DOCSLIB.ORG

Bempedoic Acid: a Novel LDL Cholesterol–Lowering Agent Kylee Shriver

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Bempedoic Acid: a Novel LDL Cholesterol–Lowering Agent Kylee Shriver CLINICAL PHARMACOLOGY UPDATE Bempedoic Acid: A Novel LDL Cholesterol–Lowering Agent Kylee Shriver Hypercholesterolemia is commonly associated with di- of bempedoic acid/ezetimibe combination products. A abetes. In combination with diabetes, it puts patients at cardiovascular outcomes trial of bempedoic acid is an increased risk for premature coronary heart disease ongoing (NCT02993406). This agent is the first oral and atherosclerosis (1). adenosine triphosphate citrate lyase (ACL) inhibitor for LDL cholesterol–lowering. Lipoproteins are developed in one of two ways, via the exogenous or endogenous pathways. LDL cholesterol is a product of VLDL metabolism via the endogenous pathway. Indication Levels of LDL in the plasma are determined by the rate of Bempedoic acid is to be used as adjunctive therapy to LDL production and clearance. The LDL production rate diet and maximally controlled statin therapy for the from VLDL depends on LDL receptor activity. High re- treatment of heterozygous familial hypercholesterolemia ceptor activity leads to a decrease in LDL production. or established atherosclerotic cardiovascular disease in Alternatively, low LDL receptor activity leads to an in- adults who require additional LDL cholesterol–lowering crease in LDL production. These levels of receptors in the therapies (4). The effect of bempedoic acid on liver are regulated by the cholesterol content of the cardiovascular morbidity and mortality has not hepatocytes. If the content is low, LDL receptor activity been determined. increases to allow for the increased uptake of cholesterol. If the content is higher, LDL receptor activity is decreased, and the LDL uptake is diminished (2). Mechanism of Action Many medications are available today to manage hy- Bempedoic acid inhibits ACL, an enzyme that is upstream percholesterolemia. The most commonly used are statins, from HMG-CoA reductase in the cholesterol synthesis fibrates, bile acid sequestrants, niacin, and dietary cho- pathway. Bempedoic acid and its active metabolite, lesterol uptake inhibitors. Less commonly used therapies ESP15228, require CoA activation via very-long-chain for cholesterol management include PCSK9 (proprotein acyl-CoA synthetase 1 (ACSVL1) to ETC-1002-CoA and convertase subtilisin/kexin type 9) inhibitors, MTP ESP15528-CoA. ASCVL1 is primarily expressed in the liver (microsomal triglyceride transfer protein) inhibitors, and is not activated in the skeletal muscle (5). Inhibition of CETP (cholesteryl ester transfer protein) inhibitors, and ACL by ETC-1002-CoA results in decreased cholesterol synthesis in the liver and decreases LDL cholesterol in apolipoprotein B-100 antisense oligonucleotides. None of plasma via upregulation of LDL receptors (4,5). these therapies have the same mechanism of action as the novel therapy bempedoic acid (Esperion Therapeutics). Bempedoic acid has been shown to significantly lower LDL Potential Advantages cholesterol levels when added to maximally tolerated The main advantage of bempedoic acid is its novel statin therapies compared with placebo (3). Recently, mechanism. As the first drug of its kind, it allows patients bempedoic acid has been approved by the U.S. Food and the opportunity to try to optimize their therapy via a novel Drug Administration (FDA). The manufacturer has also mechanism before transitioning to the more invasive, submitted new drug applications (NDAs) and marketing injectable agents such as PCSK9 inhibitors. During the authorization applications (MMAs) seeking FDA approval CLEAR Wisdom (Evaluation of Long-Term Efficacy of Washington State University Corresponding author: Kylee Shriver, [email protected] https://doi.org/10.2337/cd20-0038 ©2020 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. More information is available at https://www.diabetesjournals.org/content/license. 