Pharmacokinetics, Pharmacodynamics, and Tolerability of Olpasiran in Healthy Japanese and Non-Japanese Participants: Results from a Phase I, Single-dose, Open-label Study

Sohn, Winnie; Winkle, Peter; Neutel, Joel M.; Wu, Yanyu; Jabari, Freeman; Terrio, Caitlin; Varrieur, Tracy; Wang, Jingying; Hellawell, Jennifer

doi:10.1016/j.clinthera.2022.07.008

Cited by 17 publications

(26 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…24,40 The other phase 1 trial was an open-label, parallel-design study conducted in 27 healthy volunteers of Japanese and non-Japanese origin aged 18–60 years with a BMI of 18–32 kg/m 2 . 25 In the FIH study, subjects were randomized into an experimental group that received a single test dose of olpasiran (ie, 3 mg, 9 mg, 75 mg, or 225 mg) and a control group that received a single matching dose of placebo. 24 In the aforementioned other phase 1 trial, non-Japanese participants received a single 75-mg dose of olpasiran while Japanese subjects were randomly assigned to receive a single dose of 3 mg, 9 mg, 75 mg, or 225 mg of the same drug.…”

Section: Resultsmentioning

confidence: 99%

“…24,25 The most common side effects were generally mild-to-moderate and included fatigue, headache, myalgia, oropharyngeal pain, nasopharyngitis, pruritus, rash, aphthous ulcer, sweating, upper respiratory tract infections, upper-airway cough syndrome, and vitreous floaters. 25 No serious side effects including death were reported. 24,25…”

Section: Resultsmentioning

confidence: 99%

“…In addition to the 2 abovementioned phase 1 studies of olpasiran with available findings, 24,25 the results of 3 ongoing open-label phase 1 studies with a single dose of olpasiran can be expected in the near future. 41–43 The first study (NCT04987320) aimed to investigate the pharmacokinetics, pharmacodynamics, safety, and tolerability of olpasiran in Chinese participants with elevated Lp(a) levels.…”

Section: Resultsmentioning

confidence: 99%

“…The results of the literature search and selection process are shown in Figure 2. A total of 12 publications [15][16][17][18][19][20][21][22][23][24][25][26] were included after the search in PubMed/MEDLINE, Web of Sciences, and Scopus, as well as 22 trial records, which were identified in ClinicalTrials.gov. Included publications and trial records referred to pelacarsen and its parent ASO IONIS2APO(a)Rx, olpasiran, SLN360 and LY3819469.…”

Section: Resultsmentioning

confidence: 99%

“…23 Pharmacokinetic parameters, efficacy, and safety of olpasiran were investigated in 2 phase 1 studies. 24,25 The first-in-human (FIH) study was designed as a randomized, double-blind, placebo-controlled trial conducted on patients with elevated plasma Lp(a) levels (NCT03626662). 24,40 The other phase 1 trial was an openlabel, parallel-design study conducted in 27 healthy volunteers of Japanese and non-Japanese origin aged 18-60 years with a BMI of 18-32 kg/m 2 .…”

Section: Olpasiranmentioning

confidence: 99%

See 4 more Smart Citations

Potential Novel RNA-Targeting Agents for Effective Lipoprotein(a) Lowering: A Systematic Assessment of the Evidence From Completed and Ongoing Developmental Clinical Trials

Milosavljević

Stefanović

Pejčić

2023

Journal of Cardiovascular Pharmacology

View full text Add to dashboard Cite

An increase in blood lipoprotein (a) [Lp(a)] levels, mostly genetically determined, has been identified as an independent risk factor of atherosclerotic cardiovascular disease. No drug has yet been approved that markedly lowers Lp(a) and thereby reduces residual cardiovascular risk. The aim of this article was to critically review the evidence from clinical development studies to date on the efficacy and safety of new RNA-based therapeutics for targeted lowering of Lp(a). PubMed/MEDLINE, Scopus, Web of Science, and ClinicalTrials.gov were searched without any language or date restriction up to November 5, 2022, and a total of 12 publications and 22 trial records were included. Several drugs were found that are currently in various stages of clinical development, such as the antisense oligonucleotide pelacarsen and the small interfering RNA molecule olpasiran and drugs coded as SLN360 and LY3819469. Among them, pelacarsen has progressed the most, currently reaching phase 3. All these drugs have so far shown satisfactory pharmacokinetic properties, consistently high and stable, dose-dependent efficacy in lowering Lp(a) even by more than 90%, with an acceptable safety profile in subjects with highly elevated Lp(a). In addition, reports of early clinical trials with pelacarsen imply a promising suppressive effect on key mechanisms of atherogenesis. Future research should focus on confirming these beneficial clinical effects in patients with lower average Lp(a) levels and clearly demonstrating the association between lowering Lp(a) and reducing adverse cardiovascular outcomes.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Olpasiranmentioning

