Repatha side effects reviews

Repatha

SIDE EFFECTS

The following adverse reactions are also discussed in other sections of the label:

  • Allergic Reactions

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.

Adverse Reactions In Adults With Primary Hyperlipidemia (including Heterozygous Familial Hypercholesterolemia)

The data described below reflect exposure to REPATHA in 8 placebo-controlled trials that included 2651 patients treated with REPATHA, including 557 exposed for 6 months and 515 exposed for 1 year (median treatment duration of 12 weeks). The mean age of the population was 57 years, 49% of the population were women, 85% White, 6% Black, 8% Asians, and 2% other races.

Adverse Reactions In A 52-Week Controlled

Trial In a 52-week, double-blind, randomized, placebo-controlled trial (Study 3 ), 599 patients received 420 mg of REPATHA subcutaneously once monthly . The mean age was 56 years (range: 22 to 75 years), 23% were older than 65 years, 52% women, 80% White, 8% Black, 6% Asian; 6% identified as Hispanic ethnicity. Adverse reactions reported in at least 3% of REPATHA-treated patients, and more frequently than in placebo-treated patients in DESCARTES, are shown in Table 1. Adverse reactions led to discontinuation of treatment in 2.2% of REPATHA-treated patients and 1% of placebo-treated patients. The most common adverse reaction that led to REPATHA treatment discontinuation and occurred at a rate greater than placebo was myalgia (0.3% versus 0% for REPATHA and placebo, respectively).

Table 1: Adverse Reactions Occurring in Greater than or Equal to 3% of REPATHA-treated Patients and More Frequently than with Placebo in DESCARTES

Adverse Reactions in Seven Pooled 12-Week Controlled Trials In seven pooled 12-week, double-blind, randomized, placebo-controlled trials, 993 patients received 140 mg of REPATHA subcutaneously every 2 weeks and 1059 patients received 420 mg of REPATHA subcutaneously monthly. The mean age was 57 years (range: 18 to 80 years), 29% were older than 65 years, 49% women, 85% White, 5% Black, 9% Asian; 5% identified as Hispanic ethnicity. Adverse reactions reported in at least 1% of REPATHA-treated patients, and more frequently than in placebo-treated patients, are shown in Table 2.

Table 2: Adverse Reactions Occurring in Greater than 1% of REPATHA-treated Patients and More Frequently than with Placebo in Pooled 12-Week Trials

Adverse Reactions In Eight Pooled Controlled Trials (Seven 12-Week Trials and One 52-Week Trial)

The adverse reactions described below are from a pool of the 52-week trial (DESCARTES) and seven 12-week trials. The mean and median exposure durations of REPATHA in this pool of eight trials were 20 weeks and 12 weeks, respectively.

Local Injection Site Reactions

Injection site reactions occurred in 3.2% and 3.0% of REPATHA-treated and placebo-treated patients, respectively. The most common injection site reactions were erythema, pain, and bruising. The proportions of patients who discontinued treatment due to local injection site reactions in REPATHA-treated patients and placebo-treated patients were 0.1% and 0%, respectively.

Allergic Reactions

Adverse Reactions In The Cardiovascular Outcomes

Trial In a double-blind, randomized, placebo-controlled cardiovascular outcomes trial (Study 1 ), 27,525 patients received at least one dose of REPATHA or placebo . The mean age was 62.5 years (range: 40 to 86 years), 45% were 65 years or older, 9% were 75 years or older, 25% women, 85% White, 2% Black and 10% Asian; 8% identified as Hispanic ethnicity. Patients were exposed to REPATHA or placebo for a median of 24.8 months; 91% of patients were exposed for ≥ 12 months, 54% were exposed for ≥ 24 months and 5% were exposed for ≥ 36 months.

The safety profile of REPATHA in this trial was generally consistent with the safety profile described above in the 12-and 52-week controlled trials involving patients with primary hyperlipidemia (including HeFH). Serious adverse events occurred in 24.8% and 24.7% of REPATHA-treated and placebo-treated patients, respectively. Adverse events led to discontinuation of study treatment in 4.4% of patients assigned to REPATHA and 4.2% assigned to placebo. Common adverse reactions (> 5% of patients treated with REPATHA and occurring more frequently than placebo) included diabetes mellitus (8.8% REPATHA, 8.2% placebo), nasopharyngitis (7.8% REPATHA, 7.4% placebo), and upper respiratory tract infection (5.1% REPATHA, 4.8% placebo).

