Evkeeza (evinacumab-dgnb) / Regeneron, Ultragenyx - LARVOL DELTA

Achieving the impossible: effective reduction of low-density lipoprotein cholesterol (LDL-C) in a patient with homozygous familial hypercholesterolemia. (PubMed, Endokrynol Pol) - "Not required for Clinical Vignette."

Journal • Atherosclerosis • Cardiovascular • Dyslipidemia • Familial Hypercholesterolemia • Genetic Disorders • Homozygous Familial Hypercholesterolemia • Metabolic Disorders

ANCHOR-POC: Study to Assess the Effects of Angiopoietin-like Protein 3 (ANGPTL3) Inhibition in Adult Participants With Diabetic Kidney Disease (clinicaltrials.gov) - P2 | N=270 | Not yet recruiting | Sponsor: Regeneron Pharmaceuticals

New P2 trial • Diabetic Nephropathy • Nephrology • Renal Disease • APOB

Therapeutic Plasma Exchange and Evinacumab for Homozygous Familial Hypercholesterolemia. (PubMed, JACC Case Rep) - "Persistence and use of combination therapies are required in treating HoFH, especially when patients experience intolerance to commonly used treatments. Premedications can prevent allergic and allergy-like reactions to therapies in HoFH."

Journal • Allergy • Atherosclerosis • Cardiovascular • Dyslipidemia • Familial Hypercholesterolemia • Genetic Disorders • Homozygous Familial Hypercholesterolemia • Immunology • Metabolic Disorders • ANGPTL3

Effects of evinacumab on high-density lipoprotein function in patients with homozygous familial hypercholesterolemia. (PubMed, J Clin Lipidol) - "HDL function assessed by serum CUC level increased by evinacumab in patients with genetically diagnosed HoFH, although the change of CUC was correlated with that of HDL cholesterol level."

Journal • Dyslipidemia • Familial Hypercholesterolemia • Genetic Disorders • Homozygous Familial Hypercholesterolemia • Metabolic Disorders

Inclisiran Nonresponse with PCSK9 Variant and Successful LDL-C Lowering with Evinacumab in a Patient with Homozygous Familial Hypercholesterolemia (AHA 2025) - "Despite adherence to maximum doses of LLT (Rosuvastatin, Ezetimibe, Bempedoic acid, Alirocumab) and aggressive lifestyle modifications (12lbs weight loss and a vegan diet), he did not reach target LDL <55mg/dL. Evinacumab works by facilitating clearance of lipoproteins via lipoprotein lipase and endothelial lipase and is independent of LDLR/PCSK9 pathway. This case highlights the importance of recognizing limitations in existing lipid-lowering strategies and the need for personalized treatment."

Clinical • Dyslipidemia • Familial Hypercholesterolemia • Genetic Disorders • Heterozygous Familial Hypercholesterolemia • Homozygous Familial Hypercholesterolemia • Metabolic Disorders • ANGPTL3 • APOB • LDLR • LPL

Breakthrough LDL-C reduction in a patient with autosomal recessive homozygous familial hypercholesterolemia: Efficacy of evinacumab after LDL-apheresis discontinuation. (PubMed, J Clin Lipidol) - "The introduction of evinacumab, an LDL receptor-independent lipid-lowering therapy, achieved robust and sustained LDL-C reduction, while eliminating the need for LDL-apheresis and reducing the indirect logistical burden of frequent hospital-based treatments in this patient with AR-HoFH."

Journal • Atherosclerosis • Cardiovascular • Coronary Artery Disease • Dyslipidemia • Familial Hypercholesterolemia • Genetic Disorders • Hematological Disorders • Homozygous Familial Hypercholesterolemia • Metabolic Disorders • Myocardial Infarction

PORTRAIT Survey: Patient-Centered Overview Related to Treatment Practices in Lipoprotein Apheresis: Italian Investigating Trajectories. (PubMed, Ther Apher Dial) - "The PORTRAIT survey would like to promote a network to better manage the patients on chronic LA."

Journal • Atherosclerosis • Cardiovascular • Dyslipidemia • Familial Hypercholesterolemia • Genetic Disorders • Homozygous Familial Hypercholesterolemia • Metabolic Disorders

Lessons from recent clinical trials for the prevention of acute pancreatitis in chylomicronemia syndromes. (PubMed, Curr Opin Endocrinol Diabetes Obes) - "These emerging mechanism-based therapies are reshaping the management of severe hypertriglyceridemia, offering targeted approaches to reduce triglycerides and acute pancreatitis risk. Ongoing studies will clarify long-term safety, durability of response, and optimal patient selection, providing a framework for improved clinical outcomes."

