Praluent (alirocumab) / Sanofi, Regeneron - LARVOL DELTA

Lerodalcibep-liga as an Injectable Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9)-Targeted Therapy for Patients With Hypercholesterolemia. (PubMed, Ann Pharmacother) - "Lerodalcibep-liga is an additional potent injectable PCSK9-directed treatment for adults requiring substantial LDL-C reduction, including those with HeFH. However, alirocumab or evolocumab may remain preferable when demonstrated cardiovascular event reduction is a major consideration in treatment selection."

Journal • Review • Atherosclerosis • Cardiovascular • Dyslipidemia • Familial Hypercholesterolemia • Genetic Disorders • Heterozygous Familial Hypercholesterolemia • Metabolic Disorders • APOB

PCSK9 Inhibitors Added to Moderate/High-Intensity Statin Therapy Are Associated With Improved Liver-Related Outcomes in Patients With Metabolic Dysfunction-Associated Steatotic Liver Disease (ACG 2026) - "We compared patients who initiated a PCSK9 inhibitor (alirocumab, evolocumab, or inclisiran) at least 3 months after MASLD diagnosis (n=10,940) versus those on M/HI statins alone (n=604,717). After PSM, 10,216 patients per group were identified (Table 1). Median follow-up was 516 vs. 485 days."

Clinical • CNS Disorders • Dyslipidemia • Familial Hypercholesterolemia • Fibrosis • Gastroenterology • Genetic Disorders • Hepatic Encephalopathy • Hepatocellular Cancer • Hepatology • Immunology • Metabolic Disorders • Metabolic Dysfunction-Associated Steatotic Liver Disease • Solid Tumor

Comment on "Lipoprotein(a) reduction with inclisiran, alirocumab, evolocumab, enlicitide, and lerodalcibep: A systematic review and meta-analysis of randomized controlled trials". (PubMed, Int J Cardiol Cardiovasc Risk Prev) - No abstract available

Journal • Retrospective data

Evolocumab for high cardiovascular risk patients without previous stroke: a network meta-analysis of randomized controlled trials (ESC 2026) - "Purpose: To investigate the efficacy and safety of non-statin treatments—including evolocumab, alirocumab, enlicitide, inclisiran, evinacumab, omega-3 fatty acids, and ezetimibe—in high CV risk patients without previous stroke. Evolocumab had the potential to be the first-line non-statin option for high CV risk patients without previous stroke due to its efficacy in reducing MACE, CV mortality, LDL-C, and Lp(a)."

Retrospective data • Cardiovascular • Dyslipidemia • Myocardial Infarction

A retrospective study of disproportionality analysis signals between proprotein convertase subtilisin/kexin 9 inhibitor use and respiratory, thoracic, and mediastinal disorders. (PubMed, Medicine (Baltimore)) - "The median time to onset for adverse event reports was 7.5 days (interquartile range = 0.5-77.5 days); the median time to onset for reports related to alirocumab was 14.5 days (interquartile range = 1.5-100.5 days), while for evolocumab it was only 6.5 days (interquartile range = 0.5-70.5 days). Among these, rhinorrhea, cough, oropharyngeal pain, nasal congestion, and dysphonia were the most frequently reported preferred terms (PTs). The results of this study indicate the presence of a disproportionate signal of RTMD adverse events associated with PCSK9i in the FAERS database; however, this merely suggests that such events warrant further attention in reports related to PCSK9i and does not establish a causal relationship between the 2."

Journal • Retrospective data • Cough • Dysphonia • Pain • Respiratory Diseases

Contemporary non-statin therapies for dyslipidemia management: achieving current lipid targets. (PubMed, Front Med (Lausanne)) - "Third evidence indicates that non-statin therapies-including ezetimibe, bempedoic acid, PCSK9 inhibitors (evolocumab and alirocumab), and inclisiran-provide substantial LDL-C reductions and reduce cardiovascular events...Additionally, the fixed-dose combination of bempedoic acid and ezetimibe produces an approximately 36.2% reduction in LDL-C in high-risk patients...Furthermore, inflammation (measured by hsCRP) provides complementary prognostic information beyond LDL-C. This expert position paper proposes practical algorithms for a precision medicine approach in Latin America, matching treatment intensity to individual risk profiles for the primary and secondary prevention of atherosclerotic cardiovascular disease."

