olpasiran (AMG 890) / Amgen, Arrowhead, Royalty - LARVOL DELTA

Clinical Response to Elevated Lipoprotein(a): Practical Approach for Risk Management in the Absence of Targeted Therapies. (PubMed, Semin Thromb Hemost) - "Statins, ezetimibe, bempedoic acid and lifestyle interventions have little or no effect on Lp(a). Statins may modestly raise levels, niacin is now contraindicated as it has not been shown to reduce cardiovascular or all-cause mortality, while PCSK9 (Proprotein Convertase Subtilisin/Kexin type 9) inhibitors and inclisiran reduce Lp(a) concentrations by ~20-30%, though this effect remains secondary to their LDL-C lowering effect...Future promise lies in RNA-based therapies, including antisense oligonucleotides (pelacarsen) and small-interfering RNAs (olpasiran, lepodisiran, SLN360), which achieve 80-95% sustained Lp(a) reductions...High or extreme elevations, especially with ASCVD, mandate aggressive LDL-C lowering, optimization of modifiable risk factors, family cascade screening, and apheresis or referral to RNA-therapy trials in select cases. Thus, while therapeutic options remain limited, systematic measurement and risk stratification are ethically justified to prepare..."

Journal • Atherosclerosis • Cardiovascular • Dyslipidemia

The Emerging Lipid Risk: Lipoprotein(a). (PubMed, Korean Circ J) - "Trials on new therapeutics targeting Lp(a) RNA, including antisense oligonucleotide (e.g., pelacarsen), siRNAs (e.g., olpasiran, lepodisiran, and zerlasiran), and small molecules (e.g., muvalaplin), are under way. Depending on the study or dose, these agents lowered Lp(a) levels by 80-100% compared with the control; however, results of clinical outcomes have yet to be reported."

Journal • Review • Atherosclerosis • Cardiovascular • Coronary Artery Disease • Dyslipidemia • Preventive care

Lipoprotein(a) - treatments in development. (PubMed, Expert Opin Pharmacother) - "The N-acetylgalactosamine (GalNAc)-conjugated antisense oligonucleotide (ASO) pelacarsen and the small-interfering RNA (siRNA) agents olpasiran, lepodisiran and zerlasiran have all been shown to be safe and effective in lowering Lp(a) levels between 80% and almost 100%...Muvalaplin is a small molecule given orally once daily and reduces Lp(a) by up to 65%. It is also being assessed in a cardiovascular outcome study. It will be essential to identify what baseline level of Lp(a) is needed and what degree of Lp(a) lowering is required to produce a cardiovascular benefit and whether aggressive lowering of Lp(a) has any adverse effects."

Journal • Review • Cardiovascular

Lipoprotein(a) in Cardiovascular Diseases and Emerging Therapeutic Strategies. (PubMed, Cardiovasc Drugs Ther) - "As novel therapies advance and clinical guidelines evolve, Lp(a) is emerging as a central determinant in personalized cardiovascular care. The increasing emphasis on Lp(a) testing underscores its importance in risk stratification and future therapeutic decisionmaking."

Journal • Review • Atherosclerosis • Cardiovascular • Peripheral Arterial Disease

Small-Interfering RNA Olpasiran and Apolipoprotein B Particles. (PubMed, JAMA Cardiol) - No abstract available

Journal • APOB

LPA-Targeted siRNAs Lower Lp(a) by Over 90%: A Meta-Analysis of Olpasiran, Lepodisiran, and Zerlasiran (AHA 2025) - "siRNA therapeutics targeting LPA mRNA demonstrate substantial efficacy, lowering Lp(a) levels by over 90% with concurrent reductions in ApoB and LDL-C. Ongoing phase 3 trials will be pivotal in further characterizing their safety profile and determining the extent to which these promising lipid changes translate into cardiovascular risk reduction."

Retrospective data • Atherosclerosis • Cardiovascular • Dyslipidemia • APOB

Efficacy of Olpasiran by Apolipoprotein(a) Isoform Size: Insights from the OCEAN(a)-DOSE Trial (AHA 2025) - "In patients with ASCVD and elevated Lp(a), olpasiran reduces Lp(a) irrespective of apo(a) isoform size and appears to affect both isoforms equally."