Journal • Dyslipidemia • Hepatology • Hypertriglyceridemia • Metabolic Disorders • Metabolic Dysfunction-Associated Steatotic Liver Disease • Pancreatitis • Severe Hypertriglyceridemia • ANGPTL3 • FGF21 • LPL

Future of angiopoietin-like protein 3 inhibitors as a therapeutic agent. (PubMed, Curr Opin Lipidol) - "ANGPTL3 inhibition offers an LDL receptor-independent means to lower atherogenic particles spanning from TRLs to LDL, complementing traditional lipid-lowering therapies. Evinacumab is practice-changing in HoFH, and RNA agents may soon broaden applicability to patients with mixed dyslipidemia and residual cardiovascular risk, pending cardiovascular outcomes trials."

Journal • Review • Atherosclerosis • Cardiovascular • Dyslipidemia • Familial Hypercholesterolemia • Genetic Disorders • Homozygous Familial Hypercholesterolemia • Metabolic Disorders • Mixed Hyperlipidemia • ANGPTL3

Evkeeza recorded sales of $16.7 million in the third quarter, up 57% as Ultragenyx continues to launch the drug in its territories outside of the United States. (TradingView)

Sales • Homozygous Familial Hypercholesterolemia

Antibody-Based Therapeutics for Hypercholesterolemia. (PubMed, Biologics) - "In recent years the mAbs, alirocumab and evolocumab, targeting proprotein convertase subtilisin/kexin type 9 (PCSK9) have become established worldwide as an additional treatment for patients not achieving LDL cholesterol goals on statins and ezetimibe, or sometimes as an alternative treatment in those with statin intolerance...New drug targets were identified to potentially reduce elevated triglyceride levels and the mAb angiopoietin-like 3 (ANGPTL3) inhibitor, evinacumab, was found to be effective in reducing LDL cholesterol in patients with homozygous familial hypercholesterolemia (FH) and has been approved for that indication. SHR-1918 is another mAb targeting ANGPTL3 being developed in China which may also be effective to treat homozygous FH...Another mAb at an early stage of development is MAR001 targeting angiopoietin-like 4 (ANGPTL4). The role for this remains to be established."

Journal • Review • Atherosclerosis • Cardiovascular • Dyslipidemia • Familial Hypercholesterolemia • Genetic Disorders • Homozygous Familial Hypercholesterolemia • Metabolic Disorders • ANGPTL3

ANGPTL3 Targeting Monoclonal Antibodies Lead to Robust Reductions in LDL-C, Triglycerides, ApoB, and Non-HDL-C in Dyslipidemic Patients: A Meta-Analysis of 5 Randomized Controlled Trials (AHA 2025) - "monoclonal antibodies targeting ANGPTL3 encompassing both evinacumab and the newer agent SHR-1918 consistently reduced LDL-C, triglycerides, and related lipid markers with a favourable tolerability profile. Further large, long-term studies are needed to fully establish their safety, clinical effectiveness, and potential to improve cardiovascular outcomes."

Retrospective data • Cardiovascular • Dyslipidemia • Metabolic Disorders • ANGPTL3 • APOB

IMPROVING MANAGEMENT OF HOMOZYGOUS FAMILIAL HYPERCHOLESTEROLAEMIA IN CHILDREN – COMBINING STANDARD INTERVENTIONS WITH LIPID APHERESIS AND EVINACUMAB (ESPN 2025) - "Dietary modification, statin and ezetimibe therapy failed to reduce LDLC to therapeutic levels- median 15.5mmol/l (range 9.7-25)...Evolocumab was trialled in 3 patients with no responders... Lipoprotein-apheresis is a well-tolerated, essential component of paediatric HoFH management. Achieving target LDLC remains challenging, even with lipoprotein-apheresis, however, target LDLC is now possible with the addition of evinacumab. References 1 Reijman MD et al, Atherosclerosis 2024; 392: 117525 2 Watts GF et al, Nat Rec Cardiol 2023; 20: 845"

Clinical • Atherosclerosis • Cardiovascular • Dyslipidemia • Familial Hypercholesterolemia • Homozygous Familial Hypercholesterolemia • Pediatrics • ANGPTL3

AN EXTRAORDINARY CASE OF HOMOZYGOUS FAMILIAL HYPERCHOLESTEROLEMIA AND TAKAYASU ARTERITIS MANAGED WITH LIPOPROTEIN-APHERESIS AND EVINACUMAB (ESPN 2025) - "Standard combination therapy (dietary modification, statin, and ezetimibe) achieved a 37% reduction in LDL-C (16.2 mmol/L)...This was managed with prednisolone, azathioprine, and adalimumab... This case highlights a highly effective approach to reducing LDL-C in a child at extreme risk for ASCVD utilizing lipoprotein apheresis in combination with the novel monoclonal antibody, evinacumab, in addition to standard combination therapy for managing HoFH. The 2023 ERKNET/ ESPN consensus statement1 acknowledges limitations to generating high-quality (Level A) evidence for lipoprotein apheresis in HoFH. Therefore, case reports and our experience continue to contribute valuable clinical insights to guide its use."

