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

YN001-004 in Patients With Coronary Atherosclerosis in Australia (clinicaltrials.gov) - P2 | N=12 | Not yet recruiting | Sponsor: Beijing Inno Medicine Co., Ltd.

New P2 trial • Acute Coronary Syndrome • Atherosclerosis • Cardiovascular • Coronary Artery Disease • Dyslipidemia

Association Between Small Interfering RNA Therapy and Autoimmune Diseases: U.S. Prospective Cohort Study (ACR Convergence 2024) - "In our study, inclisiran users demonstrated a significantly higher risk of IBD compared to alirocumab/evolocumab users. Future research should investigate the underlying mechanisms driving this increased risk and evaluate long-term safety across diverse populations. Clinically, monitoring for IBD symptoms in patients receiving inclisiran is recommended to ensure timely intervention and management."

Clinical • Dyslipidemia • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammation • Inflammatory Bowel Disease

PCSK-9-inhibitor therapy improves endothelial function in high-risk patients with cardiovascular disease. (PubMed, Clin Res Cardiol) - "Our data indicate that endothelial function improved with evolocumab treatment in high-risk patients on statin therapy with preexisting cardiovascular disease. Our results contribute to the mechanistic explanation why lower incidence of the cardiovascular composite endpoint has been demonstrated in the FOURIER study."

Journal • Cardiovascular

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

Proprotein Convertase Subtilisin/Kexin Type 9 Inhibitors and Lipid Reduction: A Network Meta-Analysis (AHA 2024) - "In patients with hypercholesterolemia and/or hyperlipidemia treated with medium-intensity statins, tafolecimab and evolocumab (either Q2W or Q4W) might be preferred choices for lowering LDL-C. Additionally, tafolecimab (either Q2W or Q4W) appears to be the most effective agent for reducing lipoprotein(a) levels."

Retrospective data • Dyslipidemia • Metabolic Disorders

Inclisiran in Routine Clinical Practice: Results from a Nationwide Study of >5,000 Patients (AHA 2024) - "In a large cohort of patients administered Inclisiran in routine clinical practice, Inclisiran use was associated with substantial decreases in LDL levels, but those decreases were nonetheless smaller than the effects seen in randomized controlled trials of the drug."

Clinical • Dyslipidemia • Metabolic Disorders

PCSK9 Inhibitors for ASCVD Risk Reduction in Asian Populations — a meta-analysis of efficacy and safety profiles (AHA 2024) - "Inclisiran was used in 3 studies, evolocumab in 5, alirocumab in 2, and tafolecimab in 1, alongside statins or ezetimibe.PCSK9i reduced LDL by -74.21 mg/dL and increased the likelihood of >50% LDL reduction compared to placebo (RR: 37.41, 95% CI: 16.31-85.82, P < 0.00001; I^2: 0%). The considerable heterogeneity in LDL reduction may result from variations in dosing, different agents used, baseline LDL levels, and geographical diversity. Future research should explore effects across more ethnicities to enhance generalizability."

Retrospective data • Dyslipidemia • Metabolic Disorders

Non-statin Medication Utilization under Medicare Part D Population (AHA 2024) - "The non-statin medications included in these studies are bempedoic acid, evolocumab, alirocumab, inclisiran, and evanicumab. How the Inflation Reduction Act of 2022 will affect drug utilization is yet to be seen.LimitationThe pattern of data used may not be generalizable to other payer demographics. Policy changes can affect the comparability of data over different periods.ConclusionFrom 2020 to 2022, the number of claims, beneficiaries, and total spending on various lipid-lowering agents steadily increased."

Clinical • Medicare • Reimbursement • US reimbursement

Access to Lipid-Lowering Therapies is Limited by Payer Coverage Restrictions and High Out-of-Pocket Costs on Medicare Prescription Drug Plans (AHA 2024) - "Medications studied included generic atorvastatin, rosuvastatin, and ezetimibe as well as brand-name PCSK9i, bempedoic acid, and icosapent ethyl.Results/Data: Among 4,754 plans, coverage of lipid-lowering therapies varied widely. Generic atorvastatin, rosuvastatin, and ezetimibe were universally covered, while branded therapies such as alirocumab and bempedoic acid were covered by only one-half and one-third of plans, respectively. Nearly all plans providing coverage placed non-generic medications in high cost-sharing tiers and required prior authorization for alirocumab (96% of plans), evolocumab (94% of plans), and bempedoic acid (93% of plans). Lack of coverage, widespread prior authorization requirements, and high out-of-pocket costs jeopardize access to non-generic lipid-lowering medications, and likely contribute to their low utilization in the mitigation of cardiovascular disease risk. Some cost toxicity for patients may be alleviated by the Inflation Reduction..."