1 Clinical Diabetes Online Ahead of Print, published online August 7, 2020 CLINICAL PHARMACOLOGY UPDATE Bempedoic Acid (ETC-1002) in Patients With Hyperlip- gout. Uric acid levels should be monitored and urate- idemia at High Cardiovascular Risk) and CLEAR lowering therapies should be initiated as appropriate. Harmony (Evaluation of Long-Term Safety and Tolera- Tendon rupture was also observed during trials (in 0.5% bility of ETC-1002 in High-Risk Patients With Hyper- of patients); thus, bempedoic acid should be avoided in lipidemia and High CV Risk) trials (6), the LDL those with a known history of tendon disorders or cholesterol–lowering capability of bempedoic acid was ruptures (4). significant. At week 12, bempedoic acid decreased levels Some other side effects noticed with bempedoic acid by 15.1% compared with a 2.4% increase with placebo. In during trials were upper respiratory tract infections (in participants not on statin therapy, bempedoic acid low- 4.5%), muscle spasms (in 3.6%), and back pain (in 3.3%), ered LDL cholesterol by 24.6% compared with 2.6% in the as well as abdominal pain, bronchitis, pain in extremities, placebo group; when used in combination with high- anemia, and elevated liver enzymes in smaller fractions of intensity statin therapy, bempedoic acid reduced trial participants (4). LDL levels by 14.4% compared with a 2.8% decrease in placebo. These effects were sustained for at least 52 weeks, making long-term therapy a possible option. Cost In addition to lowering LDL cholesterol levels, bempedoic It is estimated that bempedoic acid will cost ~ $300/ fi acid was shown to signi cantly decrease total cholesterol month ($10/day) for 180 mg tablets taken once daily as by 9.9% compared with an increase of 1.3% with placebo. directed. Although this can be considered a hefty price for This treatment could be a more attractive options for most patients, there is a manufacturer’s coupon available ’ prescribers if the goal is to lower a patient s total and LDL offering some cost savings (7). Although it is a newly ’ – cholesterol levels. Although it s LDL cholesterol lowering approved drug, its price is lower than expected for a capability is not as good as that of PCSK9 inhibitors, novel agent. it is cheaper and is an oral option, so no injections are necessary. Another advantage of bempedoic acid is that it was Commentary designed specifically to avoid myalgias, one of the side Bempedoic acid is the first ACL inhibitor for use as an LDL effects of statin use. Many patients requiring dual therapy cholesterol–lowering therapy. Many trials, most notably for hypercholesterolemia are on agents in combinations the CLEAR Wisdom and CLEAR Harmony trials, have with statins that can increase the risk for myalgias and proven the efficacy of bempedoic acid in lowering LDL rhabdomyolysis. Although it works on the same choles- cholesterol levels when used in conjunction with maxi- terol pathway as statins, its active metabolite is not mized statin therapy. This novel treatment offers a new present in skeletal muscles; therefore, the myalgia risk is option for patients and providers when trying to optimize eliminated (6). cholesterol-lowering therapy. Pending NDAs and MAAs for combinations of bempedoic acid and ezetimibe could provide even more options. Potential Disadvantages Although its primary use will be in conjunction with statin therapy, bempedoic acid cannot be administered with Bottom Line doses of simvastatin .20 mg or pravastatin doses .40 mg. Bempedoic acid is an attractive adjunctive therapy for LDL Exceeding these doses can result in higher concentrations cholesterol–lowering in adults. Additionally, its design of statin and increase the risk of myopathies. Also, it helps to avoid myalgia risk, and its oral administration has been shown that the LDL cholesterol–lowering makes it potentially easier to use than injectable capability of bempedoic acid decreases as statin intensity PSCK9 inhibitors. Finally, it can potentially offer a is increased (6). cost advantage when compared with other injectable During trials, bempedoic acid was associated with ele- options when additional LDL cholesterol control vations in serum uric acid (in 1.5% of patients), causing is needed. new-onset gout or precipitating gout flares in patients with preexisting gout. Because of this potential DUALITY OF INTEREST adverse effect, bempedoic acid should be used with No potential conflicts of interest relevant to this article were caution in patients with known hyperuricemia or reported. 