Clinical Equivalence of Evolocumab Among Patient Subgroups in Proficio: A Pooled Analysis of 3146 Patients From Phase 3 Studies

Stroes, ES; Robinson, J; Raal, Frederick J.; Dufour, Robert; Sullivan, David; Blagden, Mark; Yang, Jing; Wasserman, Scott M.; Koren, Michael

doi:10.1016/j.cjca.2015.07.619

Cited by 3 publications

(4 citation statements)

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“…Goal achievement in patients with diabetes was high, with 87–88% of patients achieving LDL‐C levels below 1.8 mmol l –1 (70 mg dl −1 ) . A second pooled analysis of four Phase 3 trials also found that evolocumab reduced LDL‐C to a similar extent in patients with and without type 2 diabetes .…”

Section: Resultsmentioning

confidence: 95%

“…Finally, a pooled analysis of four Phase 3 studies found that evolocumab reduced LDL‐C regardless of age, gender, presence of metabolic syndrome and cardiovascular risk level .…”

Section: Resultsmentioning

confidence: 99%

“…The efficacy of alirocumab does not appear to be influenced by age, body mass index, intensity of statin treatment or baseline levels of LDL‐C, HDL cholesterol (HDL‐C) or triglycerides . The starting dose of evolocumab for adults with primary hypercholesterolaemia or mixed dyslipidaemia is also based on clinical trial data and is either 140 mg Q2W or 420 mg Q4W; the two doses are clinically equivalent . For those with HoFH, 420 mg Q4W is recommended initially, with up‐titration to 420 mg Q2W if a clinically meaningful response is not achieved after 12 weeks .…”

Section: Introductionmentioning

confidence: 99%

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Systematic review of published Phase 3 data on anti‐PCSK9 monoclonal antibodies in patients with hypercholesterolaemia

Gouni‐Berthold

Descamps

Fraass

et al. 2016

Brit J Clinical Pharma

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AimsTwo anti‐proprotein convertase subtilisin/kexin type 9 (PCSK9) monoclonal antibodies, alirocumab and evolocumab, have been approved for the treatment of hypercholesterolaemia in certain patients. We reviewed data from Phase 3 studies to evaluate the efficacy and safety of these antibodies.MethodsWe systematically reviewed Phase 3 English‐language studies in patients with hypercholesterolaemia, published between 1 January 2005 and 20 October 2015. Congress proceedings from 16 November 2012 to 16 November 2015 were also reviewed.ResultsWe identified 12 studies of alirocumab and nine of evolocumab, including over 10 000 patients overall. Most studies enrolled patients with hypercholesterolaemia and used anti‐PCSK9 antibodies with statins. The ODYSSEY FH I, FH II and HIGH FH alirocumab studies and the RUTHERFORD‐2 evolocumab study exclusively recruited patients with heterozygous familial hypercholesterolaemia. Two evolocumab studies focused mainly on homozygous familial hypercholesterolaemia (HoFH): TESLA Part B and TAUSSIG (a TESLA sub‐study); only those data for HoFH are reported here. All comparator studies demonstrated a reduction in LDL cholesterol (LDL‐C) with the anti‐PCSK9 antibodies. No head‐to‐head studies were conducted between alirocumab and evolocumab. Up to 87% of patients receiving alirocumab and up to 98% receiving evolocumab reached LDL‐C goals. Both antibodies were effective and well tolerated across a broad population of patients and in specific subgroups, such as those with type 2 diabetes.ConclusionsUsing anti‐PCSK9 antibodies as add‐on therapy to other lipid‐lowering treatments or as monotherapy for patients unable to tolerate statins may help patients with high cardiovascular risk to achieve their LDL‐C goals.

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Section: Resultsmentioning

confidence: 95%

“…Finally, a pooled analysis of four Phase 3 studies found that evolocumab reduced LDL‐C regardless of age, gender, presence of metabolic syndrome and cardiovascular risk level .…”

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Systematic review of published Phase 3 data on anti‐PCSK9 monoclonal antibodies in patients with hypercholesterolaemia

Gouni‐Berthold

Descamps

Fraass

et al. 2016

Brit J Clinical Pharma

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“…Patients with mixed dyslipidemia who were treated with evolocumab 140 mg every 2 weeks (Q2W) or 420 mg once every month (QM) from three completed phase 3 evolocumab trials of 12-week duration were included in the analysis [ 31 – 33 ]. Evolocumab biweekly and monthly doses have shown clinical equivalence [ 34 ]. The MENDEL-2 trial evaluated the safety and efficacy of evolocumab monotherapy versus placebo or ezetimibe on LDL-C reduction in patients with a 10-year Framingham risk score of ≤ 10% (NCT01763827) [ 31 ].…”

Section: Methodsmentioning

confidence: 99%

Effects of Evolocumab on the ApoA1 Remnant Ratio: A Pooled Analysis of Phase 3 Studies