Clinical • Atherosclerosis • Cardiovascular

Olpasiran Outperforms Other Subcutaneous Lipoprotein(a)-Lowering Agents in Efficacy and Safety: A Network Meta-Analysis of Randomized Controlled Trials (AHA 2025) - "Compared to placebo, olpasiran showed the largest reduction in Lp(a) (MD: –87.72%; 95% CI: –113.78 to –61.66), followed by zerlasiran (–66.68%), lepodisiran (–54.61%), and pelacarsen (–54.15%). Among Lp(a)-targeted therapies, olpasiran showed the largest Lp(a), LDL-C, ApoB, and ACM lowering effects, ranking better than other drugs. Olpasiran and lepodisiran ranked better for reducing safety outcomes than other drugs."

Retrospective data • APOB

Changes in Lipoprotein(a) and Oxidized Phospholipids Are Associated with Myocardial Inflammation but Not Systemic Inflammatory Markers Following an Acute Myocardial Infarction (AHA 2025) - "In the OCEAN(a) DOSE trial olpasiran reduced Lp(a) and OxPL-apoB but not hs-CRP or IL-6, markers of systemic inflammation...We examined the associations between the changes of Lp(a), OxPL-apoB, hs-CRP, and IL-6, and the changes of local myocardial inflammation from hospitalization to 30 days in patients with an acute myocardial infarction (MI).Research Objective: To determine the association of changes in Lp(a), OxPL-apoB, hsCRP, and IL-6 with the changes in local myocardial inflammation following an MI. Fifty-five patients from the EVACS I and II trials with an acute MI were randomized to evolocumab, a PCSK9 inhibitor known to reduce Lp(a) levels or placebo and underwent 18F-FDG PET imaging during hospitalization and at 30 days... Changes in myocardial inflammation after an acute MI were associated with changes in Lp(a) and OxPL-apoB but not with indices of systemic inflammation. These findings support a pathophysiologic role for Lp(a)-associated OxPLs in myocardial..."

Cardiovascular • Inflammation • Myocardial Infarction • APOB • CRP • IL6

AMGEN'S LANDMARK PHASE 3 REPATHA DATA TO BE PRESENTED AS LATE BREAKER AT THE AMERICAN HEART ASSOCIATION SCIENTIFIC SESSIONS 2025 (Amgen Press Release)

Clinical data • Atherosclerosis • Cardiovascular • Obesity

OCEAN(a)-PreEvent - Olpasiran Trials of Cardiovascular Events And LipoproteiN(a) Reduction to Prevent First Major Cardiovascular Events (clinicaltrials.gov) - P3 | N=11000 | Recruiting | Sponsor: Amgen | Trial completion date: Mar 2031 ➔ Oct 2031 | Trial primary completion date: Mar 2031 ➔ Oct 2031

Trial completion date • Trial primary completion date • Cardiovascular

OCEAN(a)-PreEvent - Olpasiran Trials of Cardiovascular Events And LipoproteiN(a) Reduction to Prevent First Major Cardiovascular Events (clinicaltrials.gov) - P3 | N=11000 | Recruiting | Sponsor: Amgen | Trial completion date: Oct 2031 ➔ Mar 2031 | Trial primary completion date: Oct 2031 ➔ Mar 2031

Trial completion date • Trial primary completion date • Cardiovascular

Efficacy of siRNA in lowering lipoprotein(a) and LDL-cholesterol: a meta-analysis of randomized controlled trials (ESC-WCC 2025) - "The doses are: Lepodisiran (Q1: 4mg-12mg-32mg; Q2: 96mg; Q3: 304mg; Q4: 608mg), Olpasiran (Q1: 10mg; Q2: 75mg; Q3: 225mg), Zerlasiran (Q1: 30mg; Q2: 100mg; Q3: 200mg-300mg; Q4: 450mg-600mg), and Zodasiran (Q1: 50mg; Q2: 100mg; Q3: 200 mg). The findings of this meta-analysis demonstrate that siRNA treatment significantly reduces Lp(a) levels in a dose-dependent manner, with higher doses achieving greater efficacy. Additionally, siRNA also lowers LDL-C levels, regardless of dose escalation. However, phase III clinical trials are needed to confirm the safety and efficacy of this therapeutic approach and to establish its correlation with reduced cardiovascular risk."

