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

Safety and effectiveness of evinacumab in an infant with homozygous familial hypercholesterolemia: A new renaissance for the very young? (PubMed, J Clin Lipidol) - "The treatment with evinacumab was safe and effective; LDL cholesterol, triglycerides, and apolipoprotein B concentrations all decreased by over 80%. Our findings suggest that evinacumab is a safe and effective option for treating very young patients with HoFH who do not respond to conventional therapies."

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

4024 - Exploring EVKEEZA® (evinacumab-dgnb) (ACC 2025) - "• Early detection and intervention in HoFH• Mechanism of action for EVKEEZA• Clinical efficacy and safety of EVKEEZA• Long-term (48 weeks*) efficacy and safety of EVKEEZA• Dosing and administration for EVKEEZA• myRARE®: Patient support for EVKEEZA*48-week study (24-week double-blind treatment period followed by 24-week open-label treatment period).Industry-Expert Theater presentations are not part of ACC.25, as planned by its Program Committee, and do not qualify for continuing medical education (CME), continuing nursing education (CNE) or continuing education (CE) credit. Sponsored by Regeneron"

Dyslipidemia • Homozygous Familial Hypercholesterolemia

Exploring EVKEEZA® (evinacumab-dgnb) - Matthew J. Budoff (ACC 2025) - "Sponsored by Regeneron"

PROLONGED SURVIVAL IN HOMOZYGOUS FAMILIAL HYPERCHOLESTEROLEMIA - Andrew Cesmat (ACC 2025) - "She declined LDL apheresis and attempted medical management with high-intensity statins, ezetimibe, PCSK9 inhibitors, and bempedoic acid, but required four-vessel coronary artery bypass. Homozygous forms of hypercholesterolemia are rarely seen in adulthood as survival was previously uncommon due to lack of timely diagnosis and limited treatment options. The cases presented highlight the evolving management of patients with genetic dyslipidemias emphasizing the importance of early diagnosis, aggressive treatment strategies, and the need for continued advancements in care."

Dyslipidemia • Familial Hypercholesterolemia • Genetic Disorders • Gout • Homozygous Familial Hypercholesterolemia • Inflammatory Arthritis • Metabolic Disorders • Rheumatology • ANGPTL3

Evinacumab for Homozygous Familial Hypercholesterolemia: The Italian Cohort of the ELIPSE HoFH Study. (PubMed, Adv Ther) - P3 | "Evinacumab substantially lowered LDL cholesterol levels in patients with HoFH regardless of the degree of LDL receptor function, with low levels sustained over 5 years of follow-up."

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

Safety and Effectiveness of Evinacumab for the Treatment of Homozygous Familial Hypercholesterolemia (clinicaltrials.gov) - P3 | N=10 | Completed | Sponsor: Daniel Gaudet | Active, not recruiting ➔ Completed

Trial completion • Dyslipidemia • Familial Hypercholesterolemia • Genetic Disorders • Homozygous Familial Hypercholesterolemia • Metabolic Disorders

A Case with Oligogenic Familial Hypercholesterolemia Treated by Combination Therapy of Statin, Ezetimibe, PCSK9 Inhibitor, and Lomitapide. (PubMed, Intern Med) - "His LDL-cholesterol level was well controlled by the introduction of a proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor and lomitapide (approximately 30 mg/dL). Combination therapy is effective in reducing LDL levels."

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

Comparison of Model-Predicted and Observed Evinacumab Pharmacokinetics and Efficacy in Children Aged < 5 Years With Homozygous Familial Hypercholesterolemia. (PubMed, CPT Pharmacometrics Syst Pharmacol) - "Based on the actual patient dosing and plasmapheresis history, model-predicted evinacumab and LDL-C concentrations were comparable to the observed data collected in the managed access program. Overall, this analysis provides evidence for the use of evinacumab 15 mg/kg iv q4w dosing regimen in 6-month-old to 5-year-old patients."