Among the 16,676 patients without diabetes mellitus at baseline, the incidence of new-onset diabetes mellitus during the trial was 8.1% in patients assigned to REPATHA compared with 7.7% in those assigned to placebo.

Adverse Reactions In Patients With Homozygous Familial Hypercholesterolemia

Immunogenicity

As with all therapeutic proteins, there is potential for immunogenicity. The detection of antibody formation is highly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of antibody (including neutralizing antibody) positivity in an assay may be influenced by several factors including assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, comparison of the incidence of antibodies to REPATHA in the studies described below with the incidence of antibodies in other studies or to other products may be misleading.

The immunogenicity of REPATHA has been evaluated using an electrochemiluminescent bridging screening immunoassay for the detection of binding anti-drug antibodies. For patients whose sera tested positive in the screening immunoassay, an in vitro biological assay was performed to detect neutralizing antibodies.

In a pool of placebo-and active-controlled clinical trials, 0.3% (48 out of 17,992) of patients treated with at least one dose of REPATHA tested positive for the development of binding antibodies. Patients whose sera tested positive for binding antibodies were further evaluated for neutralizing antibodies; none of the patients tested positive for neutralizing antibodies.

There was no evidence that the presence of anti-drug binding antibodies impacted the pharmacokinetic profile, clinical response, or safety of REPATHA, but the long-term consequences of continuing REPATHA treatment in the presence of anti-drug binding antibodies are unknown.

Postmarketing Experience

The following additional adverse reactions have been identified during post-approval use of REPATHA. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

  • Allergic reactions: Angioedema
  • Influenza-like illness

Read the entire FDA prescribing information for Repatha (Evolocumab Injection, for Subcutaneous Injection)

Repatha®Side Effects

Important Safety Information

Do not use Repatha® if you are allergic to evolocumab or to any of the ingredients in Repatha®.

Before you start using Repatha®, tell your healthcare provider about all your medical conditions, including if you are allergic to rubber or latex, are pregnant or plan to become pregnant, or are breastfeeding or plan to breastfeed. The needle covers on the single-use prefilled syringes and the inside of the needle caps on the single-use prefilled SureClick® autoinjectors contain dry natural rubber. The single-use Pushtronex® system (on-body infusor with prefilled cartridge) is not made with natural rubber latex.

Tell your healthcare provider or pharmacist about any prescription and over-the-counter medicines, vitamins, or herbal supplements you take.

What are the possible side effects of Repatha®?

Repatha® can cause serious side effects including, serious allergic reactions. Stop taking Repatha® and call your healthcare provider or seek emergency help right away if you have any of these symptoms: trouble breathing or swallowing, raised bumps (hives), rash or itching, swelling of the face, lips, tongue, throat or arms.

The most common side effects of Repatha® include: runny nose, sore throat, symptoms of the common cold, flu or flu-like symptoms, back pain, high blood sugar levels (diabetes), and redness, pain, or bruising at the injection site.

Tell your healthcare provider if you have any side effect that bothers you or that does not go away.

These are not all the possible side effects of Repatha®. Ask your healthcare provider or pharmacist for more information. Call your healthcare provider for medical advice about side effects.

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch, or call 1-800-FDA-1088.

Please see full Prescribing Information.

PCSK9 drugs can reduce blood levels of cholesterol, which builds up in arteries (above), but only now have they been shown to prevent heart attacks and strokes.

Image Source/iStockphoto

A year and a half after its feted approval, a new cholesterol drug has passed a key test. There was no question that Repatha, an antibody drug developed by Amgen, could provide stunning drops in cholesterol for people who have already maxed out the benefits of decades-old statin drugs. But the clinical trials supporting its approval did not take the next step to show whether the therapy, known as a PCSK9 inhibitor, could actually improve or extend the lives of people taking it.

Now, those results are in. Repatha showed a measurable—if modest—benefit in reducing cardiovascular events such as heart attacks and stroke. “The open question was, ‘Does this way of lowering reduce risk of coronary heart disease,’” says Sekar Kathiresan, a cardiologist at the Massachusetts General Hospital in Boston and the Broad Institute in Cambridge, Massachusetts, who was not involved in the study. “The answer to that is a firm ‘yes.’ And that’s exciting.”