Retrospective data • Atherosclerosis • Cardiovascular • Dyslipidemia

OCEAN(a)-PreEvent - Olpasiran Trials of Cardiovascular Events And LipoproteiN(a) Reduction to Prevent First Major Cardiovascular Events (clinicaltrials.gov) - P3 | N=11000 | Recruiting | Sponsor: Amgen

New P3 trial • Cardiovascular

Olpasiran Expanded Access Program (clinicaltrials.gov) - P=N/A | N=0 | Available | Sponsor: Amgen

New trial

Lipoprotein (a): A new target for pharmacological research and an option for treatment. (PubMed, Eur J Intern Med) - "Novel RNA-based therapies, including antisense oligonucleotides (pelacarsen) and small interfering RNAs (olpasiran, lepodisiran, zerlasiran)-have shown the potential to reduce Lp(a) levels by >80 %. The small oral molecule muvalaplin also shows promise in inhibiting Lp(a) formation...As new therapeutic options are developed that specifically target Lp(a), the inclusion of Lp(a) in cardiovascular risk assessment could improve stratification and lead to targeted interventions, particularly in high-risk populations. The growing body of genetic, epidemiological and clinical evidence makes Lp(a) a critical target in cardiovascular research and therapy."

Journal • Review • Atherosclerosis • Cardiovascular • Congestive Heart Failure • Dyslipidemia • Familial Hypercholesterolemia • Heart Failure • Peripheral Arterial Disease

Emerging pharmacological strategies in lipoprotein(a) reduction. (PubMed, Proc (Bayl Univ Med Cent)) - P3 | "The three large, multicenter phase 3 outcome trials evaluating clinical cardiovascular disease endpoints of major adverse cardiac event (MACE) are Lp(a)HORIZON (NCT04023552), OCEAN(a) (NCT05581303), and ACCLAIM-Lpa(a) (NCT06292013), which investigate pelacarsen, olpasiran, and lepodisiran, respectively. Other phase 2 and phase 3 trials are also under way. Results from upcoming trials will inform us whether Lp(a) reductions translate to improved cardiovascular clinical outcomes."

Journal • Atherosclerosis • Cardiovascular • Dyslipidemia

Advances in RNA-Based Therapies Targeted at Lipoprotein(a): Olpasiran in the Management of Atherosclerotic Cardiovascular Disease. (PubMed, Cardiol Rev) - "Olpasiran also has the potential to be a cost-effective treatment due to the infrequent dosing needed to achieve a high degree of Lp(a) reduction. Other similar nucleic acid therapeutic agents, such as pelacarsen, zerlasiran, and lepodisiran, have also shown efficacy in reducing Lp(a) levels in early trials, creating an exciting avenue for cardiovascular prevention in the coming decade."

Journal • Atherosclerosis • Cardiovascular

An Open-Label, Single-Dose Study to Evaluate the Pharmacokinetics, Pharmacodynamics, Safety, and Tolerability of Olpasiran in Chinese Participants With Elevated Serum Lipoprotein(a). (PubMed, Clin Ther) - "Olpasiran administration (75 and 225 mg) was safe and well-tolerated in Chinese participants, and olpasiran PK and Lp(a) responses are generally consistent with those observed in East Asian/non-East Asian participants. Dose adjustments of olpasiran based on ethnicity are therefore not warranted, and work investigating the effects of olpasiran treatment on long-term cardiovascular risk in East Asian populations should continue."

Journal • PK/PD data • Cardiovascular

Comparative Efficacy of Olpasiran and Zerlasiran in Reducing Lipoprotein(a) Levels: A Network Meta-Analysis of Clinical Trials (ENDO 2025) - "Both Olpasiran and Zerlasiran are highly effective in reducing Lp(a) levels, with Olpasiran showing a numerically greater reduction. These findings underscore the therapeutic potential of RNA-based agents in addressing elevated Lp(a), a critical modifiable risk factor for cardiovascular diseases."