2 CLINICAL.DIABETESJOURNALS.ORG Clinical Diabetes Online Ahead of Print, published online August 7, 2020 SHRIVER GUARANTOR AUTHOR 4. Nexletol [package insert]. Ann Arbor, MI, Esperion Thera- As the sole author, K.S. is the guarantor of this work and, as such, peutics Inc., 2020 had full access to all of the references cited and takes re- 5. Esperion Therapeutics. Bempedoic acid: a novel agent. sponsibility for the accuracy of the content. Available from https://www.esperion.com/science/bempedoic- acid. Accessed 10 April 2020 REFERENCES 6. Mao J, Blumenthal R, Martin SS. Bempedoic acid, the next LDL cholesterol-lowering medication to join the 1. American Heart Association. Cholesterol abnormalities and arsenal? Insights from the CLEAR Wisdom trial. Available diabetes. Available from https://www.heart.org/en/health-topics/ from https://www.acc.org/latest-in-cardiology/articles/ – diabetes/why-diabetes-matters/cholesterol-abnormalities 2019/05/03/10/20/bempedoic-acid-the-next-ldl-cholesterol- diabetes. Accessed 10 April 2020 lowering-medication-to-join-the-arsenal. Accessed 10 2. Feingold KR, Grunfeld C. Introduction to lipids and lioproteins. April 2020 Available from https://www.endotext.org. Accessed 10 April 7. Vinluan F. Esperion’s FDA-approved cholesterol drug 2020 priced even lower than expected. Available from https:// 3. Ray KK, Bays HE, Catapano AL, et al.; CLEAR Harmony xconomy.com/detroit-ann-arbor/2020/02/24/esperions-fda- Trial. Safety and efficacy of bempedoic acid to reduce LDL approved-cholesterol-drug-priced-even-lower-than-expected. cholesterol. N Engl J Med 2019;380:1022–1032 Accessed 10 April 2020 3 Clinical Diabetes Online Ahead of Print, published online August 7, 2020.
Load more

Recommended publications
  • Nustendi, INN-Bempedoic Acid, Ezetimibe
    Summary of risk management plan for Nustendi (Bempedoic acid/Ezetimibe) This is a summary of the risk management plan (RMP) for Nustendi. The RMP details important risks of Nustendi, how these risks can be minimized, and how more information will be obtained about Nustendi's risks and uncertainties (missing information). Nustendi's summary of product characteristics (SmPC) and its package leaflet give essential information to healthcare professionals and patients on how Nustendi should be used. This summary of the RMP for Nustendi should be read in the context of all this information, including the assessment report of the evaluation and its plain-language summary, all which is part of the European Public Assessment Report (EPAR). Important new concerns or changes to the current ones will be included in updates of Nustendi's RMP. I. The Medicine and What It Is Used For Nustendi is authorized for treatment of primary hypercholesterolemia in adults, as an adjunct to diet (see SmPC for the full indication). It contains bempedoic acid as the active substance and it is given by mouth. Further information about the evaluation of Nustendi’s benefits can be found in Nustendi’s EPAR, including in its plain-language summary, available on the EMA website, under the medicine’s webpage https://www.ema.europa.eu/en/medicines/human/EPAR/nustendi II. Risks Associated With the Medicine and Activities to Minimize or Further Characterize the Risks Important risks of Nustendi, together with measures to minimize such risks and the proposed studies for learning
    [Show full text]
  • Bempedoic Acid
    Drug Therapy Guidelines Bempedoic Acid (Nexletol [bempedoic acid], Nexlizet [bempedoic acid, ezetimibe]) Applicable Medical Benefit Effective: 5/28/2021 Pharmacy- Formulary 1 x Next Review: 3/23 Pharmacy- Formulary 2 x Date of Origin: 4/23/20 Pharmacy- Formulary 3/Exclusive x Review Dates: 3/20, 3/21 Pharmacy- Formulary 4/AON x I. Medication Description Bempedoic acid is an adenosine triphosphate-citrate lyase (ACL) inhibitor that lowers low-density lipoprotein cholesterol (LDL-C) through inhibition of cholesterol synthesis in the liver. Bempedoic acid, an inactive prodrug, and its active metabolite, ESP15228, require coenzyme A (CoA) activation within the liver by very-long-chain acyl CoA synthetase-1 (ACSVL1) to form bempedoic acid-CoA (ETC-1002-CoA) and ESP15228-CoA, respectively. ACSVL1 is primarily expressed in the liver and is absent in adipose tissue and muscles. ACL is an important enzyme that links carbohydrate metabolism to the pathways for cholesterol and fatty synthesis within the liver. Specifically, ACL catalyzes the cleavage of citrate to acetyl-CoA and oxaloacetate within the cholesterol synthesis pathway and is located upstream from HMG-CoA reductase. Both oxaloacetate and acetyl-CoA are important substrates in the synthesis of cholesterol and fatty acids. Thus, inhibition of ACL by bempedoic acid decreases cholesterol and fatty acid synthesis resulting in the upregulation of LDL-C receptors, increased uptake of LDL-C by the liver and reduced blood LDL-C levels. Ezetimibe reduces blood cholesterol by inhibiting the absorption of cholesterol by the small intestine. The molecular target of ezetimibe has been shown to be the sterol transporter, Niemann-Pick C1-Like 1 (NPC1L1), which is involved in the intestinal uptake of cholesterol and phytosterols.