The drug reduces cholesterol—specifically, low-density lipoprotein (LDL) cholesterol that can build up in artery walls—by blocking an enzyme known as PCSK9, which would otherwise inhibit liver receptors that clear LDL cholesterol from the body. In clinical trials, both Repatha and its competitor, a drug called Praluent developed by Sanofi and Regeneron, reduced LDL cholesterol by about 60% in patients already taking statins. That was good enough for the U.S. Food and Drug Administration (FDA), which approved both drugs in 2015. (The two companies are locked in a patent dispute, in which Amgen is attempting to block Praluent from the market.)

Researchers knew there was a general relationship between cholesterol levels and cardiovascular disease risk, but “there was sort of a question of whether, when you get to very low levels, that relationship would fall off,” says William Hiatt, a physician specializing in vascular medicine at the University of Colorado in Denver and a member of an FDA advisory committee that reviewed the drugs.

Both groups launched trials to answer that question; Amgen is the first to release its findings. The company collaborated with several institutions, including Brigham and Women’s Hospital in Boston and Imperial College London, to enroll about 27,000 patients with a history of cardiovascular disease who were already taking statins. The researchers randomized patients to receive either injections of Repatha or placebo, and followed them for 2 years to track several cardiovascular events: heart attack, stroke, death, hospitalization for blocked blood flow to the heart, and stent or bypass surgery. After 2 years, 9.8% of patients in the treatment group had at least one such event, versus 11.3% in the placebo group, the team revealed today in The New England Journal of Medicine and at a meeting of the American College of Cardiology in Washington, D.C.

In other words, a physician would need to treat about 150 patients with Repatha in a year to prevent one of these bad events, Hiatt explains. “The benefit here is meaningful and substantial,” he says, “although not overwhelming.” Given that many patients at risk of a heart attack or stroke have little else to try, he says, this is “absolutely an advance in cardiovascular medicine.”

The question insurance companies are grappling with is whether that benefit justifies the list price of nearly $15,000 a year. “It’s an expensive medicine for a common disease, says Kathiresan, “and my sense is that the price will have to come down.”

Still, the result is gratifying for researchers hoping genomic studies will serve up new drugs. The drug’s mechanism of action was discovered by studying people with mutations to the gene for PCSK9 that allowed them to maintain exceptionally low cholesterol levels. “The therapies basically exactly mirror the human genetics,” Kathiresan says. “This is potentially a road map for medicines development at large.”

Patient adherence, compliance, and perspectives on evolocumab for the management of resistant hypercholesterolemia

Introduction

Extensive evidence shows that low-density lipoprotein cholesterol (LDL-C)-lowering therapy has beneficial effects in decreasing cardiovascular risk in both primary and secondary prevention.1–4

Statins are the standard of care for LDL-C lowering; however, several patients develop statin intolerance due to side effects, especially myalgias and weakness.5,6 Furthermore, even with high-intensity statin therapy, some patients cannot achieve the desired LDL-C goal, and therefore remain at high risk for cardiovascular events.7,8 Because of that, extensive research has been conducted to find additional agents with an acceptable side effect profile that could cause significant reduction of LDL-C levels.

Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors represent a relatively new class of LDL-C-lowering agents, which act by blocking the activity of PCSK9 and thus reducing the degradation of LDL receptors and increasing the clearance of LDL-C.9–11 Evolocumab is a monoclonal antibody which inhibits PCSK9 and is administered subcutaneously in biweekly or monthly intervals. In the FOURIER trial, which had a follow-up period of 2.2 years, evolocumab, when added to the statin therapy, was shown to cause an additional reduction of LDL-C levels by 59%. More importantly, evolocumab decreased the composite of cardiovascular death, myocardial infarction, or stroke by 20%.12

Notwithstanding, the benefits of the treatment with evolocumab will only be replicated in real-life if patients accept, adhere, and comply with the prescribed treatment regimen. It would be very important here to point out that in the case of statins, their real-life effectiveness is significantly compromised by poor adherence and compliance.13–15

Thus, our review aims to focus on patient adherence, compliance, and perspectives on evolocumab for the management of resistant hypercholesterolemia.

