Repatha (evolocumab) / Dr. Reddy’s, Amgen, Astellas - LARVOL DELTA

Cholesterol ester storage disease (ENDO 2024) - "She was not aware of any treatment available and currently on atorvastatin 80 mg daily, evolocumab 140 mg every 14 days, and ezetimibe 10 mg daily.She follows up with hepatologist and cardiologist for annual imaging and monitoring the progression of her condition...Her last scan indicated fibrosis score of 4/ FIB-4 index 1.58, meaning intermediate risk of advanced fibrosis.Lab: AST 46, ALT 52, total cholesterol 137, LDL 59, HDL 57, TG 119Recent abdominal CT showed fatty liver disease with mild hepatomegaly.Physical exam: slightly enlarged liver noted.After reviewing all labs and imaging, I started her on sebelipase alfa 1mg/kg/dose IV every 14 days, and will follow up every 6 months...Abstracts presented at a news conference are embargoed until the date and time of the news conference. The Endocrine Society reserves the right to lift the embargo on specific abstracts that are selected for promotion prior to or during ENDO."

Cardiovascular • Diabetes • Fibrosis • Gastroenterology • Hepatology • Hypertension • Immunology • Liver Cirrhosis • Liver Failure • Metabolic Disorders • Portal Hypertension • Rare Diseases • Type 2 Diabetes Mellitus

Paradoxical Worsening of Dyslipidemia with Tirzepatide (ENDO 2024) - "However, this has yet to be shown with dual incretin receptor agonist therapies such as tirzepatide.Clinical Case: A 75-year-old female with dyslipidemia treated with evolocumab (LDL-C 183 mg/dLbefore treatment), type 2 diabetes mellitus, and class 1 obesity was switched from glimepiride to tirzepatide in an effort to address the above conditions...Out of concern for inefficacy of evolocumab, she was switched to inclisiran... To our knowledge, this is the first case report linking dual incretin receptor agonist therapy with worsening dyslipidemia.Reference: (1) Weinbrenner, T.; Züger, M; Jacoby, G.E; et al. Lipoprotein metabolism in patients with anorexia nervosa: a case-control study investigating the mechanisms leading to hypercholesterolaemia. British Journal of Nutrition."

Anorexia • Diabetes • Dyslipidemia • Genetic Disorders • Metabolic Disorders • Obesity • Type 2 Diabetes Mellitus

Association of lipid-lowering drug targets with risk of cutaneous melanoma: a mendelian randomization study. (PubMed, BMC Cancer) - "The study concludes that PCSK9 plays a significant role in the development of CM, and its inhibition is linked to a reduced risk of the disease."

Journal • Cutaneous Melanoma • Dyslipidemia • Melanoma • Metabolic Disorders • Oncology • Solid Tumor • PCSK9

Homozygous familial hypercholesterolemia surgical management and outcomes in up to 23 years follow up: a new Horizon for the Ross Procedure. (HEART FAILURE 2024) - "50% of patients were treated with plasmapheresis, all were on statins and 98% on ezetimibe. One patient was on Evolocumab and one on Lomitapide... The total number of patient who underwent aortic valve surgery was 24, 13 (54.2%) were male. The average age of the first surgical procedure was 18±6.9 years. The initial untreated LDL level average was 13.5±3.9 mmol/L."

Cardiovascular • Dyslipidemia

Management of dyslipidaemia with evolocumab in kidney transplant recipients (ERA-EDTA 2024) - "The criteria for its prescription were not achieving therapeutic c-LDL goals despite high-potency statins and ezetimibe treatment or adverse effects of statins (myalgias, hypertransaminasemia). In our experience, we observed good results with evolocumab, since total cholesterol and c-LDL reduced rapidly after starting the treatment. Furthermore, renal function maintained stable, no change in proteinuria and no other safety concerns were reported. In our case, neither tacrolimus nor everolimus trough levels remained unchanged and no immunological adverse outcomes were notified."

