News
News on UK NICE appraisals – evolocumab and alirocumab
The UK National Institute for Health and Clinical Excellence (NICE) issued draft guidance for evolocumab and alirocumab this week. Here PCSK9 Forum reports these preliminary decisions and draft guidance for each. However, we must reiterate that both are draft and open to consultation until finalization…
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Evolocumab first PCSK9 inhibitor licensed in Japan
The Japanese Ministry of Health, Labour and Welfare has approved evolocumab (Repatha) for the treatment of patients with familial hypercholesterolemia (FH, inherited high cholesterol) or hypercholesterolaemia who are at high risk of cardiovascular events and do not adequately respond to statins. Approval was supported by…
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LY3015014: Another PCSK9 monoclonal enters the arena
Hot on the heels of alirocumab, evolocumab and bococizumab, comes the next PCSK9 monoclonal antibody, LY3015014. In this aaleport, dosing every 4 weeks with LY3015014 resulted in about 50% reduction in LDL cholesterol, comparable to that observed with these other monoclonal antibodies. LY3015014 is a…
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Looking back at 2015: what made the news?
PCSK9 Forum Editors pick the highlights of PCSK9 and cholesterol research No. 1. The promise of PCSK9 inhibition may deliver in reducing cardiovascular outcomes. In concomitant reports, treatment with alirocumab or evolocumab, on top of conventional lipid lowering therapy including statin, resulted in consistent lowering…
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PCSK9 inhibitors: What is the value of addressing unmet clinical needs in LDL management?
No doubt the PCSK9 monoclonal antibodies are effective in lowering LDL cholesterol across the spectrum of high cardiovascular risk patients. Moreover, data from a recent meta-analysis looking at clinical outcomes with these novel treatments suggested a 50% reduction in all-cause mortality and myocardial infarction (1)….
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Study questions utility of measuring PCSK9 in ACS setting
High PCSK9 levels at angiography were not predictive of 1-year mortality in patients with acute coronary syndrome (ACS), but did predict failure to attain LDL cholesterol goal at 1 year follow-up, independent of lipid-modifying therapy or baseline LDL cholesterol levels. This study measured PCSK9 levels…
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Making Familial Hypercholesterolaemia visible
Image courtesy of the FH Foundation www.thefhfoundation.org
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HEART UK responds to NICE preliminary decision on evolocumab
HEART UK, the Cholesterol Charity, has voiced concerns about the preliminary decision by the UK National Institute for Health and Care Excellence (NICE) against the use of evolocumab (Repatha) as a therapeutic option for management of hypercholesterolaemia and mixed dyslipidaemia. In particular, HEART UK makes…
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Norwegian study: Need for improved familial hypercholesterolaemia care in post-statin era
Familial hypercholesterolaemia (FH) is the most common inherited cause of premature coronary heart disease (CHD), affecting about 1 in 200 people worldwide (1). Recent studies have also highlighted an increased risk of other cardiovascular disease, including peripheral artery disease in FH subjects (2). Considering the…
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Preliminary decision on NHS use of evolocumab (Repatha)
In preliminary guidelines released this morning, the UK National Institute for Health and Care Excellence (NICE) has decided against the use of evolocumab (Repatha) as a therapeutic option for management of hypercholesterolaemia and mixed dyslipidaemia. The lack of definitive evidence that evolocumab reduces cardiovascular events,…
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Benefit of PCSK9 inhibitors in primary hypercholesterolaemia
This meta-analysis including more than 13,000 patients showed that PCSK9 inhibitors result in superior lipid lowering compared with ezetimibe in patients with primary hypercholesterolaemia, and this is likely to translate to improved clinical outcomes. This study evaluated summarized information comparing the impact of PCSK9 inhibitors…
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Alirocumab: no impact on glycaemic control
The majority of high cardiovascular risk patients are already on statins (with or without other lipid modifying therapy). Given the small risk of incident diabetes associated with statin therapy (1), a key question is whether PCSK9 inhibition exacerbates this risk. However, pooled analyses of more…
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ALN-PCSsc data suggest 6-month dosing
There was more news from the Phase I trial of ALN-PCSsc, an investigational RNAi therapeutic targeting PCSK9, presented at the last Latebreaker Clinical Trials session. Following initial results, presented at the European Society of Cardiology Congress, London, data reported at the American Heart Association Scientific…
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PCSK9 gain-of-function variants associated with higher triglycerides
The role of PCSK9 in regulating LDL receptor levels is well established. However, this study also adds to evidence implicating PCSK9 in control of very low-density lipoprotein (VLDL) metabolism. In this study, 940 clinically diagnosed familial hypercholesterolaemia (FH) heterozygotes were investigated for carriage of the…
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No link between low LDL-C and dementia
Results from this Mendelian randomisation study do not show any association between exposure to low LDL cholesterol levels and risk of dementia. The study used a number of genetic variants known to be involved with LDL cholesterol synthesis and metabolism: hydroxy-3-methylglutaryl-CoA reductase (HMGCR); rs17238484, and…
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Evolocumab: Higher doses, less variability in LDL response
The approval of the PCSK9 monoclonal antibodies offers a novel approach to addressing unmet clinical needs in high cardiovascular risk patients. However, because evolocumab is offered as either 2-weekly or monthly dose regimens further information is needed so clinicians can make the right decision regarding…
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Hope for a small molecule PCSK9 inhibitor?
Current developments aimed at targeting PCSK9 have predominantly focused on monoclonal antibody therapies, or latterly on inhibiting synthesis of this protein with RNA interference approaches. However, is there a possibility for a small molecule antagonist of PCSK9? Results from this experimental study suggests potential in…
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ODYSSEY trials analysis: Alirocumab 75 mg 2-weekly adequate in most patients
One question from the phase III trials with the PCSK9 monoclonal antibody alirocumab is how many high cardiovascular risk patients require uptitration. Results from an analysis of more than 1200 patients included in 6 Phase III trials from the ODYSSEY programme show that most attained…
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Benefit of alirocumab in moderate chronic kidney disease
Patients with chronic kidney disease (CKD) represent an important high cardiovascular risk group, especially in view of evidence that the prevalence of this condition is increasing rapidly world-wide. Statins with minimal renal excretion are the treatment of choice for management of the associated dyslipidaemia; however,…
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Need to manage lipoprotein(a), blood pressure and renal insufficiency in familial hypercholesterolaemia
This study makes the case for identifying and managing elevated lipoprotein(a), high blood pressure, and renal insufficiency, to reduce the risk of premature coronary artery disease (CAD) in patients with familial hypercholesterolaemia (FH, inherited high cholesterol). Elevated lipoprotein(a) [Lp(a)] is already recognised as causal for…
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