Patient adherence and compliance

Medication compliance is the act of taking medication on schedule or taking medication as prescribed; however, recently, this term has fallen into disfavor. Medication adherence is the act of filling new prescriptions or refilling prescriptions on time, and this term better represents the more complex interplay among patient, provider, and medication and reflects the fact that following a medication regimen is not necessarily a simple choice.16

The lack of adherence to cardiovascular medications in real-life settings leads to poor clinical outcomes, as it increases the risk for hospitalization and mortality, particularly in high-risk patients.17,18

With regard to statins, it is well established that statin therapy decreases mortality in high cardiovascular risk patients in both primary and secondary prevention.19,20 However, studies have reported poor adherence to statin therapy, which has been attributed to the patients’ lack of knowledge about the efficacy of the statin therapy, statin intolerance, or fear about possible side effects.21,22 Here, it has to be stressed that poor adherence and compliance to statins come with a heavy toll, as they lead to significant increases in total mortality, as well as cardiovascular morbidity and mortality.13–15

In this context, due to its acceptable side effect profile, reduced dosing frequency, and the availability of easy-to-use and effective devices for self-administration, evolocumab brings opportunities to improve the adherence to lipid-lowering therapy. Here it has to be mentioned that, in contrast to other drug classes (eg, antiplatelet agents, the effect of which is not easy to routinely monitor), monitoring of adherence to PCSK9 inhibitors is a relatively easy task in view of their profound LDL-C-lowering effect.

In this regard, studies have shown overall satisfactory results with respect to patient’s adherence to PCSK9 inhibitors (including evolocumab) in real-life settings. More specifically, in a small retrospective analysis, the level of full adherence to PCSK9 inhibitors was found to be higher than statins (79.4% vs 30.9%, respectively), although the difference did not reach statistical significance due to the small number of subjects.23 In another small study, which examined the real-world effectiveness and safety of PCSK9 inhibitors (evolocumab and alirocumab), the LDL-C reductions obtained with PCSK9 inhibitors in clinical practice were found to be similar to those described in clinical trials (50%–70%). PCSK9 inhibitors were well tolerated and there were no discontinuations due to side effects.24

Thus, based on the above, evolocumab appears to be in general well tolerated, effective, and with a low rate of reported side effects. However, in-depth patient education, close supervision, and regular follow-up are strongly recommended in order to optimize adherence and compliance to therapy.25,26

Notwithstanding, even though current studies are showing encouraging results regarding adherence to evolocumab (and PCSK9 inhibitors in general) in real-life settings, there are still insufficient data and further larger studies are needed to evaluate the short- and long-term patient adherence rates to these medications.

Acceptability and perspective on evolocumab therapy

While evolocumab is available only via subcutaneous administration, studies have revealed that the self-administration of evolocumab at home is safe and effective with the appropriate training and instructions from a health care provider. More specifically, patients were successful in self-administering evolocumab in the home-use setting in approximately 95% of attempts and achieved LDL-C reductions from baseline to week 6 or the mean of weeks 10 and 12 of approximately 65%. Rates of successful self-administration and LDL-C reduction were similar across dosing schedules and study devices.27

Furthermore, the choice of the monthly (QM) or twice weekly (Q2W) dosing regimen does not appear to be associated with any significant differences in adherence, acceptability or patients’ preferences. In a study, which included 2,318 patients (59% initially randomized to the QM regimen and 41% initially randomized to the Q2W regimen), 74% of those initially randomized to the QM regimen chose to continue with QM dosing and 26% decided to switch to the Q2W regimen. Similarly, from those initially randomized to the Q2W regimen, 70% chose to continue with Q2W dosing and 30% opted to switch to QM dosing. Only 2% of patients in the QM regimen and 2% of patients in the Q2W regimen did not receive any further doses following the first day of administration. More importantly, following initial decisions regarding dosing preference, patients did not generally choose to change their regimen further during ongoing treatment, as only 5% of QM patients and 8% of Q2W patients switched to the alternative dosing regimen.28