Retrospective data • Cardiovascular • Congestive Heart Failure • Coronary Artery Disease • Heart Failure • Ischemic stroke • APOB

Cardiovascular risk management beyond statins: review of new therapies available in Italy. (PubMed, Egypt Heart J) - "This review underscores the evolving landscape of lipid-lowering therapies, with emphasis on agents acting through novel mechanisms beyond statin pathways. Bempedoic acid, by inhibiting ACLY and increasing LDL receptor expression, represents a safe and effective option for reducing LDL-C, especially in statin-intolerant individuals. PCSK9 inhibitors further expand therapeutic options by augmenting LDL receptor recycling and clearance. The integration of these agents into clinical practice may help mitigate residual cardiovascular risk and personalize treatment strategies in dyslipidemia management."

Journal • Review • Atherosclerosis • Cardiovascular • Dyslipidemia • Metabolic Disorders • APOA1

Amgen launches Korean phase 3 trial for heart drug targeting high lipoprotein (Korea Biomedical Review) - "Korea’s Ministry of Food and Drug Safety has approved a phase 3 trial of Amgen’s siRNA therapy olpasiran, clearing the way for a study in 179 patients with elevated lipoprotein(a), a cholesterol variant linked to early heart attacks and strokes...The new trial builds on Amgen’s earlier phase 3 study in Korea, launched in April 2023, which focuses on patients with existing atherosclerotic cardiovascular disease. That study is expected to conclude in January 2027."

Trial completion date • Trial status • Cardiovascular • Dyslipidemia

Lp(a)-Lowering Agents in Development: A New Era in Tackling the Burden of Cardiovascular Risk? (PubMed, Pharmaceuticals (Basel)) - "Such drugs include pelacarsen (an injectable ASO) and olpasiran, zerlasiran, and lepodisiran (injectable siRNA agents). Muvalaplin represents another therapeutic option to lower Lp(a) levels, since it is an oral selective small molecule inhibitor of Lp(a) formation, thus potentially exerting certain advantages in terms of its clinical use...The phase 3 CV trial outcomes are ongoing for some of these agents (i.e., pelacarsen, olpasiran, and lepodisiran) and are briefly mentioned. Overall, there is an urgent need for evidence-based guidelines on Lp(a) reduction in daily clinical practice, following the results of the phase 3 CV trials, as well as for establishing the ideal Lp(a) quantification method (i.e., using an apo(a) isoform-independent assay with appropriate calibrators, reporting the Lp(a) level in molar units)."

Journal • Review • Atherosclerosis • Cardiovascular • Coronary Artery Disease • Heart Failure

Small Interfering RNA (siRNA) in Dyslipidemia: A Systematic Review on Safety and Efficacy of siRNA. (PubMed, J Exp Pharmacol) - "Inclisiran led to a notable 44.09% reduction in LDL and 37.5% in apolipoprotein levels among individuals with hypercholesterolemia. In hyperlipoproteinemia(a), therapies like Lepodisiran and Olpasiran achieved a 75.69% drop in apolipoproteins and 16.25% in LDL. For hypertriglyceridemia, agents such as ARO-APOC3 and Plozasiran showed over 50% reductions in both VLDL and triglycerides...In conclusion, the benefits of siRNA therapy in dyslipidemia management appear to outweigh its potential drawbacks, demonstrating promising efficacy and safety profiles. However, further research is necessary to fully understand its long-term effects and optimize its therapeutic potential."

Journal • Review • Back Pain • Cardiovascular • Diabetes • Dyslipidemia • Hypertension • Hypertriglyceridemia • Infectious Disease • Metabolic Disorders • Mixed Hyperlipidemia • Musculoskeletal Pain • Pain

Small interfering RNA effect on lipoprotein(a): a systematic review. (PubMed, Egypt Heart J) - "siRNA therapies show promise in effectively lowering Lp(a) levels, with minimal adverse effects. However, further research is required to establish their long-term safety and efficacy."

Journal • Review • Cardiovascular • Coronary Artery Disease • Dyslipidemia • APOB