    [Show full text]
  • Classification Decisions Taken by the Harmonized System Committee from the 47Th to 60Th Sessions (2011
    CLASSIFICATION DECISIONS TAKEN BY THE HARMONIZED SYSTEM COMMITTEE FROM THE 47TH TO 60TH SESSIONS (2011 - 2018) WORLD CUSTOMS ORGANIZATION Rue du Marché 30 B-1210 Brussels Belgium November 2011 Copyright © 2011 World Customs Organization. All rights reserved. Requests and inquiries concerning translation, reproduction and adaptation rights should be addressed to [email protected]. D/2011/0448/25 The following list contains the classification decisions (other than those subject to a reservation) taken by the Harmonized System Committee ( 47th Session – March 2011) on specific products, together with their related Harmonized System code numbers and, in certain cases, the classification rationale. Advice Parties seeking to import or export merchandise covered by a decision are advised to verify the implementation of the decision by the importing or exporting country, as the case may be. HS codes Classification No Product description Classification considered rationale 1. Preparation, in the form of a powder, consisting of 92 % sugar, 6 % 2106.90 GRIs 1 and 6 black currant powder, anticaking agent, citric acid and black currant flavouring, put up for retail sale in 32-gram sachets, intended to be consumed as a beverage after mixing with hot water. 2. Vanutide cridificar (INN List 100). 3002.20 3. Certain INN products. Chapters 28, 29 (See “INN List 101” at the end of this publication.) and 30 4. Certain INN products. Chapters 13, 29 (See “INN List 102” at the end of this publication.) and 30 5. Certain INN products. Chapters 28, 29, (See “INN List 103” at the end of this publication.) 30, 35 and 39 6. Re-classification of INN products.
    [Show full text]
  • Bempedoic Acid) Tablets, for Oral Use Most Common (Incidence ≥ 2% and Greater Than Placebo) Adverse Reactions Initial U.S
    HIGHLIGHTS OF PRESCRIBING INFORMATION • Tendon Rupture: Tendon rupture has occurred. Discontinue NEXLETOL These highlights do not include all the information needed to use at the first sign of tendon rupture. Avoid NEXLETOL in patients who NEXLETOL™ safely and effectively. See full prescribing information have a history of tendon disorders or tendon rupture. (5.2) for NEXLETOL. --------------------------------ADVERSE REACTIONS----------------------------­ NEXLETOL (bempedoic acid) tablets, for oral use Most common (incidence ≥ 2% and greater than placebo) adverse reactions Initial U.S. Approval: 2020 are upper respiratory tract infection, muscle spasms, hyperuricemia, back pain, abdominal pain or discomfort, bronchitis, pain in extremity, anemia, ----------------------------INDICATIONS AND USAGE--------------------------­ and elevated liver enzymes. (6.1) NEXLETOL is an adenosine triphosphate-citrate lyase (ACL) inhibitor indicated as an adjunct to diet and maximally tolerated statin therapy for the To report SUSPECTED ADVERSE REACTIONS, contact Esperion at treatment of adults with heterozygous familial hypercholesterolemia or 833-377-7633 (833 ESPRMED) or FDA at 1-800-FDA-1088 or established atherosclerotic cardiovascular disease who require additional www.fda.gov/medwatch. lowering of LDL-C. (1) --------------------------------DRUG INTERACTIONS----------------------------­ Limitations of Use: The effect of NEXLETOL on cardiovascular morbidity • Simvastatin: Avoid concomitant use of NEXLETOL with simvastatin and mortality has not been
    [Show full text]
  • CP.PMN.237 Bempedoic Acid (Nexletol)