Clinical • Chronic Kidney Disease • Coronary Artery Disease • Dyslipidemia • Heart Failure • Musculoskeletal Pain • Nephrology • Pain • Transplant Rejection • Transplantation

EVOLVE-MI: EVOLocumab Very Early After Myocardial Infarction (clinicaltrials.gov) - P4 | N=6000 | Active, not recruiting | Sponsor: Amgen | Recruiting ➔ Active, not recruiting

Enrollment closed • Cardiovascular • Myocardial Infarction

EVACS II: Evolocumab in Patients With Acute MI (clinicaltrials.gov) - P2 | N=100 | Active, not recruiting | Sponsor: Johns Hopkins University | Trial completion date: Apr 2024 ➔ Oct 2024 | Trial primary completion date: Apr 2024 ➔ Oct 2024

Trial completion date • Trial primary completion date • Acute Coronary Syndrome • Cardiovascular • Myocardial Infarction

SIRIUS: In Silico Study Assessing the Impact of Inclisiran on Major Adverse Cardiovascular Events in Patients With Established Cardiovascular Disease (clinicaltrials.gov) - P=N/A | N=204691 | Completed | Sponsor: Novartis Pharmaceuticals | Active, not recruiting ➔ Completed | Trial completion date: Mar 2024 ➔ Dec 2023

Adverse events • Trial completion • Trial completion date • Atherosclerosis • Cardiovascular • Dyslipidemia

EVACS: Evolocumab in Acute Coronary Syndrome (clinicaltrials.gov) - P2 | N=60 | Active, not recruiting | Sponsor: Johns Hopkins University | Trial completion date: Apr 2024 ➔ Oct 2024 | Trial primary completion date: Apr 2024 ➔ Oct 2024

Trial completion date • Trial primary completion date • Acute Coronary Syndrome • Cardiovascular

Effect of alirocumab and evolocumab on all-cause mortality and major cardiovascular events : Systematic review and meta analysis (HEART FAILURE 2024) - "This abstract is Under Embergo untill 11 May - 09:45"

Retrospective data • Review • Cardiovascular

AMGEN REPORTS FIRST QUARTER 2024 FINANCIAL RESULTS (PRNewswire) - "Repatha sales increased 33% year-over-year to $517 million in the first quarter, driven by 44% volume growth, partially offset by 13% lower net selling price.....AMJEVITA/AMGEVITA (adalimumab) generated $168 million of sales in the first quarter. Sales increased 2% year-over-year primarily driven by international growth, partially offset by lower inventory levels and unfavorable change to estimated sales deductions....UPLIZNA (inebilizumab-cdon) generated $80 million of sales in the first quarter. UPLIZNA is used to treat adults with neuromyelitis optica spectrum disorders."

Sales • Cardiovascular • Crohn's disease • Dyslipidemia • Familial Hypercholesterolemia • Heterozygous Familial Hypercholesterolemia • Homozygous Familial Hypercholesterolemia • Immunology • Inflammatory Bowel Disease • Psoriasis • Rheumatoid Arthritis • Scleroderma • Systemic Sclerosis • Ulcerative Colitis

A new indication for bempedoic acid (Nexletol). (PubMed, Med Lett Drugs Ther) - No abstract available

Journal

Hypercholesterolemia: a literature review on management using tafolecimab: a novel member of PCSK9 monoclonal antibodies. (PubMed, Ann Med Surg (Lond)) - "Hyperlipidemia management includes various lipid-lowering drugs, including statins, Bempedoic acid, inclisiran, Lomitapide, ANGPTL3 inhibitors, and PCSK9 inhibitors...It has also been found that Tafolecimab has more affinity for PCSK9 and a longer duration of LDL-C reduction than other monoclonal antibody drugs such as evolocumab...Regulatory authorities like the FDA and EMA should also evaluate Tafolecimab's risks and benefits. In conclusion, Tafolecimab shows potential as an innovative therapeutic option for hypercholesterolaemia, particularly in patients with specific risk factors, but warrants additional research."