One of the main barriers for patient’s access and appropriate continuation of the evolocumab therapy is the difficulty in obtaining insurance coverage, which is mostly due to the high cost of the medication. Studies have indicated a mean annual wholesale price for evolocumab as high as $14,100 and have reached the conclusion that assuming 2015 prices, PCSK9 inhibitor use in patients with heterozygous familial hypercholesterolemia or atherosclerotic cardiovascular disease did not meet generally acceptable incremental cost-effectiveness thresholds and was estimated to increase US health care costs substantially.29 This was confirmed by another recent study, which showed that at current prices, the addition of PCSK9 inhibitors to statin therapy was estimated to provide an additional quality-adjusted life year for $337,729 and that significant discounts were necessary to meet conventional cost-effectiveness standards.30,31 On the other hand, the National Institute for Health and Care Excellence in the UK has approved the limited use of PCSK9 inhibitors in certain high-risk patient groups, although these National Institute for Health and Care Excellence results were based on undisclosed price discounts negotiated with the pharmaceutical companies.31,32 In a recent study, which examined the cost-effectiveness of PCSK9 inhibitors vs ezetimibe through LDL-C reductions in a Norwegian setting, it was shown that high lifetime costs of PCSK9 inhibitors may not be offset by estimated health gains for most eligible patients, and PCSK9 inhibitors were found to be cost-effective only in secondary prevention for older patients with high absolute risk of cardiovascular disease. However, the authors did point out that this picture was likely to change as price of this class of medications decreases.33 Finally, in a very recent Canadian study, despite the critical assumption that evolocumab may reduce mortality over time, it was shown that the drug was unlikely to be cost-effective for secondary prevention at current Canadian prices.34

Given the above, the treatment with evolocumab presents an initial therapy coverage denial by insurance companies as high as 80%, even when the US Food and Drug Administration-approved indications for the therapy have been met by the patient. Furthermore, only 46.6% of Medicare patients and 26.7% of privately insured patients subsequently gained approval after extensive appeals.35

In order to improve cost-effectiveness, the manufacturer of evolocumab offered a money-back guarantee by fully refunding the drug’s cost, under certain conditions, if a patient being treated with evolocumab is hospitalized with either a myocardial infarction or stroke. However, despite this improved outcomes-based pricing, the incremental cost-effectiveness ratio for a PCSK9 inhibitor added to a statin was only marginally improved. Even in the best scenario, in which the manufacturer would refund drug costs plus inpatient costs for myocardial infarction or stroke, the incremental cost-effectiveness ratio for a PCSK9 inhibitor added to a statin improved by only 3.1%.36

Conclusion and future directions

From the above data, it becomes evident that evolocumab is a promising PCSK9 inhibitor that causes significant LDL-C reductions and decreases cardiovascular risk. Although current studies are showing encouraging results regarding adherence to evolocumab in real-life settings, further larger studies are needed for a more definitive assessment of the short- and long-term patient adherence rates. In-depth patient education, close supervision, and regular follow-up are important factors to optimize adherence to therapy. Reductions in the price of evolocumab may also be necessary to improve cost-effectiveness of the drug.

Inclisiran is a long-acting small interfering RNA (siRNA) molecule directed against PCSK9, and it has been shown to significantly decrease hepatic production of PCSK9 and cause a marked reduction in LDL-C levels.37 This agent is not licensed as yet and has not been proven to reduce cardiovascular outcomes, as of now. However, inclisiran appears very promising and, in the future, if approved, its use may lead to a significant improvement in adherence and compliance due to its very infrequent, 6-monthly dosing intervals.

Disclosure

Dr Constantine E Kosmas reports personal fees from Amgen, outside the submitted work. Dr Eliscer Guzman reports personal fees from Amgen Inc., outside the submitted work. Dr Kosmas and Dr Guzman are members of the Dyslipidemia Speaker Bureau of Amgen, Inc. The authors report no other conflicts of interest in this work.

Vallejo-Vaz AJ, Robertson M, Catapano AL, et al. Low-Density Lipoprotein Cholesterol Lowering for the Primary Prevention of Cardiovascular Disease Among Men With Primary Elevations of Low-Density Lipoprotein Cholesterol Levels of 190 mg/dL or Above: Analyses From the WOSCOPS (West of Scotland Coronary Prevention Study) 5-Year Randomized Trial and 20-Year Observational Follow-Up. Circulation. 2017;136(20):1878–1891.

Reiner Ž. Statins in the primary prevention of cardiovascular disease. Nat Rev Cardiol. 2013;10(8):453–464.

Koskinas KC, Siontis GCM, Piccolo R, et al. Effect of statins and non-statin LDL-lowering medications on cardiovascular outcomes in secondary prevention: a meta-analysis of randomized trials. Eur Heart J. 2018;39(14):1172–1180.

Grundy SM. Promise of low-density lipoprotein-lowering therapy for primary and secondary prevention. Circulation. 2008;117(4):569–573.