    Clinical Policy: Bempedoic Acid (Nexletol), Bempedoic Acid/Ezetimibe (Nexlizet) Reference Number: CP.PMN.237 Effective Date: 09.01.20 Last Review Date: 02.21 Revision Log Line of Business: Commercial, HIM, Medicaid See Important Reminder at the end of this policy for important regulatory and legal information. Description The following are adenosine triphosphate-citrate lyase (ACL) inhibitors requiring prior authorization: bempedoic acid (Nexletol™) and bempedoic acid/ezetimibe (Nexlizet™). Nexlizet contains ezetimibe, which is a cholesterol absorption inhibitor. FDA Approved Indication(s) Nexletol and Nexlizet are indicated for use as adjuncts to diet and maximally tolerated statin therapy for the treatment of adults with heterozygous familial hypercholesterolemia (HeFH) or established atherosclerotic cardiovascular disease (ASCVD) who require additional lowering of low-density lipoprotein cholesterol (LDL-C). Limitation(s) of use: The effect of Nexletol and Nexlizet on cardiovascular morbidity and mortality has not been determined. Policy/Criteria Provider must submit documentation (such as office chart notes, lab results or other clinical information) supporting that member has met all approval criteria. It is the policy of health plans affiliated with Centene Corporation® that Nexletol and Nexlizet are medically necessary when the following criteria are met: I. Initial Approval Criteria A. Heterozygous Familial Hypercholesterolemia and Atherosclerotic Cardiovascular Disease (must meet all): 1. Diagnosis of one of the following (a or b): a. ASCVD as evidenced by a history of any one of the following conditions (i-vii): i. Acute coronary syndromes; ii. Clinically significant coronary heart disease (CHD) diagnosed by invasive or noninvasive testing (such as coronary angiography, stress test using treadmill, stress echocardiography, or nuclear imaging); iii.
    [Show full text]
  • Bempedoic Acid
    Drug and Biologic Coverage Policy Effective Date ............................................. 7/15/2020 Next Review Date ......................................... 7/1/2021 Coverage Policy Number .................................. 2015 Bempedoic acid Table of Contents Related Coverage Resources Coverage Policy ................................................... 1 Genetic Testing of Heritable Disorders FDA Approved Indications ................................... 4 Recommended Dosing ........................................ 4 General Background ............................................ 4 Coding/Billing Information .................................... 7 References .......................................................... 7 INSTRUCTIONS FOR USE The following Coverage Policy applies to health benefit plans administered by Cigna Companies. Certain Cigna Companies and/or lines of business only provide utilization review services to clients and do not make coverage determinations. References to standard benefit plan language and coverage determinations do not apply to those clients. Coverage Policies are intended to provide guidance in interpreting certain standard benefit plans administered by Cigna Companies. Please note, the terms of a customer’s particular benefit plan document [Group Service Agreement, Evidence of Coverage, Certificate of Coverage, Summary Plan Description (SPD) or similar plan document] may differ significantly from the standard benefit plans upon which these Coverage Policies are based. For example, a customer’s benefit
    [Show full text]
  • Bempedoic Acid, Bempedoic Acid/Ezetimibe (Nexletol™, Nexlizet™) EOCCO POLICY Policy Type: PA/SP Pharmacy Coverage Policy: EOCCO182