Journal • PK/PD data • Dyslipidemia • Familial Hypercholesterolemia • Genetic Disorders • Homozygous Familial Hypercholesterolemia • Metabolic Disorders • Pediatrics • ANGPTL3

Population Pharmacokinetics and Exposure-Response Modeling for Evinacumab in Children, Adolescents, and Adults With Homozygous Familial Hypercholesterolemia. (PubMed, CPT Pharmacometrics Syst Pharmacol) - "Model-based simulations showed that while evinacumab exposure is reduced with decreasing age/body weight, younger patients are predicted to have a comparable or greater magnitude of LDL-C reduction than older patients at a dose of 15 mg/kg. Overall, the model adequately predicted the evinacumab exposure and LDL-C reduction in children, adolescents, and adults with HoFH, aligning with clinically relevant observations."

Journal • PK/PD data • Dyslipidemia • Familial Hypercholesterolemia • Genetic Disorders • Homozygous Familial Hypercholesterolemia • Metabolic Disorders • Pediatrics • ANGPTL3

Evinacumab for the treatment of homozygous familial hypercholesterolaemia: first patient case report in Switzerland. (PubMed, Swiss Med Wkly) - "As a result of this newly introduced treatment, the patient's LDL cholesterol levels were reduced by more than half, achieving recommended target values of secondary prevention for the first time. This case underscores the efficacy of evinacumab in achieving LDL cholesterol targets in homozygous familial hypercholesterolaemia patients and highlights the importance of early identification and treatment initiation."

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

Effects of Inclisiran, Alirocumab, Evolocumab, and Evinacumab on Lipids: A Network Meta-Analysis. (PubMed, Rev Cardiovasc Med) - "Evinacumab shows the best safety profile with the lowest incidence of AEs. CRD42024570445, https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=570445."

Journal • Retrospective data • Review • Dyslipidemia

Ultragenyx announces COFEPRIS approval of Evkeeza (evinacumab) for the treatment of Homozygous Familial Hypercholesterolemia (HoFH). [Google translation] (GlobeNewswire) - "Ultragenyx México S. de RL de CV...announces the regulatory approval of Evkeeza (evinacumab) in Mexico. Evkeeza has been approved by the Federal Commission for the Protection against Sanitary Risks (COFEPRIS) for the treatment of adults and pediatric patients 5 years of age and older diagnosed with homozygous familial hypercholesterolemia (HoFH)."

Approval • Homozygous Familial Hypercholesterolemia

Treatment With Evinacumab Links a New Pathogenic Variant in the LPL Gene to Persistent Chylomicronemia. (PubMed, J Endocr Soc) - "The efficacy of ANGPTL3 inhibitors in decreasing TG levels is LPL-dependent. Poor response to evinacumab supports the evidence that the E282X variant in the LPL gene is pathogenic and associated with persistent chylomicronemia (FCS phenotype)."

Journal • Dyslipidemia • Familial Chylomicronemia Syndrome • Hypertriglyceridemia • Pancreatitis • Severe Hypertriglyceridemia • ANGPTL3 • LPL

High burden of disease in patients with homozygous familial hypercholesterolemia despite recent advances in therapies and updated guidelines: A real-world study. (PubMed, J Clin Lipidol) - "This real-world study showed that patients with HoFH are undertreated, resulting in suboptimal control of LDL-C levels and a high prevalence of ASCVD."

HEOR • Journal • Real-world evidence • Atherosclerosis • Cardiovascular • Coronary Artery Disease • Dyslipidemia • Familial Hypercholesterolemia • Genetic Disorders • Heart Failure • Homozygous Familial Hypercholesterolemia • Metabolic Disorders • Rare Diseases

Evinacumab as an adjunct to lipid apheresis in an infant with homozygous familial hypercholesterolemia. (PubMed, J Pediatr Endocrinol Metab) - "The administration of evinacumab can significantly lower the concentration of LDL cholesterol in infants and thus reduce the frequency of lipid apheresis."