Cohen JD, Brinton EA, Ito MK, Jacobson TA. Understanding Statin Use in America and Gaps in Patient Education (USAGE): an internet-based survey of 10,138 current and former statin users. J Clin Lipidol. 2012;6(3):208–215.

Reiner Z. Resistance and intolerance to statins. Nutr Metab Cardiovasc Dis. 2014;24(10):1057–1066.

Ridker PM, Mora S, Rose L; JUPITER Trial Study Group. Percent reduction in LDL cholesterol following high-intensity statin therapy: potential implications for guidelines and for the prescription of emerging lipid-lowering agents. Eur Heart J. 2016;37(17):1373–1379.

Wong ND, Chuang J, Wong K, Pham A, Neff D, Marrett E. Residual dyslipidemia among United States adults treated with lipid modifying therapy (data from National Health and Nutrition Examination Survey 2009–2010). Am J Cardiol. 2013;112(3):373–379.

Page MM, Watts GF. PCSK9 inhibitors – mechanisms of action. Aust Prescr. 2016;39(5):164–167.

Reiner Ž. PCSK9 inhibitors – past, present and future. Expert Opin Drug Metab Toxicol. 2015;11(10):1517–1521.

Reiner Ž. PCSK9 inhibitors in clinical practice: Expectations and reality. Atherosclerosis. 2018;270:187–188.

Sabatine MS, Giugliano RP, Keech AC, et al. FOURIER Steering Committee and Investigators. Evolocumab and Clinical Outcomes in Patients with Cardiovascular Disease. N Engl J Med. 2017;376(18):1713–1722.

Lardizabal JA, Deedwania PC. Benefits of statin therapy and compliance in high risk cardiovascular patients. Vasc Health Risk Manag. 2010;6:843–853.

Ford I, Murray H, Packard CJ, Shepherd J, Macfarlane PW, Cobbe SM. West of Scotland Coronary Prevention Study Group. Long-term follow-up of the West of Scotland Coronary Prevention Study. N Engl J Med. 2007;357(15):1477–1486.

Ho PM, Magid DJ, Shetterly SM, et al. Medication nonadherence is associated with a broad range of adverse outcomes in patients with coronary artery disease. Am Heart J. 2008;155(4):772–779.

Miller LG, Hays RD. Adherence to combination antiretroviral therapy: synthesis of the literature and clinical implications. AIDS Read. 2000;10(3):177–185.

Kolandaivelu K, Leiden BB, O’Gara PT, Bhatt DL. Non-adherence to cardiovascular medications. Eur Heart J. 2014;35(46):3267–3276.

Baroletti S, dell’orfano H. Medication adherence in cardiovascular disease. Circulation. 2010;121(12):1455–1458.

Nunes JP. Statins in primary prevention: impact on mortality. A meta-analysis study. Minerva Cardioangiol. 2017;65(5):531–538.

Rodriguez F, Maron DJ, Knowles JW, Virani SS, Lin S, Heidenreich PA. Association Between Intensity of Statin Therapy and Mortality in Patients With Atherosclerotic Cardiovascular Disease. JAMA Cardiol. 2017;2(1):47–54.

Bates TR, Connaughton VM, Watts GF. Non-adherence to statin therapy: a major challenge for preventive cardiology. Expert Opin Pharmacother. 2009;10(18):2973–2985.

Wouters H, van Dijk L, Geers HC, et al. Understanding Statin Non-Adherence: Knowing Which Perceptions and Experiences Matter to Different Patients. PLoS One. 2016;11(1):e0146272.

Gragnano F, Concilio C, Cesaro A, et al. P1513Adherence to PCSK9 inhibitors in high cardiovascular risk patients in real-world setting: results from a single-center experience and comparison with statin therapy. Eur Heart J. 2017;38(suppl_1):P1513.

Torres PR, Portilla AJ, Gonzalez MO, et al. 5PSQ-025 Real-world effectiveness and safety of evolocumab and alirocumab. Eur J Hosp Pharm. 2018;25:A176.

Saborowski M, Dölle M, Manns MP, Leitolf H, Zender S. Lipid-lowering therapy with PCSK9-inhibitors in the management of cardiovascular high-risk patients: Effectiveness, therapy adherence and safety in a real world cohort. Cardiol J. 2018;25(1):32–41.

Graesdal A, Dybvig A. Real-life PCSK9 experience: Efficacy, compliance and side effects after one year treatment in familial hypercholesterolemia patients. J Am Coll Cardiol. 2018;71(11):A1754.

