1-Year results from OSLER trial of anti-PCSK9 monoclonal antibody evolocumab

Mearns, Bryony M.

doi:10.1038/nrcardio.2013.201

Cited by 6 publications

(4 citation statements)

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“…Multiple-event rates were calculated as the total number of events divided by the total follow-up time at risk until the end of follow-up, and were expressed per 100 patient-years. All analyses were conducted in R version 3.2.4 software 22 .…”

Section: Statistical Considerationsmentioning

confidence: 99%

Estimated burden of cardiovascular disease and value-based price range for evolocumab in a high-risk, secondary-prevention population in the US payer context

Tóth

Danese²,

Villa

et al. 2017

Journal of Medical Economics

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Aim: To estimate real-world cardiovascular disease (CVD) burden and value-based price range of evolocumab for a US-context, high-risk, secondary-prevention population. Materials and methods: Burden of CVD was assessed using the UK-based Clinical Practice Research Datalink (CPRD) in order to capture complete CV burden including CV mortality. Patients on standard of care (SOC; high-intensity statins) in CPRD were selected based on eligibility criteria of FOURIER, a phase 3 CV outcomes trial of evolocumab, and categorized into four cohorts: high-risk prevalent atherosclerotic CVD (ASCVD) cohort (n ¼ 1448), acute coronary syndrome (ACS) (n ¼ 602), ischemic stroke (IS) (n ¼ 151), and heart failure (HF) (n ¼ 291) incident cohorts. The value-based price range for evolocumab was assessed using a previously published economic model. The model incorporated CPRD CV event rates and considered CV event reduction rate ratios per 1 mmol/L reduction in low-density lipoprotein-cholesterol (LDL-C) from a meta-analysis of statin trials by the Cholesterol Treatment Trialists Collaboration (CTTC), i.e. CTTC relationship. Results: Multiple-event rates of composite CV events (ACS, IS, or coronary revascularization) per 100 patient-years were 12.3 for the high-risk prevalent ASCVD cohort, and 25.7, 13.3, and 23.3, respectively, for incident ACS, IS, and HF cohorts. Approximately one-half (42%) of the high-risk ASCVD patients with a new CV event during follow-up had a subsequent CV event. Combining these real-world event rates and the CTTC relationship in the economic model, the value-based price range (credible interval) under a willingness-to-pay threshold of $150,000/quality-adjusted life-year gained for evolocumab was $11,990 ($9,341-$14,833) to $16,856 ($12,903-$20,678) in ASCVD patients with baseline LDL-C levels !70 mg/dL and !100 mg/dL, respectively. Conclusion: Real-world CVD burden is substantial. Using the observed CVD burden in CPRD and the CTTC relationship, the cost-effectiveness analysis showed that, accounting for uncertainties, the expected value-based price for evolocumab is higher than its current annual cost, as long as the payer discount off list price is greater than 20%. ARTICLE HISTORY

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Section: Statistical Considerationsmentioning

confidence: 99%

Estimated burden of cardiovascular disease and value-based price range for evolocumab in a high-risk, secondary-prevention population in the US payer context

Tóth

Danese²,

Villa

et al. 2017

Journal of Medical Economics

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“…More than 1,100 hypercholesterolemic participants were enrolled from the Phase II trials, and the study is planned to end in May 2016. 36 – 38 …”

Section: Clinical Efficacymentioning

confidence: 99%

“…Serious adverse events occurred in a similar percentage in patients treated with evolocumab (7.1%) and in those in the standard care group (6.3%). 37 , 38 …”

Section: Safety and Tolerability Datamentioning

confidence: 99%

Profile of evolocumab and its potential in the treatment of hyperlipidemia

Cicero¹,

Colletti²,

Borghi³

2015

DDDT

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Despite the proven efficacy of statins, they often fail to achieve low-density lipoprotein (LDL) cholesterol goals, especially in high-risk patients. Moreover, a large number of subjects cannot tolerate statins or full doses of these drugs, in particular patients with familial hypercholesterolemia. Thus, there is a need for additional effective LDL cholesterol-reducing agents. Evolocumab (AMG145) is a monoclonal antibody inhibiting proprotein convertase subtilisin/kexin type 9 that binds to the liver LDL receptor and prevents it from normal recycling by targeting it for degradation. Phase I, II, and III trials revealed that, on subcutaneous injection, either alone or in combination with statins, evolocumab is able to reduce high LDL cholesterol levels from 54% to 80%, apolipoprotein B100 from 31% to 61%, and lipoprotein(a) from 12% to 36%, in a dose-dependent manner. The incidence of side effects seems to be low and mainly limited to nasopharyngitis, injection site pain, arthralgia, and back pain. Evolocumab is an innovative powerful lipid-lowering drug, additive to statins and/or ezetimibe, with a large therapeutic range associated with a low rate of mild adverse events. If the available data are confirmed in long-term trials with strong outcome measures, evolocumab will become an essential tool in the treatment of a large number of high-risk patients, such as those affected by familial hypercholesterolemia, those who are unable to tolerate an efficacious statin dosage, and those at very high cardiovascular risk and unable to achieve their target LDL cholesterol levels with currently available lipid-lowering therapies.

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“…Evolocumab dosed every 4 weeks showed continued efficacy, safety, and tolerability over 1 year of treatment. 78,79…”

Section: Inhibition Of Pcsk9-ldl-r Interactionmentioning

confidence: 99%

Proprotein Convertase Subtilisin/Kexin 9 Inhibitors

Drăgan

Şerban

Banach

2014

J Cardiovasc Pharmacol Ther

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Proprotein convertase subtilisin/kexin 9 (PCSK9) is part of the proteinase K subfamily of subtilases and plays a key role in lipid metabolism. It increases degradation of the low-density lipoprotein receptor (LDL-R), modulates cholesterol metabolism and transport, and contributes to the production of apolipoprotein B (apoB) in intestinal cells. Exogenous PCSK9 modifies the activity of 3-hydroxy-3-methylglutaryl-coenzyme A reductase and acyl coenzyme A:cholesterol acyltransferase and enhances secretion of chylomicrons by modulating production of lipids and apoB-48. Statins increase PCSK9 messenger RNA expression and attenuate the capacity to increase LDL-R levels. Therefore, the inhibition of PCSK9 in combination with statins provides a promising approach for lowering low-density lipoprotein cholesterol (LDL-C) concentrations. This review will address new therapeutic strategies targeting PCSK9, including monoclonal antibodies, antisense oligonucleotides, small interfering RNAs, and other small molecule inhibitors. Further studies are still needed to determine the efficacy and safety of the PCSK9 inhibitors not only to decrease LDL-C but also to investigate the potential underlying mechanisms involved and to test whether these compounds actually reduce cardiovascular end points and mortality.

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1-Year results from OSLER trial of anti-PCSK9 monoclonal antibody evolocumab

Cited by 6 publications

References 1 publication

Estimated burden of cardiovascular disease and value-based price range for evolocumab in a high-risk, secondary-prevention population in the US payer context

Estimated burden of cardiovascular disease and value-based price range for evolocumab in a high-risk, secondary-prevention population in the US payer context

Profile of evolocumab and its potential in the treatment of hyperlipidemia

Proprotein Convertase Subtilisin/Kexin 9 Inhibitors

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