confidence: 99%

See 3 more Smart Citations

Potential Novel RNA-Targeting Agents for Effective Lipoprotein(a) Lowering: A Systematic Assessment of the Evidence From Completed and Ongoing Developmental Clinical Trials

Milosavljević

Stefanović

Pejčić

2023

Journal of Cardiovascular Pharmacology

View full text Add to dashboard Cite

show abstract

Role of lipoprotein(a) in atherosclerotic cardiovascular disease: A review of current and emerging therapies

Alhomoud,

Talasaz,

Mehta

et al. 2023

Pharmacotherapy

View full text Add to dashboard Cite

Lipoprotein(a), or Lp(a), is structurally like low‐density lipoprotein (LDL) but differs in that it contains glycoprotein apolipoprotein(a) [apo(a)]. Due to its prothrombotic and proinflammatory properties, Lp(a) is an independent risk factor for atherosclerotic cardiovascular disease (ASCVD) and aortic valve stenosis. Lp(a) levels are genetically determined, and it is estimated that 20%–25% of the global population has an Lp(a) level ≥50 mg/dL (or ≥125 nmol/L). Diet and lifestyle interventions have little to no effect on Lp(a) levels. Lipoprotein apheresis is the only approved treatment for elevated Lp(a) but is time‐intensive for the patient and only modestly effective. Pharmacological approaches to reduce Lp(a) levels and its associated risks are of significant interest; however, currently available lipid‐lowering therapies have limited effectiveness in reducing Lp(a) levels. Although statins are first‐line agents to reduce LDL cholesterol levels, they modestly increase Lp(a) levels and have not been shown to change Lp(a)‐mediated ASCVD risk. Alirocumab, evolocumab, and inclisiran reduce Lp(a) levels by 20‐25%, yet the clinical implications of this reduction for Lp(a)‐mediated ASCVD risk are uncertain. Niacin also lowers Lp(a) levels; however, its effectiveness in mitigating Lp(a)‐mediated ASCVD risk remains unclear, and its side effects have limited its utilization. Recommendations for when to screen and how to manage individuals with elevated Lp(a) vary widely between national and international guidelines and scientific statements. Three investigational compounds targeting Lp(a), including small interfering RNA (siRNA) agents (olpasiran, SLN360) and an antisense oligonucleotide (pelacarsen), are in various stages of development. These compounds block the translation of messenger RNA (mRNA) into apo(a), a key structural component of Lp(a), thereby substantially reducing Lp(a) synthesis in the liver. The purpose of this review is to describe current recommendations for screening and managing elevated Lp(a), describe the effects of currently available lipid‐lowering therapies on Lp(a) levels, and provide insight into emerging therapies targeting Lp(a).

show abstract

Lipoprotein(a): Emerging insights and therapeutics

Kaur,

Abdelrahman,

Berman

et al. 2024

American Journal of Preventive Cardiology

View full text Add to dashboard Cite

Pharmacokinetics, Pharmacodynamics, and Tolerability of Olpasiran in Healthy Japanese and Non-Japanese Participants: Results from a Phase I, Single-dose, Open-label Study

Cited by 17 publications

References 27 publications

Potential Novel RNA-Targeting Agents for Effective Lipoprotein(a) Lowering: A Systematic Assessment of the Evidence From Completed and Ongoing Developmental Clinical Trials

Potential Novel RNA-Targeting Agents for Effective Lipoprotein(a) Lowering: A Systematic Assessment of the Evidence From Completed and Ongoing Developmental Clinical Trials

Role of lipoprotein(a) in atherosclerotic cardiovascular disease: A review of current and emerging therapies

Lipoprotein(a): Emerging insights and therapeutics

Contact Info

Product

Resources

About