Medicare • Reimbursement • US reimbursement • Dyslipidemia

Changes in high-sensitivity cardiac troponin I and associated cardiovascular risk: Analyses From the FOURIER Trial (AHA 2024) - "Data are scarce regarding changes of hs-cTnI in a stable setting.Aims: To study baseline and changes of hs-cTnI in pts with atherosclerotic CV disease (ASCVD), and the association with risk of major CV events. We measured hs-cTnI (Abbott ARCHITECT) at baseline (BL) and 24 weeks (wks) in 20,718 pts enrolled in a nested biomarker study of the FOURIER trial, which tested the PCSK9i evolocumab vs. placebo in pts with ASCVD on statin and LDL >70 or non-HDL >100 mg/dL... Changes in hs-cTnI are associated with the risk of future CV events. Serial measurements of hs-cTnI may aid in reclassification of CV risk and the identification of pts whose CV risk changes with time."

Atherosclerosis • Cardiovascular • Dyslipidemia • TNNI3

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

Clinical characteristics and treatment of high-risk cardiovascular patients without prior myocardial infarction or stroke: VESALIUS-REAL - results from US (AHA 2024) - P3 | "The effect of evolocumab in this population is being investigated in an ongoing clinical trial (NCT03872401: Effect of Evolocumab in Patients at High Cardiovascular Risk Without Prior Myocardial Infarction or Stroke [VESALIUS-CV])... In a large cohort of VESALIUS-CV like US patients, the majority had LDL-C sub-optimally managed with most not taking any LLT. This finding suggests an opportunity to reduce the treatment gap and improve lipid management in this population."

Clinical • Cardiovascular • Coronary Artery Disease • Diabetes • Dyslipidemia • Metabolic Disorders • Myocardial Infarction • APOB

Statin and PCSK9 Inhibitor Utilization and Spending in Medicaid between 2018 to 2022: A National Analysis (AHA 2024) - "Repatha Sureclick was the most filled PCSK9i in Medicaid with 80,503 fills in 2022, representing $43.9 million in total Medicaid spending. Despite almost no change in statin utilization between 2018 and 2022, Medicaid spending on statins fell by approximately $20 million, driven by a shift from brand-name to generic formulations. Despite almost no change in statin utilization between 2018 and 2022, Medicaid spending on statins fell by approximately $20 million, driven by a shift from brand-name to generic formulations. In contrast, spending on PCSK9 inhibitors increased by $57 million as these medications became more widely used. Understanding these trends is critical as Medicaid programs work to ensure access to effective cardiovascular therapies while also identifying opportunities for cost efficiencies nationwide."

Medicaid • Reimbursement • US reimbursement • Cardiovascular

Association Between Lipoprotein(a) Levels and Incident Complex Coronary Revascularization Procedures in the FOURIER Trial (AHA 2024) - P3 | "In FOURIER, 4048 (32%) pts had a baseline Lp(a) concentration ≥125 nmol/L. A total of 332 complex coronary revascularization procedures occurred. Pts with higher baseline Lp(a) levels were more frequently female (29% vs 23%) and more likely to have multivessel disease (24% vs 21%), diabetes mellitus (38% vs 34%) or prior PCI (66% vs 60%)."

Diabetes • Metabolic Disorders

LDL-C Lowering with Evolocumab and Arterial Aneurysms: Long-Term Analysis from the FOURIER Trial (AHA 2024) - "The association between randomization to evolocumab and fewer aneurysm events was consistent for both AAA (HR 0.78 [0.56–1.09]) and non-AAA (HR 0.81 [0.55–1.18]).CONCLUSIONIn patients with stable ASCVD on optimized statin therapy, early initiation of long-term evolocumab was associated with fewer arterial aneurysm events compared with delayed initiation. These data support earlier intensive LDL-C reduction with PCSK9i as a promising strategy to prevent the formation and progression of arterial aneurysms, including AAA."

Cardiovascular

Transcriptomic Signatures and Predictors of Evolocumab Added to Maximum Statin Therapy Based on Intra-Coronary Plaque Characteristics: YELLOW III Study (AHA 2024) - "In patients with stable CAD, beneficial changes in plaque morphology after evolocumab treatment were associated with suppressed inflammation, alleviated oxidative stress and restored mitochondrial function. Transcriptomic signature of beneficial response will facilitate development of personalized therapies for treating CAD."

Inflammation • ABCA1 • ABCA13 • IL10 • IL1R2 • MMP9

Recommendations for the management of patients with type 2 diabetes at hospital discharge after an ischaemic cardiovascular event. (PubMed, Hipertens Riesgo Vasc) - "Strategies include rigorous control of lipid levels, recommending potent statins combined with ezetimibe and, if necessary, other drugs such as inclisiran, evolocumab, alirocumab, or bempedoic acid. The document emphasises the importance of education on nutrition and healthy habits, as well as the follow-up and adjustment of pharmacological treatments to achieve adequate metabolic control and reduce cardiovascular risks. Nutritional evaluation and control are essential, considering obesity as a critical factor in T2D and its association with the risk of recurrent cardiovascular events."