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

Young Investigator Winner- (200) Pericardial and Pleural Effusions After Evolocumab In a Patient with Severe Familial Hypercholesterolemia (NLA 2024) - No abstract available

Clinical • Pleural effusion • Dyslipidemia • Familial Hypercholesterolemia • Genetic Disorders • Metabolic Disorders • Respiratory Diseases

Current treatments for the management of homozygous familial hypercholesterolemia: a systematic review and commentary. (PubMed, Eur J Prev Cardiol) - "In practice, multiple treatments are required to treat HoFH. The sequencing of these should be made on an individualized basis, with consideration made to the benefits of each intervention."

Journal • Review • Dyslipidemia • Familial Hypercholesterolemia • Genetic Disorders • Homozygous Familial Hypercholesterolemia • Metabolic Disorders • Rare Diseases

EVOLVE-MI: EVOLocumab Very Early After Myocardial Infarction (clinicaltrials.gov) - P4 | N=6000 | Recruiting | Sponsor: Amgen | Trial completion date: Nov 2027 ➔ May 2027 | Trial primary completion date: Nov 2027 ➔ May 2027

Trial completion date • Trial primary completion date • Cardiovascular • Myocardial Infarction

BESAFE: Efficacy and Safety of Bempedoic Acid in Association With Anti-PCSK9 and Ezetimibe in Statin-intolerant Patients (clinicaltrials.gov) - P4 | N=130 | Not yet recruiting | Sponsor: University of Salerno

New P4 trial • Cardiovascular • Dyslipidemia • Metabolic Disorders

Important Notice for Patients: Discontinuation of Repatha (evolocumab) Pushtronex System (single-dose on-body infusor with prefilled cartridge) (Amgen Press Release) - "Amgen has made the decision to discontinue the Repatha Pushtronex System. If you are currently using the Repatha Pushtronex device, we kindly advise you to consult with your healthcare provider and transition to one of the other approved Repatha devices, preferably the SureClick Autoinjector. The decision to discontinue the Repatha Pushtronex device was made to uphold the high standards Amgen holds for patient experience, focusing on delivering optimal care for patients with cardiovascular disease and hyperlipidemia (high bad cholesterol). We plan to discontinue the Repatha Pushtronex on June 30th, 2024 and are committed to support patients as they transition."

Discontinued • Cardiovascular • Dyslipidemia • Familial Hypercholesterolemia • Heterozygous Familial Hypercholesterolemia • Homozygous Familial Hypercholesterolemia • Metabolic Disorders

ANTI-HMGCR ASSOCIATED IMMUNE MEDIATED NECROTIZING MYOPATHY: A RARE CASE AND TREATMENT INSIGHTS (ACC 2024) - "He had taken pravastatin for 20 years due to CAD...Alternatives include azathioprine, mycophenolate mofetil, tacrolimus, cyclosporine, or cyclophosphamide...Statins benefit many, but evolocumab, inclisiran, and bempedoic acid offer alternatives for contraindications. Due to its rarity, effective treatments for Anti-HMGCR Associated IMNM lack established clinical trial support. Initial management is to discontinue statin. Expert guidelines advise corticosteroids, methotrexate, rituximab, and/or IVIG."

Clinical • Cardiovascular • Coronary Artery Disease • Diabetes • Dyslipidemia • Hypertension • Metabolic Disorders • Myositis • Type 2 Diabetes Mellitus

Cholesterol-Lowering Strategies for Cardiovascular Disease Prevention: The Importance of Intensive Treatment and the Simplification of Medical Therapy. (PubMed, J Clin Med) - "Recent ESC/EAS guidelines advocate for a shift toward new risk estimation algorithms that better emphasize non-fatal cardiovascular events, lifetime risk prediction, and tailored pharmacological approaches, including statin + ezetimibe and triple therapy, in specific cases...Intracoronary imaging has revealed insights into the composition of plaque and demonstrated the significant regression that can be achieved through the use of statins such as rosuvastatin and atorvastatin. The positive effects of Proprotein Convertase Subtilisin/Kexin type 9 (PCSK9) inhibitors, particularly alirocumab and evolocumab, on plaque regression, have been demonstrated. Inclisiran, which targets PCSK9 gene expression, significantly reduces LDL cholesterol. The associated challenges include hesitancy to prescribe intensive regimens and limited treatment adherence, highlighting the need for pharmacological combinations to improve therapeutic outcomes."