Clinical • Atherosclerosis • Cardiovascular • Dyslipidemia • Familial Hypercholesterolemia • Genetic Disorders • Homozygous Familial Hypercholesterolemia • Metabolic Disorders • Rare Diseases • Vasculitis • ANGPTL3

Breaking barriers: Innovative therapies for managing homozygous familial hypercholesterolemia. (PubMed, Exp Mol Pathol) - "Recent advancements have introduced novel pharmacological agents for treating HoFH (e.g. evolocumab, alirocumab, inclisiran and bempedoic acid), including cholesterol-lowering strategies that function independently of LDL-R such as lomitapide and evinacumab offering significant promise for managing this condition. However, disparities in the treatment of HoFH persist across different regions and countries. In this context, the review provides a comprehensive overview of established treatment modalities and emerging therapeutic agents for individuals with HoFH."

Journal • Review • Atherosclerosis • Cardiovascular • Dyslipidemia • Familial Hypercholesterolemia • Genetic Disorders • Homozygous Familial Hypercholesterolemia • Metabolic Disorders • Transplantation

Evinacumab Improved the Homozygous Familial Hypercholesterolemia Lipid Metabolism: A Case Report. (PubMed, J Atheroscler Thromb) - "In this case, evinacumab was highly efficacious against atherosclerosis-related markers and apolipoproteins, beyond simple LDL-C reduction, suggesting additional cardiovascular benefits. These findings provide mechanistic insights that may inform therapeutic strategies for the management of HoFH."

Journal • Atherosclerosis • Cardiovascular • Dyslipidemia • Familial Hypercholesterolemia • Genetic Disorders • Heterozygous Familial Hypercholesterolemia • Homozygous Familial Hypercholesterolemia • Metabolic Disorders • ANGPTL3 • APOA5 • APOB • APOE • CRP • IL6

Evkeeza (evinacumab-dgnb) ANGPTL3 Antibody Approved in the U.S. for Children as Young as 1 Year Old with Ultra-Rare Form of High Cholesterol (GlobeNewswire) - "The extended indication for Evkeeza was supported by clinical efficacy and safety data among 6 children living with HoFH (including pharmacokinetic data among 4 of these patients) who took part in either the U.S. expanded access program or ex-U.S. compassionate use program for Evkeeza."

FDA approval • Homozygous Familial Hypercholesterolemia

Discovery, Optimization, and Evaluation of Novel ANGPTL3 Modulators for the Treatment of Hyperlipidemia. (PubMed, J Med Chem) - "Evinacumab, a monoclonal antibody targeting ANGPTL3, was approved by the FDA for homozygous familial hypercholesterolemia in 2021...More importantly, compound 20 remarkably lowered serum levels of triglycerides (TG), total cholesterol, and LDL cholesterol (LDL-C) in high-fat-diet-induced hyperlipidemic models, with favorable pharmacokinetic properties and safety profiles. Collectively, a novel ANGPTL3 small-molecule modulator compound 20 with a distinct core structure was first reported, offering potential for therapeutic development in hyperlipidemia."

Journal • Dyslipidemia • Familial Hypercholesterolemia • Genetic Disorders • Homozygous Familial Hypercholesterolemia • Metabolic Disorders • ANGPTL3 • LPL

A Comprehensive Review of the Latest Approaches to Managing Hypercholesterolemia: A Comparative Analysis of Conventional and Novel Treatments: Part II. (PubMed, Pharmaceuticals (Basel)) - "It also examined non-pharmacological interventions and conventional therapies, with a detailed focus on statins and ezetimibe...It explores the mechanisms, clinical applications, safety profiles, and pharmacogenetic aspects of novel agents such as proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors (alirocumab, evolocumab), small interfering RNA (siRNA) therapy (inclisiran), adenosine triphosphate-citrate lyase (ACL) inhibitor (bempedoic acid), microsomal triglyceride transfer protein (MTP) inhibitor (lomitapide), and angiopoietin-like protein 3 (ANGPTL3) inhibitor (evinacumab). These agents offer targeted strategies for patients with high residual cardiovascular risk, familial hypercholesterolemia (FH), or statin intolerance. By integrating the latest advances in precision medicine, this review underscores the expanding therapeutic landscape in dyslipidemia management and the evolving potential for individualized care."

Journal • Review • Atherosclerosis • Cardiovascular • Dyslipidemia • Familial Hypercholesterolemia • Genetic Disorders • Metabolic Disorders • ANGPTL3

Multimodal Therapy Achieves Secondary Prevention LDL-C Targets in LDL-Receptor Null Homozygous Familial Hypercholesterolemia. (PubMed, JACC Case Rep) - "Effective treatment of homozygous familial hypercholesterolemia requires multimodal lipid-lowering therapies. With currently available treatments it is possible to achieve previously unattainable lowering of LDL-C to prevent vascular disease and the need for liver transplantation."