Clinical guideline • Journal • Review • Cardiovascular • Congestive Heart Failure • Diabetes • Dyslipidemia • Genetic Disorders • Heart Failure • Hypertension • Hypoglycemia • Metabolic Disorders • Obesity • Type 2 Diabetes Mellitus

PCSK9 Inhibitors: The Evolving Future. (PubMed, Health Sci Rep) - "In the FOURIER trial, evolocumab reduced LDL-C by 59% and major cardiovascular events by 15%-20%. The SPIRE-2 trial, despite early termination, showed a 21% risk reduction in the primary composite endpoint with bococizumab. The ODYSSEY Outcomes trial reported a 57% LDL-C reduction with alirocumab, alongside a 15% reduction in adverse events. Emerging treatments like Inclisiran offer long-term LDL-C control with fewer doses...PCSK9 inhibitors significantly lower LDL-C and reduce cardiovascular events, offering promising therapies for high-risk patients, including those with familial hypercholesterolemia (FH) and those who cannot tolerate statins. Future research will focus on optimizing these inhibitors, integrating complementary therapies, and exploring gene-editing technologies to improve patient outcomes."

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

A Phase II Study Bolstering Outcomes by Optimizing Immunotherapy Strategies With Evolocumab and Nivolumab in Patients With Metastatic Renal Cell Carcinoma (BOOST-RCC) (clinicaltrials.gov) - P2 | N=29 | Recruiting | Sponsor: M.D. Anderson Cancer Center | Trial primary completion date: Oct 2024 ➔ Oct 2026

Metastases • Trial primary completion date • Genito-urinary Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor

AMGEN REPORTS THIRD QUARTER 2024 FINANCIAL RESULTS (PRNewswire) - "Repatha (evolocumab) sales increased 40% year-over-year to $567 million in the third quarter, driven by 41% volume growth and 8% favorable changes to estimated sales deductions, partially offset by 10% lower net selling price....AMJEVITA/AMGEVITA (adalimumab) sales increased 9% year-over-year to $166 million in the third quarter....TEPEZZA (teprotumumab-trbw) generated $488 million of sales in the third quarter. TEPEZZA is the first and only FDA-approved treatment for thyroid eye disease (TED)....UPLIZNA (inebilizumab-cdon) generated $106 million of sales in the third quarter. UPLIZNA is used to treat adults with neuromyelitis optica spectrum disorder."

Sales • Cardiovascular • Crohn's disease • Dyslipidemia • Familial Hypercholesterolemia • Heterozygous Familial Hypercholesterolemia • Homozygous Familial Hypercholesterolemia • Immunology • Inflammatory Bowel Disease • Ophthalmology • Scleroderma • Systemic Sclerosis • Thyroid Eye Disease • Ulcerative Colitis

Inhibition of PCSK9 Protects against Cerebral Ischemia‒Reperfusion Injury via Attenuating Microcirculatory Dysfunction. (PubMed, Neurochem Res) - "These protective effects are speculated to be mediated through the inhibition of the ERK/NF-κB pathway. The PCSK9 inhibitor evolocumab holds promise as a therapeutic agent during the acute phase of stroke, exerting its beneficial effects by modulating the ERK/NF-κB signaling pathway."

Journal • Alzheimer's Disease • Cardiovascular • Cognitive Disorders • Ischemic stroke • Metabolic Disorders • Psychiatry • Reperfusion Injury • CLDN5 • ICAM1 • OCLN • PTPRC • VCAM1

Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) Inhibitors as Adjunct Therapy to Statins: A New Frontier in Cardiovascular Risk Reduction. (PubMed, Cureus) - "Despite concurrent statin therapy, phase 3 clinical trials have demonstrated encouraging outcomes with monoclonal antibodies against PCSK9, such as evolocumab and alirocumab, resulting in significant reductions in LDL-C levels. This study intends to investigate recent advancements in the field to evaluate PCSK9 inhibitors' safety, effectiveness, and potential for preventing CVD. The investigation will also review potential future paths and wider effects of using PCSK9 inhibitors in therapeutic settings."

Journal • Review • Cardiovascular • Dyslipidemia • Metabolic Disorders

Efficacy and safety of lipid-lowering therapies in combination with or without statin to reduce the cardiovascular risk: A systematic review of randomised controlled trials. (PubMed, Atheroscler Plus) - "We systematically reviewed randomised controlled trials (RCTs) evaluating cardiovascular outcomes associated with non-statin LLTs (bempedoic acid, alirocumab, evolocumab, ezetimibe, and inclisiran) in adults with CVD or high cardiovascular risk. The quality of the included trials was found to be fair-to-good. The systematic review findings emphasise the significance of considering non-statin LLTs as viable treatment options for individuals with CVD or high cardiovascular risk who cannot tolerate or achieve optimal lipid control with statin therapy alone."

Combination therapy • Journal • Review • Cardiovascular • Dyslipidemia

EVACS II: Evolocumab in Patients With Acute MI (clinicaltrials.gov) - P2 | N=100 | Completed | Sponsor: Johns Hopkins University | Active, not recruiting ➔ Completed

Trial completion • Acute Coronary Syndrome • Cardiovascular • Myocardial Infarction

EVACS: Evolocumab in Acute Coronary Syndrome (clinicaltrials.gov) - P2 | N=60 | Completed | Sponsor: Johns Hopkins University | Active, not recruiting ➔ Completed

Trial completion • Acute Coronary Syndrome • Cardiovascular