Journal • Review • Atherosclerosis • Cardiovascular • Coronary Artery Disease • Dyslipidemia • PCSK9

The Use of Performance-Based Agreements in Common Diseases in EU3 and US (ISPOR 2024) - " A total of 24 PBAs (22 in the US, 2 in the UK, none in Germany or France) for 14 products (sitagliptin, sitagliptin/metformin, dulaglutide, exenatide, empagliflozin, dapagliflozin, liraglutide, sacubitril/valsartan, ticagrelor, alirocumab, evolocumab, inclisiran, lecanemab, budesonide/formoterol fumarate dihydrate) used in common diseases were identified. Although rare diseases and cancers remain the main focus of PBAs, the study results have shown that those mechanisms are also implemented in common diseases. While the prevalence of common diseases is increasing due to population aging, the use of PBAs in both Europe and the US is expected to grow to enable patients access to new therapies, optimize their budget impact, and decrease payer uncertainty."

Alzheimer's Disease • Cardiovascular • Chronic Obstructive Pulmonary Disease • CNS Disorders • Diabetes • Heart Failure • Immunology • Metabolic Disorders • Oncology • Pulmonary Disease • Rare Diseases • Respiratory Diseases • Type 2 Diabetes Mellitus

Safety of Monoclonal Antibodies Inhibiting PCSK9 in Pregnancy: Disproportionality Analysis in VigiBase®. (PubMed, Clin Pharmacol Ther) - "In conclusion, this study showed that, currently, there are no signals of increased reporting of spontaneous abortion with alirocumab and evolocumab compared with the full database and statins in VigiBase®. Notwithstanding, lack of disproportionality is not synonymous with safety and, as disproportionality analyses depend on the number of safety reports that progressively accumulate in VigiBase®, they should be repeated at regular intervals to confirm the results of the present study."

Journal

Effects of PCSK-9 Inhibitor Treatment Prior to Undergoing Primary Percutaneous Coronary Intervention in Patients With ST-segment Elevation Myocardial Infarction (clinicaltrials.gov) - P4 | N=84 | Recruiting | Sponsor: Beijing Luhe Hospital

New P4 trial • Cardiovascular • Myocardial Infarction

Effect of Empagliflozin with or without the Addition of Evolocumab on HDL Subspecies in Individuals with Type 2 Diabetes Mellitus: A Post Hoc Analysis of the EXCEED-BHS3 Trial. (PubMed, Int J Mol Sci) - "Over a 16-week period, empagliflozin with or without the addition of evolocumab led to a modest but significant increase in HDL-C. The rise in smaller-sized HDL particles was heterogeneous amongst the treatment combinations."

Journal • Retrospective data • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

The Role of PCSK9 Inhibition in the Care of Heart Transplant Recipients: A Single-Center Case Series (ISHLT 2024) - "The efficacy and utility of novel agents, such as PCSCK9 inhibitors (PCSK9i), in HT recipients require further investigation.Methods We identified adult HT recipients at our center on PCSK9i therapy with Evolocumab or Alirocumab. Patients treated with this novel lipid-lowering therapy achieved a persistently lower LDL than matched controls receiving statin therapy, many of whom had known CAV. HT recipients with more stringent LDL goals due to their CAV/CAD risk profile may benefit from PCSK9i therapy."

Clinical • Cardiovascular • Dyslipidemia • Transplantation