zerlasiran (SLN360) / Silence Therap - LARVOL DELTA

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

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

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

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

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

Zerlasiran for the Treatment of Atherosclerotic Cardiovascular Disease. (PubMed, JAMA) - No abstract available

Journal • Atherosclerosis • Cardiovascular

Zerlasiran for the Treatment of Atherosclerotic Cardiovascular Disease-Reply. (PubMed, JAMA) - No abstract available

Journal • Atherosclerosis • Cardiovascular

Comprehensive evaluation of siRNA therapeutics on Lp(a): A network meta-analysis. (PubMed, Diabetes Obes Metab) - "Lp(a)-targeted siRNA agents have shown robust effectiveness in substantially reducing Lp(a) levels, including both percentage and absolute reductions, with moderate improvements in LDL-C and apo(B) concentrations. Non-Lp(a)-targeted siRNA agents also demonstrate modest reductions in Lp(a) levels. The safety profile is generally favourable, but zerlasiran and inclisiran may increase the incidence of injection-site reactions."

Journal • Retrospective data • Dyslipidemia • APOB

Silence Therapeutics Reports Full Year 2024 Financial Results and Provides Business Update (Businesswire) - "Zerlasiran for Cardiovascular Disease: Progressed core activities to ensure the zerlasiran program is Phase 3 ready in the first half of 2025....Partnering discussions for this program are ongoing; timing for Phase 3 initiation is dependent on partnership....Silence announced today that it will only initiate the zerlasiran Phase 3 CVOT study once a partner is secured. Following this announcement, Silence is extending its projected cash runway into 2027."

New P3 trial • Sales projection • Cardiovascular

Highlights of Cardiovascular Disease Prevention Studies Presented at the 2024 American Heart Association Scientific Sessions. (PubMed, Curr Atheroscler Rep) - "Included studies assessed effects of intensive blood pressure control in patients with type 2 diabetes (BPROAD); decision support system for physicians to optimize early lipid lowering therapies after acute coronary syndrome (ZODIAC); efficacy and safety of zerlasiran, a short interfering RNA targeting lipoprotein(a) (ALPACAR); efficacy and safety of muvalaplin an oral disrupter of the assembly of lipoprotein(a) particles (KRAKEN); safety and efficacy of obicetrapib in patients with heterozygous familial hypercholesterolemia (BROOKLYN); efficacy and safety of lerodalcibep, a third generation PCSK9 inhibitor in heterozygous familial hypercholesterolemia subjects (LIBerate-HeFH_OLE); personalized app-based coaching to improve physical activity in patients with HFpEF compared to standard care (MyoMobile); semaglutide to improve cardiovascular outcomes in patients with a history of coronary artery bypass surgery and overweight or obesity (the SELECT trial); efficacy and..."

Journal • Review • Acute Coronary Syndrome • Cardiovascular • Diabetes • Dyslipidemia • Familial Chylomicronemia Syndrome • Familial Hypercholesterolemia • Genetic Disorders • Heterozygous Familial Hypercholesterolemia • Metabolic Disorders • Obesity • Pancreatitis • Type 2 Diabetes Mellitus

Novel RNA-Based Therapies in the Management of Dyslipidemias. (PubMed, Int J Mol Sci) - "This article discusses the latest data from completed and ongoing trials on RNA therapies for dyslipidemia, including inclisiran, pelacarsen, olpasiran, zerlasiran, lepodisiran, volanesorsen, olezarsen, plozasiran, zodasiran, and solbinsiran. Each therapy targets specific molecules while also significantly impacting other lipid parameters. The promising results of these trials indicate potential improvements in lipid therapy and cardiovascular risk reduction, with ongoing studies expected to further refine the role of the novel RNA-based agents in effective lipid management."