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

Evinacumab for children with homozygous familial hypercholesterolemia: a plain language summary. (PubMed, Future Cardiol) - No abstract available

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

Efficacy of a novel PCSK9 inhibitory peptide alone and with evinacumab in a mouse model of atherosclerosis. (PubMed, J Lipid Res) - "Additionally, evaluation of lipid concentrations in cynomolgus monkeys revealed the beneficial effects of the PCSK9 inhibitory peptide on total cholesterol and LDL-C levels. Together these data demonstrate that treatment with evinacumab and PCSK9 inhibitory peptide alone and in combination reduces lipids, development of atherosclerosis and improves lesion composition, making it a promising approach for treatment of atherosclerosis."

Journal • Preclinical • Atherosclerosis • Cardiovascular • ANGPTL3 • APOE

Molecular Therapeutics in Development to Treat Hyperlipoproteinemia. (PubMed, Mol Diagn Ther) - "Inhibition of APOC3 messenger RNA expression by olezarsen and plozasiran significantly lowers plasma triglyceride levels and markedly reduces pancreatitis risk in patients with familial chylomicronemia syndrome. Finally, angiopoietin-like protein 3 inhibition by the monoclonal antibody evinacumab has transformed management of patients with homozygous familial hypercholesterolemia. Together, these novel agents expand the therapeutic cache, offering personalized lipid-lowering strategies for high-risk patients with hyperlipoproteinemia, improving clinical outcomes and addressing previously unmet medical needs."

Journal • Review • Atherosclerosis • Cardiovascular • Dyslipidemia • Familial Chylomicronemia Syndrome • Familial Hypercholesterolemia • Genetic Disorders • Homozygous Familial Hypercholesterolemia • Metabolic Disorders • Pancreatitis

Genetically mimicked effects of evinacumab on psoriasis: a drug target Mendelian randomization study. (PubMed, Asia Pac J Clin Nutr) - "The genetically mimicked effect of evinacumab has the potential to reduce the risk of psoriasis and arthropathic psoriasis by lowering circulating triglyceride and LDL-C concentrations, respectively. These findings suggest that evinacumab may help prevent psoriasis and psoriatic arthritis progression in clinical practice."

Journal • Dermatology • Dyslipidemia • Immunology • Inflammatory Arthritis • Metabolic Disorders • Psoriasis • Psoriatic Arthritis • Rheumatology • Seronegative Spondyloarthropathies • ANGPTL3

Exploring emerging pharmacotherapies for type 2 diabetes patients with hypertriglyceridemia. (PubMed, Expert Opin Pharmacother) - "These were identified by a PubMed search and mainly focus on pemafibrate and the drugs targeting apolipoprotein C3 (apoC3) and angiopoietin-like 3 (ANGPTL3)...Inhibitors of apoC3 are effective in reducing triglycerides even in familial chylomicronaemia syndrome and olezarsen and plozasiran in this group are being studied in patients with combined hyperlipidemia. The ANGPTL3 inhibitor evinacumab has been approved for homozygous familial hypercholesterolemia and other ANGPTL3 inhibitors may prove be useful to reduce triglycerides in T2D."

Journal • Review • Cardiovascular • Diabetes • Dyslipidemia • Familial Chylomicronemia Syndrome • Familial Hypercholesterolemia • Genetic Disorders • Homozygous Familial Hypercholesterolemia • Hypertriglyceridemia • Metabolic Disorders • Type 2 Diabetes Mellitus • ANGPTL3

European Commission (EC) Extends the Approval of Evkeeza (evinacumab) to Children as Young as 6-months Old with Homozygous Familial Hypercholesterolemia (HoFH) (GlobeNewswire) - "Ultragenyx Pharmaceutical Inc...today announced that the European Commission (EC) has extended the approval of Evkeeza (evinacumab) as an adjunct to diet and other lipid-lowering therapies to treat children aged 6-months and older with homozygous familial hypercholesterolemia (HoFH). Evkeeza, an angiopoietin-like 3 (ANGPTL3) inhibitor, is the first medicine indicated for children in the European Union (EU) as young as 6-months old to treat HoFH, a disease associated with dangerously high levels of low-density lipoprotein cholesterol (LDL-C)....This EC decision follows the positive recommendation received from the Committee for Medicinal Products for Human Use in November 2024.The efficacy of Evkeeza in paediatric patients aged 6 months to less than 5 years with HoFH has been predicted from a model-based extrapolation analysis."