Journal • Review • Atherosclerosis • Cardiovascular • Dyslipidemia • Inflammation • Metabolic Disorders • CRP

Real-world comparative outcomes of evolocumab versus high-intensity statin for primary prevention (ESC 2026) - "Cohorts required initiation of either high-intensity statin therapy (atorvastatin 40–80 mg or rosuvastatin 20–40 mg) or evolocumab; each cohort excluded use of the comparator lipid-lowering agent and alirocumab. In this large propensity score–matched analysis of primary prevention patients with ASCVD risk factors, evolocumab was associated with significantly lower all-cause mortality, acute heart failure, and hospitalization compared with high-intensity statin therapy. However, evolocumab users demonstrated higher rates of acute MI and persistent LDL-C elevation. These findings suggest potential complementary roles for PCSK9 inhibitors in primary prevention but warrant prospective validation."

Clinical • Real-world • Real-world evidence • Atherosclerosis • Cardiovascular • Congestive Heart Failure • Dyslipidemia • Heart Failure • Myocardial Infarction

Alirocumab and cardiovascular outcomes in patients without a prior ischemic event (ESC 2026) - "VESALIUS-CV recently showed that evolocumab lowers cardiovascular event rates in patients without prior myocardial infarction (MI) or stroke...Use of lipid-lowering therapy, including statin+ ezetimibe combination, was high in both groups (Table)... In this population-based cohort of patients with ASCVD without prior acute ischemic events, alirocumab was associated with lower 4-year risk of all-cause death, MI, or ischemic stroke, supporting the clinical value of alirocumab in these patients and complementing recent randomized trial evidence."

Clinical • Acute Coronary Syndrome • Atherosclerosis • Cardiovascular • Ischemic stroke • Myocardial Infarction

Efficacy of PCSK9 inhibitors in patients with peripheral artery disease: insights from the AT-TARGET-IT Registry (ESC 2026) - "LDL-cholesterol (LDL-C) lowering improves outcomes in PAD, and randomized evidence supports the use of proprotein convertase subtilisin/kexin type-9 inhibitors (PCSK9i) on top of statin ± ezetimibe therapy...The purpose of this subanalysis was to investigate efficacy and safety of PCSK9i in patients with PAD. Patients with PAD initiating evolocumab or alirocumab (75, 150 or 300 mg), according to ESC/EAS Guidelines indications and national reimbursement criteria, were enrolled in the AT-TARGET-IT registry... A total of 124 patients with PAD were enrolled in the AT-TARGET-IT registry (61.3% male, median age 59 years), of whom 118 had at least one follow-up recorded. Of these patients, 61.3% had hypertension, 17.7% had type 2 diabetes mellitus, and 21.8% had a previous history of lower limb revascularization. Baseline median ankle brachial index (ABI) was 0.8 (IQR 0.7-0.9), and most patients had symptomatic PAD, predominantly Fontaine stage IIa (30.6%) and IIb (48.4%),..."

Clinical • Cardiovascular • Hypertension • Peripheral Arterial Disease

Comparative Cardiovascular Outcomes Across PCSK9-Targeted Therapies: A Real-World Matched Cohort Analysis of Inclisiran, Alirocumab, and Evolocumab (AHA 2026) - "Abstract is embargoed at this time."

Clinical • Real-world • Real-world evidence • Cardiovascular

PCSK9 Inhibitors in Primary Cardiovascular Prevention: A Multi-Cohort Comparative Effectiveness Study of Evolocumab and Alirocumab versus Oral Dual Lipid-Lowering Therapy Using Real-World Electronic Health Records (AHA 2026) - "Abstract is embargoed at this time."

Clinical • HEOR • Real-world • Real-world evidence • Cardiovascular

Comparative LDL-C Reduction and Cardiovascular Outcomes With PCSK9-Pathway Therapies: A Systemic Review and Network Meta-Analysis (ESC 2026) - "Injection-site reactions were lowest with lerodalcibep and highest with inclisiran. SUCRA rankings for injection-site reactions favored lerodalcibep, followed by alirocumab/evolocumab, with inclisiran ranking lowest.ConclusionPCSK9-pathway therapies significantly reduce LDL-C, with lerodalcibep demonstrating the greatest lipid-lowering effect, while only evolocumab and alirocumab show definitive MACE reduction; overall safety profiles were comparable across agents."