Journal • Review • Atherosclerosis • Cardiovascular • Dyslipidemia • Metabolic Disorders • ANGPTL3

Zerlasiran An Investigational Short Interfering Ribonucleic Acid for Lowering Lipoproteina through Gene Silencing in Patients with Atherosclerotic Cardiovascular Disease (ASHP 2024) - No abstract available

Clinical • Atherosclerosis • Cardiovascular

Lp(a): A Rapidly Evolving Therapeutic Landscape. (PubMed, Curr Atheroscler Rep) - "Pelacarsen and olpasiran are two novel RNA-based injectable therapies which are being studied in ongoing phase 3 clinical trials, with the earliest of these to be concluded in 2025...Other candidate drugs, such as Lepodisiran, Zerlasiran, and Muvalaplin, are also in early-stage development. While there are presently no Lp(a)-lowering drugs available for routine clinical use, several promising candidates are currently under investigation. If these prove to be effective in randomized clinical trials, they will expand the cardiovascular care armamentarium and will allow clinicians to treat a presently unmitigated cardiovascular risk factor."

Clinical • Journal • Review • Atherosclerosis • Cardiovascular • Coronary Artery Disease • Dyslipidemia

ALPACAR Phase 2 Trial of Zerlasiran: Multiple doses of a Small-Interfering RNA Targeting Lipoprotein(a) with 60 weeks Folow Up. (AHA 2024) - "There were 20 serious adverse events in 17 patients, all unrelated to study drug.CONCLUSIONS. Zerlasiran was well tolerated and produced greater than 80% reductions in time-averaged Lp(a) concentrations and 25.1 to 31.9% time-averaged reduction in LDL-C during 36 weeks of treatment."

Late-breaking abstract • P2 data • Atherosclerosis • Cardiovascular • Dyslipidemia

Zerlasiran-A Small-Interfering RNA Targeting Lipoprotein(a): A Phase 2 Randomized Clinical Trial. (PubMed, JAMA) - P2 | "Zerlasiran was well-tolerated and reduced time-averaged lipoprotein(a) concentration by more than 80% during 36 weeks of treatment in patients with ASCVD. ClinicalTrials.gov Identifier: NCT05537571."

Clinical • Journal • P2 data • Atherosclerosis • Cardiovascular • Dyslipidemia • Pain

RNA interference therapy in cardiology: will new targets improve therapeutic goals? (PubMed, Drugs Context) - "Patisiran, the first FDA-approved siRNA medication, targets hereditary transthyretin amyloidosis with polyneuropathy. Givosiran, lumasiran and nedosiran further expand siRNA applications in treating rare genetic diseases, demonstrating positive outcomes. In cardiology, inclisiran, approved for hypercholesterolaemia, showcases sustained reductions in LDL cholesterol levels...Lipoprotein(a), an independent risk factor for atherosclerotic cardiovascular disease, has become a focus of siRNA therapies, precipitating the development of specific siRNA drugs like olpasiran, zerlasiran and lepodisiran, with promising reductions in lipoprotein(a) levels...Zodasiran and plozasiran address potential risk factors for cardiovascular diseases, targeting triglyceride-rich lipoproteins. Zilebesiran, which targets hepatic angiotensinogen mRNA, has demonstrated a dose-related reduction in serum angiotensinogen levels, thereby lowering blood pressure in patients with systemic arterial..."

Journal • Review • Amyloidosis • Atherosclerosis • Cardiac Amyloidosis • Cardiovascular • Dyslipidemia • Genetic Disorders • Hypertension • Pain • Pulmonary Arterial Hypertension

Evaluate SLN360 in Participants With Elevated Lipoprotein(a) at High Risk of Atherosclerotic Cardiovascular Disease Events (clinicaltrials.gov) - P2 | N=180 | Completed | Sponsor: Silence Therapeutics plc | Active, not recruiting ➔ Completed