May

Muhlestein

et al. 2019

Cardiol Ther

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Introduction The apolipoprotein A1 (apoA1) remnant ratio has been identified as an independent cardiovascular (CV) risk factor. Higher apoA1 remnant ratios may predict lower CV risk in some patients. This analysis aimed to evaluate the effects of evolocumab on the change from baseline in the apoA1 remnant ratio compared with placebo. Methods This pooled post hoc analysis included 2464 patients with mixed dyslipidemia treated with evolocumab 140 mg every 2 weeks (Q2W) or 420 mg once monthly (QM) in three phase 3 evolocumab trials. The apoA1 remnant ratio was calculated by dividing apoA1 by the difference between non-high-density lipoprotein cholesterol (non-HDL-C) and low-density lipoprotein cholesterol (LDL-C). ApoA1 remnant ratio strata were generated using previously published tertile (< 4.7, 4.7–6.8, and > 6.8) and partitioning categories (< 3.6, 3.6–6.0, and > 6.0). Results The baseline apoA1 remnant ratio in evolocumab and placebo treatment arms was 7.1 and 7.3, respectively. At week 12, evolocumab 140 mg Q2W and 420 mg QM increased the apoA1 remnant ratio by 25.0% and 33.6%, respectively, versus placebo ( p < 0.0001 for both groups). When patients were categorized by week 12 apoA1 remnant ratio thresholds (< 3.6 vs. > 3.6, and < 4.7 vs. > 4.7), those with higher week 12 apoA1 remnant ratios were significantly more likely to have also achieved a target non-HDL-C level of < 100 mg/dl. In the subset of women > 50 years of age, the proportion of patients at apoA1 remnant ratio thresholds < 3.6, 3.6–6.0, and > 6.0 at baseline shifted toward or remained at higher thresholds at week 12. Conclusions This post hoc analysis suggests that evolocumab increases the apoA1 remnant ratio. Funding Amgen Inc. Plain Language Summary Plain language summary available for this article. Electronic supplementary material The online version of this article (10.1007/s40119-019-0133-6) contains supplementary material, which is available to authorized users.

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A Comparison of Ezetimibe and Evolocumab for Atherogenic Lipid Reduction in Four Patient Populations: A Pooled Efficacy and Safety Analysis of Three Phase 3 Studies

et al. 2020

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Introduction Clinicians, payers, guideline committees, and policymakers support the use of high-intensity statins in patients at high risk for complications of cardiovascular disease (CVD). Guidelines and recommendations provide guidance on next steps for patients with inadequate low-density lipoprotein cholesterol (LDL-C) control on maximally tolerated statin or for those who are statin-intolerant. Ezetimibe and evolocumab improve CV outcomes when added to statins in high-CV-risk populations. The aim of the study was to compare evolocumab and ezetimibe for lipid-lowering efficacy and safety. Methods We summarized data from 1427 patients from three phase 3 evolocumab studies comparing double-blinded evolocumab vs. ezetimibe. These studies evaluated four distinct populations: those free of CVD receiving each agent as monotherapy, patients with CVD receiving add-on therapy to low- or high-intensity statin, and statin-intolerant patients. Lipid efficacy and safety were reported at week 12. Results Across the studies, evolocumab reduced LDL-C by a mean 55–61% from baseline to week 12; ezetimibe lowered LDL-C by 18–20% from baseline (mean difference = 38–43% favoring evolocumab; p < 0.0001). This corresponded to absolute reductions in LDL-C of 60–104 mg/dL with evolocumab vs. 17–35 mg/dL with ezetimibe. Evolocumab also significantly improved other lipids and led to a higher percentage of patients achieving LDL-C goals vs. ezetimibe. Adverse events and discontinuation rates (oral and parenteral therapy) were balanced across groups, suggesting good tolerance and acceptance of both treatments. Conclusions Evolocumab outperformed ezetimibe in efficacy and lipid goal attainment. Both products demonstrated good safety/tolerability. These data may help guide access decisions for high-risk patients with inadequate treatment response or intolerance to statin therapy.

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Clinical Equivalence of Evolocumab Among Patient Subgroups in Proficio: A Pooled Analysis of 3146 Patients From Phase 3 Studies

Cited by 3 publications

References 0 publications

Systematic review of published Phase 3 data on anti‐PCSK9 monoclonal antibodies in patients with hypercholesterolaemia

Systematic review of published Phase 3 data on anti‐PCSK9 monoclonal antibodies in patients with hypercholesterolaemia

Effects of Evolocumab on the ApoA1 Remnant Ratio: A Pooled Analysis of Phase 3 Studies

A Comparison of Ezetimibe and Evolocumab for Atherogenic Lipid Reduction in Four Patient Populations: A Pooled Efficacy and Safety Analysis of Three Phase 3 Studies

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