Dent R, Joshi R, Stephen Djedjos C, et al. Evolocumab lowers LDL-C safely and effectively when self-administered in the at-home setting. Springerplus. 2016;5:300.

Boccara F, Dent R, Ruilope L, Valensi P. Practical considerations for the use of subcutaneous treatment in the management of Dyslipidaemia. Adv Ther. 2017;34(8):1876–1896.

Kazi DS, Moran AE, Coxson PG, et al. Cost-effectiveness of PCSK9 Inhibitor Therapy in Patients With Heterozygous Familial Hypercholesterolemia or Atherosclerotic Cardiovascular Disease. JAMA. 2016;316(7):743–753.

Arrieta A, Hong JC, Khera R, Virani SS, Krumholz HM, Nasir K. Updated Cost-effectiveness Assessments of PCSK9 Inhibitors From the Perspectives of the Health System and Private Payers: Insights Derived From the FOURIER Trial. JAMA Cardiol. 2017;2(12):1369–1374.

Kosmas CE, Dejesus E, Morcelo R, Garcia F, Montan PD, Guzman E. Lipid-lowering interventions targeting proprotein convertase subtilisin/kexin type 9 (PCSK9): an emerging chapter in lipid-lowering therapy. Drugs Context. 2017;6:212511.

National Institute for Health and Care Excellence. Evolocumab for Treating Primary Hypercholesterolaemia and Mixed Dyslipidaemia. London: National Institute for Health and Care Excellence; 2016.

Korman M, Wisløff T. Modelling the cost-effectiveness of PCSK9 inhibitors vs. ezetimibe through LDL-C reductions in a Norwegian setting. Eur Heart J Cardiovasc Pharmacother. 2018;4(1):15–22.

Lee TC, Kaouache M, Grover SA. Evaluation of the cost-effectiveness of evolocumab in the FOURIER study: a Canadian analysis. CMAJ Open. 2018;6(2):E162–E167.

Baum SJ, Toth PP, Underberg JA, Jellinger P, Ross J, Wilemon K. PCSK9 inhibitor access barriers-issues and recommendations: Improving the access process for patients, clinicians and payers. Clin Cardiol. 2017;40(4):243–254.

Kazi DS, Penko J, Ollendorf DA, Coxson PG, Bibbins-Domingo K. Effect of Money-Back Guarantees on the Cost-Effectiveness of Proprotein Convertase Subtilisin/Kexin Type 9 Inhibitors. Ann Intern Med. 2018;168(12):896–898.

Kosmas CE, Muñoz Estrella A, Sourlas A, et al. Inclisiran: A New Promising Agent in the Management of Hypercholesterolemia. Diseases. 2018;6(3):63.

How does Repatha work?

Repatha (evolocumab) is a human monoclonal antibody that works by helping the liver reduce levels of “bad” cholesterol (low-density lipoprotein, or LDL) circulating in your blood.

Repatha is the second PCSK9 inhibitor to be approved by the FDA; the first was Praluent (alirocumab). PCSK9 inhibitors are a new medication class that has been shown to greatly lower LDL (bad) cholesterol levels. PCSK9 inhibitors are known as monoclonal antibodies (MABs), a type of biologic drug. They work by inactivating a protein in the liver called proprotein convertase subtilisin kexin 9 (PCSK9). PCSK9 itself inactivates the needed receptors on the liver cell surface that transport LDL into the liver for metabolism (break down). Without these receptors, more LDL (bad cholesterol) remains in the blood. So, by inactivating PCSK9, more receptors are available to capture the bad LDL cholesterol for breakdown and removal from the blood.

Lowering the LDL in the blood is better for the heart.

See Also: PCSK9 Inhibitors: A New Class of Cholesterol Busters

Do not use Repatha® if you are allergic to evolocumab or to any of the ingredients in Repatha®.

Before you start using Repatha®, tell your healthcare provider about all your medical conditions, including if you are allergic to rubber or latex, are pregnant or plan to become pregnant, or are breastfeeding or plan to breastfeed. The needle covers on the single-use prefilled syringes and the inside of the needle caps on the single-use prefilled SureClick® autoinjectors contain dry natural rubber. The single-use Pushtronex® system (on-body infusor with prefilled cartridge) is not made with natural rubber latex.

Tell your healthcare provider or pharmacist about any prescription and over-the-counter medicines, vitamins, or herbal supplements you take.