Trial completion • Atherosclerosis • Cardiovascular • Dyslipidemia

Lipoprotein (a) and lipid-lowering treatment from the perspective of a cardiac surgeon. An impact on the prognosis in patients with aortic valve replacement and after heart transplantation. (PubMed, Int J Cardiol Cardiovasc Risk Prev) - "There is still no targeted therapy for Lp(a), however, drugs such as pelacarsen, olpasiran, zerlasiran, lepodisiran and muvalaplin are in clinical trials and have been shown to be effective in significantly reducing Lp(a) levels. Therefore, the assessment of Lp(a) concentration in these patients will allow for a more accurate stratification of their cardiovascular risk, and the possibility of lowering Lp(a) will allow for the optimization of this risk. In this article, we summarized the most important information regarding the role of Lp(a) and lipid-lowering treatment in patients after AVR and HTx."

Journal • Cardiovascular • Transplantation

Therapeutic Potential of Lipoprotein(a) Inhibitors. (PubMed, Drugs) - "Early studies of antisense oligonucleotides (e.g., mipomersen, pelacarsen), RNA interference (e.g., olpasiran, zerlasiran, lepodisiran) and small molecule inhibitors (e.g., muvalaplin) have demonstrated effective Lp(a) lowering and good tolerability. These agents are moving forward in clinical development, in order to determine whether Lp(a) lowering reduces cardiovascular risk. The results of these studies have the potential to transform our approach to the prevention of cardiovascular disease."

Journal • Atherosclerosis • Cardiovascular • Dyslipidemia

Elevated Lipoprotein(a) Levels: A Crucial Determinant of Cardiovascular Disease Risk and Target for Emerging Therapies. (PubMed, Curr Probl Cardiol) - "Newly emerging therapies, including pelacarsen, zerlasiran, olpasiran, muvalaplin, and lepodisiran, show promise in significantly lowering Lp(a) levels, potentially transforming the management of cardiovascular disease. However, further research is essential to assess these novel therapies' long-term efficacy and safety, heralding a new era in cardiovascular disease prevention and treatment and providing hope for at-risk patients."

Journal • Review • Atherosclerosis • Cardiovascular • Dyslipidemia • Hematological Disorders • Inflammation • Thrombosis

Single Ascending and Multiple-Dose Trial of Zerlasiran, a Short Interfering RNA Targeting Lipoprotein(a): A Randomized Clinical Trial. (PubMed, JAMA) - P1 | "Zerlasiran was well tolerated and reduced lipoprotein(a) concentrations with infrequent administration. ClinicalTrials.gov Identifier: NCT04606602."

Clinical • Journal • Atherosclerosis • Cardiovascular • Dyslipidemia

Silence Therapeutics Achieves $10 Million Milestone Payment from AstraZeneca Collaboration Following the Initiation of Phase 1 Trial (Businesswire) - "Silence Therapeutics plc...today announced that the initiation by AstraZeneca of a phase 1 clinical trial of the first product candidate under its siRNA (short interfering RNA) collaboration, has triggered a $10.0 million milestone payment to Silence...'In addition to this great achievement under our collaboration with AstraZeneca, we are also pleased with the continued advancement of our proprietary pipeline with encouraging clinical data now emerging from our zerlasiran program in high Lp(a) and divesiran program in polycythemia vera.'"

Clinical • Licensing / partnership • Cardiovascular • Hematological Malignancies • Myeloproliferative Neoplasm • Oncology • Polycythemia Vera

Targeting Lipoprotein(a): Can RNA Therapeutics Provide the Next Step in the Prevention of Cardiovascular Disease? (PubMed, Cardiol Ther) - "Promising treatment approaches targeting apo(a) expression include RNA-based drugs such as pelacarsen, olpasiran, SLN360, and lepodisiran, which are currently in clinical trials. In this comprehensive review, we provide a detailed overview of RNA-based therapeutic approaches and discuss the recent advances and challenges of RNA therapeutics specifically designed to reduce Lp(a) levels and thus the risk of cardiovascular disease."

Journal • Review • Cardiovascular • Congestive Heart Failure • Coronary Artery Disease • Dyslipidemia • Heart Failure • APOB