dose s.c. injection, fesomersen was rapidly absorbed into the systemic circulation, with maximum fesomersen‐equivalent (fesomersen‐eq) concentrations (Cmax) in plasma observed within a few hours. After reaching Cmax, plasma fesomersen‐eq concentrations declined in a biphasic fashion. The PD analyses showed that the injection of fesomersen led to dose‐dependent reductions in FXI activity and increases in activated partial thromboplastin time (aPTT). The maximum observed PD effects were reached between Day 15 and 30, and FXI activity and aPTT returned to near‐baseline levels by Day 90 after a single dose. The PK/PD profiles after a single injection were similar among the various ethnic groups. Collectively, the study results suggest that fesomersen has a favorable safety profile and predictable and similar PK and PD profiles across Chinese, Japanese, and Caucasian participants.

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Section: Discussionmentioning

confidence: 91%

Pharmacokinetics, pharmacodynamics, and safety of fesomersen, a novel antisense inhibitor of factor XI, in healthy Chinese, Japanese, and Caucasian volunteers

Liu,

Hashizume,

Krieg

et al. 2024

Clinical Translational Sci

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“…147,148 The extremely low levels of apoB-containing lipoproteins in these patients actually spurred the development of drugs to reduce the risk of ASCVD despite the fact they might induce steatotic liver disease. [149][150][151] SAR1B deficiency is a third Mendelian disorder highlighting the impact of attenuated trafficking of apoB-containing lipoproteins (OMIM#246700). In this case, low plasma lipids are also accompanied by steatotic liver disease, but these patients primarily experience the consequences of lack of fat-soluble vitamins due to defective absorption of dietary lipids in the gut as discussed elsewhere.…”

Section: Translationmentioning

confidence: 99%

VLDL Biogenesis and Secretion: It Takes a Village

van Zwol,

van de Sluis,

Ginsberg

et al. 2024

Circulation Research

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The production and secretion of VLDLs (very-low-density lipoproteins) by hepatocytes has a direct impact on liver fat content, as well as the concentrations of cholesterol and triglycerides in the circulation and thus affects both liver and cardiovascular health, respectively. Importantly, insulin resistance, excess caloric intake, and lack of physical activity are associated with overproduction of VLDL, hepatic steatosis, and increased plasma levels of atherogenic lipoproteins. Cholesterol and triglycerides in remnant particles generated by VLDL lipolysis are risk factors for atherosclerotic cardiovascular disease and have garnered increasing attention over the last few decades. Presently, however, increased risk of atherosclerosis is not the only concern when considering today’s cardiometabolic patients, as they often also experience hepatic steatosis, a prevalent disorder that can progress to steatohepatitis and cirrhosis. This duality of metabolic risk highlights the importance of understanding the molecular regulation of the biogenesis of VLDL, the lipoprotein that transports triglycerides and cholesterol out of the liver. Fortunately, there has been a resurgence of interest in the intracellular assembly, trafficking, degradation, and secretion of VLDL by hepatocytes, which has led to many exciting new molecular insights that are the topic of this review. Increasing our understanding of the biology of this pathway will aid to the identification of novel therapeutic targets to improve both the cardiovascular and the hepatic health of cardiometabolic patients. This review focuses, for the first time, on this duality.

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“…Mipomersen ometa proizvodnju Apo B koji se nalazi u sastavu LDL-h, VLDL i Lp (a) 46 . Mipomersen značajno snižava LDL-h, non-HDL-h, Lp (a), TG i Apo B. U Americi je 2012. godine bila odobrena supkutana primena leka u dozi od 200 mg kod pacijenata sa HoFH.…”

Section: Mipomersenunclassified

“…Mipomersen značajno snižava LDL-h, non-HDL-h, Lp (a), TG i Apo B. U Americi je 2012. godine bila odobrena supkutana primena leka u dozi od 200 mg kod pacijenata sa HoFH. Zbog ozbiljnih neželjenih efekata, kao što su hepatotoksičnost i steatoza jetre, lek je povučen sa tržišta 2019. godine 46 .…”

Section: Mipomersenunclassified

Therapeutic approach in the treatment of dyslipidemia: Novelties and challenges

Lalić,

Rajković,

Popović

et al. 2024

Galenika Med J

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Cardiovascular diseases are the leading cause of morbidity and mortality worldwide. Dyslipidemia is a significant risk factor for the development of cardiovascular diseases, and lowering the level of serum lipids leads to a reduction in cardiovascular morbidity and mortality. The primary therapeutic target is LDL-cholesterol (c). Statin therapy is often not sufficient to achieve LDL-c target values, so it is necessary to combine them with other lipid-lowering drugs. However, after it was noticed that unwanted cardiovascular events occurred despite the achieved target values of LDL-c, attention was paid to the residual cardiovascular risk. Therefore, there was the development of new therapeutic strategies targeting triglyceriderich lipoproteins, lipoprotein (a), and apolipoproteins CIII and B. The results of early phases of randomized clinical studies indicated a significant effect of new drugs on reducing cardiovascular risk. This review article aims to present existing therapeutic options for the treatment of dyslipidemia, as well as new therapeutic agents and future perspectives for the treatment of these disorders.

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Mipomersen in Familial Hypercholesterolemia: An Update on Health-Related Quality of Life and Patient-Reported Outcomes

Cited by 34 publications

References 34 publications

Pharmacokinetics, pharmacodynamics, and safety of fesomersen, a novel antisense inhibitor of factor XI, in healthy Chinese, Japanese, and Caucasian volunteers

Pharmacokinetics, pharmacodynamics, and safety of fesomersen, a novel antisense inhibitor of factor XI, in healthy Chinese, Japanese, and Caucasian volunteers

VLDL Biogenesis and Secretion: It Takes a Village

Therapeutic approach in the treatment of dyslipidemia: Novelties and challenges

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