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

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

AIFA Board of Directors approves the reimbursability... [Google translation] (Italian Medicines Agency) - "The new medicine that will be eligible for reimbursement is Velsipity (etrasimod), indicated for the treatment of patients aged 16 years or older with moderate to severe ulcerative colitis (UC) with inadequate response, habituation or intolerance to conventional therapy or a biological agent...The therapeutic indication extensions concern the multiple sclerosis (MS) medicine Aubagio (teriflunomide), the antithrombotic Ceprotin (protein C), the monoclonal antibody Evkeeza (evinacumab) for homozygous familial hypercholesterolaemia (two indication extensions)..."

Reimbursement • Genetic Disorders • Homozygous Familial Hypercholesterolemia • Multiple Sclerosis • Ulcerative Colitis

Correction to: Evinacumab for Pediatric Patients With Homozygous Familial Hypercholesterolemia. (PubMed, Circulation) - No abstract available

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

Long-term safety and effectiveness of evinacumab in people 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

Long-term experience with lomitapide treatment in patients with homozygous familial hypercholesterolemia: Over 10 years of efficacy and safety data. (PubMed, J Clin Lipidol) - "Over the last decade, numerous clinical trials, real-world evidence studies, and case studies/series have investigated the LDL-C-lowering efficacy/effectiveness and safety of lomitapide. Lomitapide is an effective treatment option for lowering LDL-C in patients with HoFH who are refractory to LDLR-dependent therapies, such as statins, ezetimibe, and PCSK9i."

Journal • Review • Atherosclerosis • Cardiovascular • Dyslipidemia • Familial Hypercholesterolemia • Genetic Disorders • Homozygous Familial Hypercholesterolemia • Metabolic Disorders • Pediatrics • Rare Diseases • APOB

Global disparities in access to lipid-lowering therapies for patients with homozygous familial hypercholesterolemia - A physician survey. (PubMed, J Clin Lipidol) - P | "Our results confirm significant global disparities in LLT registration, reimbursement, and access between high-income and nonhigh-income countries. Improving LLT availability and accessibility, particularly in nonhigh-income countries, is essential to improve outcomes in patients with HoFH."

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

Beyond homozygous familial hypercholesterolemia – emerging therapy for severe familial hypercholesterolemia phenotypes (NLA 2025) - "Methods Case 1: A patient with LDL-C > 400 mg/dL and APOB/PCSK9 VUS showed inadequate response to rosuvastatin, ezetimibe and evolocumab but achieved significant LDL-C reduction after starting evinacumab. As seen in our four cases, double heterozygotes and HoFH phenocopies may present with HoFH-like features and with resistance to standard lipid-lowering therapy. As Rosenson suggests, LDLR receptor independent therapies like evinacumab, may offer hope for improved LDL-C reduction and prevention of atherosclerotic cardiovascular events in refractory hyperlipidemia regardless of genetic profile."

Atherosclerosis • Cardiovascular • Dyslipidemia • Familial Hypercholesterolemia • Genetic Disorders • Heterozygous Familial Hypercholesterolemia • Homozygous Familial Hypercholesterolemia • Metabolic Disorders • APOB • APOE • LDLR • PCSK9

Exploring EVKEEZA (evinacumab-dgnb) (NLA 2025) - "Sponsored by Regeneron Pharmaceuticals; Lunch provided by the NLA Early detection and intervention in HoFH* Mechanism of action for EVKEEZA* Clinical efficacy and safety of EVKEEZA*myRARE: Patient support for EVKEEZA* 48 week study (24 week double-bline treatment period followed by 24-week open-lable treatment period)."

Dyslipidemia • Homozygous Familial Hypercholesterolemia

ANGPTL3: A Breakthrough Target in Treatment for Dyslipidemia and Atherosclerosis. (PubMed, J Atheroscler Thromb) - "Despite conventional treatment with statins, ezetimibe, or PCSK9 inhibitors, there are cases of familial hypercholesterolemia (FH) in which LDL-C levels cannot be sufficiently lowered to the target level, resulting in failure to prevent CVD...In fact, evinacumab, an anti-ANGPTL3 monoclonal antibody, has been shown to substantially reduce LDL-C and TG levels, even in FH patients with LDL receptor gene mutations who are resistant to the conventional treatments described above. Clinical trials have also shown that siRNA therapeutics, such as zodasiran and solbinsiran, improve lipid profiles in patients with dyslipidemia. Recently, we have begun developing a peptide-based anti-ANGPTL3 vaccine and confirmed in a preclinical FH mouse model that it significantly decreases LDL-C and TG levels, reduces atherosclerotic lesions and maintains long-term efficacy without adverse effects. In this review, we discuss the promising advances in ANGPTL3-targeted therapeutics that may..."

Journal • Atherosclerosis • Cardiovascular • Dyslipidemia • Familial Hypercholesterolemia • Genetic Disorders • Hypertriglyceridemia • Metabolic Disorders • ANGPTL3 • LPL

Real-World Effectiveness and Safety of Evinacumab in Children and Adults With Homozygous Familial Hypercholesterolemia: A Multisite US Perspective. (PubMed, Arterioscler Thromb Vasc Biol) - "Fifty percent were female, 66.7% had ASCVD, 87.5% were on a statin, 83.3% were on ezetimibe, 66.7% were on PCSK9i, 24% were on lomitapide, and 33.3% were undergoing lipoprotein apheresis. Treatment was discontinued by 1 patient because of back pain. Across 6 US academic medical centers, evinacumab was generally well tolerated by patients with HoFH and lowered LDL-C by ≈50%, consistent with results from clinical trials."

Journal • Real-world evidence • Back Pain • Dyslipidemia • Familial Hypercholesterolemia • Genetic Disorders • Homozygous Familial Hypercholesterolemia • Metabolic Disorders • Musculoskeletal Pain • Pain • ANGPTL3

Evinacumab and reduced lipoprotein apheresis in pediatric homozygous familial hypercholesterolemia: a retrospective study on LDL-C. (PubMed, Atherosclerosis) - "Evinacumab effectively lowers LDL-C in children and adolescents with HoFH. However, its ability to facilitate long-term reduction in LA frequency was not shown and remains unclear."

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

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