Retrospective data • Review • Cardiovascular • Dyslipidemia

Gender-related differences in efficacy, safety and adherence of PCSK9 inhibitors in real-world clinical practice: insights from the AT-TARGET-IT Registry (ESC 2026) - "The purpose of this subanalysis was to investigate gender-related differences in efficacy, safety, adherence, and persistence of PCSK9i in a large real-world registry. A sex-stratified analysis of patients initiating evolocumab or alirocumab (75, 150 or 300 mg), according to ESC/EAS Guidelines indications and national reimbursement criteria, was performed. A total of 2540 patients, with at least one follow-up recorded, were included in this analysis, of whom 791 (31.1%) were women. Compared with men, women were slightly older (mean age 62.7±9.5 vs 60.1±10.3 years; p<0.001) and had higher median baseline LDL-C levels (146 vs 134 mg/dL; p<0.001). After a median follow-up of 17.1 months, significantly lower LDL-C percentage reduction was observed in women compared to men (61.2% vs 66.7%, p<0.001), while absolute LDL-C reduction was similar between genders (89 mg/dL in women vs 87.4 mg/dL in men; p=0471)."

Adherence • Clinical • Real-world • Real-world evidence • Cardiovascular

Management of Lorlatinib-Induced Hyperlipidemia With PCSK9 Inhibitors: A Case Series (IASLC-WCLC 2026) - "Case Description : Case 1: A 66-year-old male on second-line lorlatinib 75 mg daily had normal baseline lipid levels but progressed to mixed hyperlipidemia refractory to pravastatin 40 mg daily, and partially improved on rosuvastatin 40 mg daily and ezetimibe 10 mg daily. After prolonged lifestyle modification attempts over four and a half years, alirocumab 75 mg/mL every 2 weeks (Q2W) was added, achieving lipid control (Figure 1)...She transitioned to evolocumab 140 mg/mL Q2W with bempedoic acid 180 mg daily with mild improvement...Conclusions : These four case reports illustrate the benefit of addition of a PSCK9i in treatment-related, refractory hyperlipidemia. PSCK9i are effective in lowering total cholesterol and LDL in patients with lorlatinib-induced hyperlipidemia and may be considered early in severe and statin-refractory cases."

Clinical • Dyslipidemia • Hypertension • Immunology • Lung Cancer • Mixed Hyperlipidemia • Musculoskeletal Pain • Non Small Cell Lung Cancer • Solid Tumor • ALK

OPTIMUS-EPIC: Impact of Alirocumab on Cardiovascular Events in Participants With Atherosclerotic Cardiovascular Disease But Without Prior Ischemic Events (clinicaltrials.gov) - P=N/A | N=4006 | Completed | Sponsor: Sanofi | Active, not recruiting ➔ Completed

Trial completion • Atherosclerosis • Cardiovascular • Myocardial Infarction

PCSK9 inhibition attenuates alcohol-induced cardiovascular dysfunction and links hepatic lipid accumulation to impaired myocardial contractile reserve. (PubMed, Geroscience) - "Male Sprague-Dawley rats were assigned to pair-fed control or 35% ethanol liquid diet groups and treated weekly with subcutaneous alirocumab, 50 mg/kg, or vehicle for 6 weeks...Liver triglyceride content correlated inversely with ESPVR slope and PRSW. These findings identify PCSK9 as a potential therapeutic target for alcohol-related cardiovascular dysfunction and associated cardiac-hepatic injury."

Journal • Cardiovascular • Fibrosis • Hepatology • Immunology • Inflammation • Liver Failure • NOX4 • PLIN2 • TNFA

Association of lipoprotein(a) levels with risk of serious bleeding : findings from the ODYSSEY OUTCOMES trial (ESC 2026) - "The trial population with recent acute coronary syndromes (ACS) was opportune due to high prevalent use of potent antiplatelet therapy. ODYSSEY OUTCOMES enrolled 18924 patients 1-12 months post ACS and elevated atherogenic lipoproteins despite optimized statin therapy, randomized to PCSK9 inhibitor alirocumab (ALI) or placebo, and followed for median 2.8 years... In this post hoc analysis, there was no evidence of an inverse association of Lp(a) levels with serious bleeding or with cerebral hemorrhage. There was no indication that treatment with ALI or decreases in Lp(a) on ALI increased bleeding; to the contrary, decreases in Lp(a) on ALI were associated with decreased bleeding risk, a finding that might be related to ALI prevention of ischemic events and therefore intensity or duration of antiplatelet therapy. These reassuring findings require confirmation in ongoing randomized trials evaluating targeted Lp(a)-lowering agents."

Acute Coronary Syndrome • Cardiovascular • Hypertension

Add-On PCSK9 Inhibitor Therapy for Acute Stroke Attributable to Intracranial Atherosclerosis: A Randomized Clinical Trial. (PubMed, J Am Heart Assoc) - P2 | "In patients with symptomatic intracranial atherosclerotic stenosis, adjunctive PCSK9i therapy significantly reduced intracranial stenosis and improved low-density lipoprotein cholesterol control over 6 months."