What are the possible side effects of Repatha®?

Repatha® can cause serious side effects including, serious allergic reactions. Stop taking Repatha® and call your healthcare provider or seek emergency help right away if you have any of these symptoms: trouble breathing or swallowing, raised bumps (hives), rash or itching, swelling of the face, lips, tongue, throat or arms.

The most common side effects of Repatha® include: runny nose, sore throat, symptoms of the common cold, flu or flu-like symptoms, back pain, high blood sugar levels (diabetes), and redness, pain, or bruising at the injection site.

Tell your healthcare provider if you have any side effect that bothers you or that does not go away.

These are not all the possible side effects of Repatha®. Ask your healthcare provider or pharmacist for more information. Call your healthcare provider for medical advice about side effects.

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch, or call 1-800-FDA-1088.

Please see full Prescribing Information.

Amgen cholesterol drug reduces artery-clogging plaque in study

NEW ORLEANS (Reuters) – Amgen Inc’s potent new drug Repatha, when added to statin therapy, not only took “bad” LDL cholesterol down to extremely low levels but caused declines in artery-clogging plaque in a majority of high-risk heart patients after 18 months of treatment, according to data from a clinical trial.

An Amgen sign is seen at the company’s office in South San Francisco, California in this October 21, 2013 file photo. REUTERS/Robert Galbraith/Files

Amgen had previously announced the study was a success. But the percentage of patients who experienced a decrease of the substance that is the underlying cause of heart disease and magnitude of plaque regression was revealed at the American Heart Association scientific meeting in New Orleans on Tuesday.

The 968-patient trial compared the effect of monthly injections with Repatha plus a cholesterol-lowering statin with statins alone on the plaques that can break off and cause heart attacks. The plaque measurements were collected with an ultrasound probe placed inside the diseased artery.

Patients in the study had symptomatic heart disease and blockages of 20 percent to 50 percent in the tested artery.

“We saw profound regression,” said Dr. Steven Nissen, head of cardiology at Cleveland Clinic who presented the data.

The combination therapy led to a further 60 percent reduction in LDL levels beyond statins alone to an average LDL of a mere 36.6. That translated into a decrease in percent of blockage volume of about 1 percent compared with no change for statins alone.

In all, 64.3 percent on the combination therapy experienced plaque regression compared with 52.7 percent with statin monotherapy.

“We didn’t know what would happen to disease progression at LDL cholesterol levels when we go to below about 60,” Nissen explained.

For those who began the trial with LDL below 70, the lowest target guideline for high risk patients, 81 percent experienced coronary plaque regression with the addition of Repatha compared with 48 percent for statins alone. Those Repatha patients on average saw LDL levels drop to 24 with a low of about 15.

“That’s unbelievable. So when you get down to 24 you’ve got a really high chance of your plaques melting away,” Nissen said.

Repatha and Praluent from Regeneron Pharmaceuticals and Sanofi belong to an expensive new class of drugs known as PCSK9 inhibitors. They carry a list price of more than $14,000 a year before discounts and rebates.

Many heart doctors have been upset by barriers to access to these drugs they encounter from health insurers and pharmacy benefit managers, even for their sickest patients who meet all the criteria mandated by the U.S. Food and Drug Administration.

More than 100,000 prescriptions have been written for Repatha in the United States since its approval, but two-thirds of patients are ultimately denied, Amgen said.

“It’s crazy what’s going on. They’ve basically destroyed our capacity to treat our patients with the drugs that we need to treat them with,” said Dr. Seth Baum, president of the American Society for Preventive Cardiology.

In the third quarter, Repatha had anemic sales of just $40 million, while Praluent took in $38 million for drugs forecast to be multibillion-dollar products.

It is widely believed that payers will not lift reimbursement restrictions until they see results from huge studies designed to show that the new medicines cut the risk of heart attacks and death in addition to their ability to slash LDL levels. The Repatha outcomes data is expected in early 2017.

But the plaque regression data unveiled on Tuesday is likely a strong indictor that those trials will be positive.

“These findings suggest that the large clinical outcome trials currently underway are likely to show major benefits,” said Dr. Stephen Nicholls, one of the study’s lead directors.

Reporting by Bill Berkrot; Editing by Chizu Nomiyama

Our Standards:The Thomson Reuters Trust Principles.

About the author

Leave a Reply

Your email address will not be published. Required fields are marked *