Journal • Cardiovascular • Coronary Artery Disease • Dyslipidemia • Familial Hypercholesterolemia • Genetic Disorders • Heart Failure • Homozygous Familial Hypercholesterolemia • Metabolic Disorders • Transplantation

Efficacy of evinacumab in patients with severe hypertriglyceridemia and a history of severe hypertriglyceridemia-related acute pancreatitis: A phase 2b trial. (PubMed, J Clin Lipidol) - P2 | "Although the sample size was too small to determine whether evinacumab can prevent AP, the data suggest evinacumab may be efficacious in lowering triglyceride concentrations in patients with sHTG and a history of sHTG-associated AP. Tolerability and safety of evinacumab was consistent with previous studies."

Journal • P2b data • Dyslipidemia • Hypertriglyceridemia • Pancreatitis • Severe Hypertriglyceridemia

Dyslipidemias as rare diseases. (PubMed, Cas Lek Cesk) - "Thanks to new hypolipidemic drugs such as evinacumab and lomitapide, patients today have a much better prognosis than in the past...Due to new causal metreleptine therapy, we can help patients with managing these metabolic complications significantly...Therapy with volanesorsen leads to a reduction of hypertriglyceridemia, thereby reducing the risk of developing acute pancreatitis. Although these diseases are rare, it is necessary to think about them and diagnose them early. Interdisciplinary cooperation is essential during search and treatment of these patients."

Journal • Atherosclerosis • Cardiovascular • Dyslipidemia • Familial Hypercholesterolemia • Homozygous Familial Hypercholesterolemia • Hypertriglyceridemia • Lipodystrophy • Metabolic Disorders • Pancreatitis • Rare Diseases

Outpatient monthly plasmapheresis with post-PLEX evinacumab in pediatric homozygous familial hypercholesterolemia: a case report on port access and immunoglobulin preservation. (PubMed, Front Pediatr) - "This case, to our knowledge, describes the first pediatric outpatient implementation of monthly plasmapheresis with post-PLEX Evinacumab infusions, enabled by dual-port access and Octaplasma support to maintain immunoglobulin levels. This report highlights procedural innovations that enabled sustained therapy and emphasizes the need for standardized approaches for combining Evinacumab with extracorporeal treatment in pediatric HoFH."

Journal • Cardiovascular • Dyslipidemia • Familial Hypercholesterolemia • Genetic Disorders • Homozygous Familial Hypercholesterolemia • Metabolic Disorders • Pediatrics • ANGPTL3

Evinacumab as an Effective Treatment Option for Refractory Hypertriglyceridemia (ENDO 2025) - "Despite using atorvastatin 80 mg daily, fenofibrate 162 mg daily, icosapent ethyl 2 g twice daily, and evolocumab 140 mg every 2 weeks, she continued to have hypertriglyceridemia. Evinacumab may be an effective alternative agent for the management of chronic hypertriglyceridemia based on the robust effects seen in our patient. Future research is needed to explore evinacumab's therapeutic targets beyond LDL-C to better modify risk factors for atherosclerosis, as well as CAV progression in heart transplant recipients."

Atherosclerosis • Cardiomyopathy • Cardiovascular • Diabetes • Dyslipidemia • Familial Hypercholesterolemia • Genetic Disorders • Homozygous Familial Hypercholesterolemia • Hypertriglyceridemia • Metabolic Disorders • Pancreatitis • Severe Hypertriglyceridemia • Type 2 Diabetes Mellitus • ANGPTL3 • APOB

Health Canada Extends the Approval of Evkeeza (evinacumab) to Children as Young as 6-months Old with Homozygous Familial Hypercholesterolemia (HoFH) (GlobeNewswire) - "Ultragenyx Pharmaceutical Inc...announced that Health Canada has extended the approval of Evkeeza (evinacumab) as an adjunct to diet and other low-density lipoprotein cholesterol (LDL-C) lowering therapies to treat children aged 6-months and older with homozygous familial hypercholesterolemia...The pharmacokinetics and efficacy of the drug in pediatric patients aged 6 months to less than 5 years with HoFH have been predicted from a model-based extrapolation analysis...Based on the currently available data, the safety profile in pediatric patients aged 6-months to 5 years old is expected to be similar to the safety profile in older pediatric patients. No new safety concerns have been identified in the compassionate use program...Evkeeza is reimbursed and commercially available to prescribe for appropriate patients with HoFH in Canada via private drug plans and through the public drug program in Quebec, the UK, U.S., Italy, Japan, the Netherlands, Spain and Luxembourg."

Canada approval • Reimbursement • Homozygous Familial Hypercholesterolemia