Clinical • Journal • Atherosclerosis • Cardiovascular • Dyslipidemia • Ischemic stroke

Characterising patients and lesions with plaque progression despite high-intensity LDL-C-lowering therapy: a multimodality serial intracoronary imaging study from the IBIS-4 and PACMAN-AMI trials (ESC 2026) - "All patients received high-intensity statin therapy; in PACMAN-AMI, patients were additionally randomised to alirocumab or placebo... One-quarter of AMI patients exhibit plaque progression in non-IRAs despite intensive LDL-C-lowering therapy. Prior statin use, higher on-treatment LDL-C, and absence of PCSK9 inhibitor therapy, but not factors unrelated to LDL-C, were associated with non-responder patients. Lipid-rich lesions were associated with an increased risk of plaque volume progression."

Clinical • Cardiovascular • Dyslipidemia • Hypertension • Myocardial Infarction • APOB • CRP

Risk-Weighted apoB Outperforms Unweighted apoB or Lipoprotein(a) as a Biomarker of Residual Cardiovascular Risk After Acute Coronary Syndrome and the Benefit of Alirocumab Therapy (AHA 2026) - "Abstract is embargoed at this time."

Biomarker • Acute Coronary Syndrome • Cardiovascular • APOB

Real-world outcomes of biweekly and monthly alirocumab regimens: a population-based analysis (ESC 2026) - "Among ACS patients, efficacy was comparable. Monthly dosing appears to be a convenient and effective option for maintaining lipid control without compromising safety."

Clinical • Real-world • Real-world evidence • Acute Coronary Syndrome • Cardiovascular • Dyslipidemia • Myocardial Infarction

Hypothyoidism, an underappreciated metabolic derangement causing dyslipidemia (ETA 2026) - "Rosuvastatin 20 mg daily was prescribed but two weeks later the patient developed severe myalgia and myositis the cardiologist stopped Rosuvastatin and alirocumab 75 mg/ml every two weeks...Levothyroxine was prescribed and increased gradually... Thyroid hormones play an important role in regulating the heart and lipid physiology. This case report underscores the importance of evaluation of secondary causes of dyslipidemia. Timely diagnosis and management of hypothyroidism can help avoid misdiagnosis and unnecessary treatment."

Acute Coronary Syndrome • Atherosclerosis • Cardiovascular • Constipation • Dyslipidemia • Endocrine Disorders • Familial Hypercholesterolemia • Gastroenterology • Gastrointestinal Disorder • Genetic Disorders • Immunology • Metabolic Disorders • Musculoskeletal Pain • Myositis • Pulmonary Disease

Lipoprotein(a), smoking, and diabetes are additive, but not interactive risk factors for major adverse cardiovascular events after acute coronary syndrome: An analysis of the ODYSSEY OUTCOMES trial (ESC 2026) - " ODYSSEY OUTCOMES compared the effects of alirocumab or placebo in patients with recent acute coronary syndrome on optimized statin therapy... Lp(a), smoking, and diabetes are additive but not interactive risk factors for MACE after ACS. Lp(a) remains an independent risk factor for MACE after adjustment for both smoking and diabetes."

Adverse events • Clinical • Acute Coronary Syndrome • Cardiovascular • Ischemic stroke • Myocardial Infarction

Effects of different statin-based lipid-lowering therapies on stabilization and regression of carotid plaque: a randomized open-label trial. (PubMed, Front Pharmacol) - P=N/A | "In this randomized open-label trial, participants were randomly assigned to one of four treatment groups: atorvastatin 20 mg/day (Statin), atorvastatin 10 mg/day + ezetimibe 10 mg/day (Statin_E), atorvastatin 10 mg/day + alirocumab 75 mg every 2 weeks (Statin_P), and atorvastatin 10 mg/day + ezetimibe 10 mg/day + alirocumab 75 mg every 2 weeks (Statin_EP). The trial was registered in the Chinese Clinical Trial Registry (No. ChiCTR2200058389) on 2022-04-08."

Journal • Atherosclerosis • Cardiovascular

A single arm phase II study of PCSK9 inhibitor, alirocumab, and PD-1 inhibitor, cemiplimab, in advanced immuno-refractory metastatic non-small cell lung cancer (TOP2201) (ELCC 2025) - P2 | "The secondary objectives are to evaluate the safety and tolerability of the combination, and to measure secondary efficacy endpoints including progression free survival (PFS), overall survival (OS), duration of responses (DOR) and disease control rates (DCR). The correlative objective is to evaluate the pharmacodynamic marker of change in LDL cholesterol levels measured in serial plasma collection while on treatment with alirocumab."

IO biomarker • Metastases • P2 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CD8