EMA approval • Familial Hypercholesterolemia • Homozygous Familial Hypercholesterolemia

NHS England Rolls Out Evkeeza (evinacumab) for Eligible Adults and Adolescents Aged 12 Years and Older with Homozygous Familial Hypercholesterolaemia (HoFH) (GlobeNewswire) - "Ultragenyx Pharmaceutical....today announced that NHS England has implemented the commissioning of Evkeeza (evinacumab) following the National Institute for Health and Care Excellence (NICE) final guidance in September. The use of Evkeeza in eligible people aged 12 years and older will be routinely commissioned by NHS England in line with the NICE TA and will be available in seven hospital trusts in England. In addition, prior approval forms are in place to enable access for children aged 5 to 11 years, via the NHS England Commissioning Medicines for Children policy."

NICE • Familial Hypercholesterolemia

4-Phenylbutyric Acid Reduces Endoplasmic Reticulum Retention and Partially Restores Function of LDLR p.D622N Mutation In Vitro: A Potential Therapy for Hypercholesterolemia (AHA 2024) - "Treatment with statins, ezetimibe, PCSK9 monoclonal antibodies (Alirocumab and Evolocumab), and inclisiran, which target LDLR function, resulted in minimal LDL reduction.In China, evinacumab is not available, so the patient has to rely on long-term lipid apheresis (plasma exchange). Genetic testing revealed the proband harbored three mutations in the LDLR gene: c.1864G>A (p.D622N), c.1448G>A (p.W483*), and c.292G>A (p.G98S). 4-phenylbutyric acid may serve as a potential therapeutic approach for FH patients with LDLR mutations causing ER retention."

Preclinical • Dyslipidemia • Familial Hypercholesterolemia • Genetic Disorders • Metabolic Disorders • LDLR

A drug target Mendelian randomization study of triglyceride lowering therapies for aortic stenosis (AHA 2024) - "Next, we identified genetic proxies for the TG-lowering therapies fenofibrate, volanesorsen and evinacumab as single nucleotide polymorphisms (SNPs) within 200kb of the target genes (PPARA, APOC3 and ANGPTL3, respectively) which were also significantly associated with TG at p<5x10-8 and clumped using threshold r2<0.1. Genetically proxied APOC3 inhibition, but not PPARA or ANGPTL3, was robustly associated with reduced risk of AS. This suggests that APOC3 inhibition may be a therapeutic opportunity for AS management and warrants further research in the clinical trial setting."

Hypertriglyceridemia • ANGPTL3 • PPARA

Challenges in The Treatment of Complex Cases of Homozygous Familial Hypercholesterolemia (ESPE 2024) - "Dietary recommendations, physical activity and statin therapy were suggested, gradually adding Ezetimibe and Evolocumab. FH is often underdiagnosed and undertreated, particularly in children, since physical signs are rarely observed. Lipid profile screening would guarantee early identification of these patients, and genetic analysis should be performed when family history or clinical data are very suggestive. Treatment options in the pediatric population are limited but the efficacy of newly emerging drugs, like Evinacumab, with tolerability and minimal invasiveness, represents an excellent opportunity for increasing patients'life expectancy and improving their quality of life."

Clinical • Atherosclerosis • Cardiovascular • Coronary Artery Disease • Dermatology • Dyslipidemia • Familial Hypercholesterolemia • Genetic Disorders • Homozygous Familial Hypercholesterolemia • Metabolic Disorders • Pediatrics