    bempedoic acid, bempedoic acid/ezetimibe (Nexletol™, Nexlizet™) EOCCO POLICY Policy Type: PA/SP Pharmacy Coverage Policy: EOCCO182 Description Bempedoic acid, bempedoic acid/ezetimibe (Nexletol, Nexlizet) is an orally administered adenosine triphosphate-citrate lyase inhibitor, and ezetimibe is an intestinal cholesterol absorption inhibitor . Length of Authorization Initial: six months Renewal: 12 months Quantity Limits Product Name Dosage Form Indication Quantity Limit As an adjunct to diet and bempedoic acid maximally tolerated statin 180 mg tablets 30 tablets/30 days (Nexletol) therapy for the treatment of adults with heterozygous familial hypercholesterolemia or bempedoic established atherosclerotic 180 mg/10 mg tablets acid/ezetimibe cardiovascular disease who 30 tablets/30 days (Nexlizet) require additional lowering of LDL-C Initial Evaluation I. Bempedoic acid, bempedoic acid/ezetimibe (Nexletol, Nexlizet) may be considered medically necessary when the following criteria below are met: A. Member is 18 years of age or older; AND B. Therapy is prescribed by, or in consultation with, a provider specializing in lipid management (e.g. cardiology, lipidology, endocrinology); AND C. Therapy with a maximally tolerated statin for at least an 8-week duration has been ineffective; AND 1. The member continues to have an LDL-cholesterol level greater than or equal to 70 mg/dL while on maximally tolerated statin therapy; AND 2. The member will continue maximally tolerated statin therapy in combination with bempedoic acid, bempedoic acid/ezetimibe (Nexletol, Nexlizet); AND 1 bempedoic acid, bempedoic acid/ezetimibe (Nexletol™, Nexlizet™) EOCCO POLICY 3. The member will not use bempedoic acid, bempedoic acid/ezetimibe (Nexletol, Nexlizet) in combination with simvastatin (Zocor) >20 mg or pravastatin (Pravachol) >40 mg; OR i.
    [Show full text]
  • Lääkeaineiden Yleisnimet (INN-Nimet) 21.6.2021
    Lääkealan turvallisuus- ja kehittämiskeskus Säkerhets- och utvecklingscentret för läkemedelsområdet Finnish Medicines Agency Lääkeaineiden yleisnimet (INN-nimet) 21.6.
    [Show full text]
  • Bempedoic Acid
    Esperion Announces Three Data Presentations of the NEXLETOL™ (bempedoic acid) Tablet and the NEXLIZET™ (bempedoic acid and ezetimibe) Tablet at the American College of Cardiology’s 69th Annual Scientific Session Together with World Congress of Cardiology March 28, 2020 ANN ARBOR, Mich., March 28, 2020 (GLOBE NEWSWIRE) -- Esperion (NASDAQ:ESPR) today announced that two pooled analyses from four Phase 3 clinical trials of NEXLETOL and results from the Phase 2 (1002-058) study of NEXLIZET were presented at the American College of Cardiology’s 69 th Scientific Session Together with World Congress of Cardiology (ACC.20/WCC). A poster titled “Bempedoic Acid 180 mg + Ezetimibe 10 mg Fixed Combination Drug Product vs Ezetimibe Alone or Placebo in Patients with Type 2 Diabetes and Hypercholesterolemia” was presented by Harold E Bays, MD, FOMA, FTOS, FACC, FACE, FNLA. The poster highlighted that in the Phase 2 (1002-058) study, NEXLIZET significantly lowered LDL-Cholesterol (LDL-C) by a mean 40% compared to placebo, reduced high-sensitivity C-reactive protein (hsCRP) by 25% compared to baseline and resulted in no worsening of glycemic control. The incidence of adverse events rates were generally comparable to placebo. In addition, a poster, titled “Factors Influencing Bempedoic Acid–Mediated Reductions in High-sensitivity C-reactive Protein: Analysis of Pooled Patient-level Data from 4 Phase 3 Clinical Trials” was presented by Eric S. G. Stroes, MD, PhD. The poster highlighted that in the pooled Phase 3 studies, NEXLETOL significantly lowered hsCRP in patients with hypercholesterolemia regardless of the presence or intensity of background statin therapy. In patients whose hsCRP levels were >2 mg/L at baseline, the analysis showed NEXLETOL significantly reduced this marker of inflammation by 42% at 12 weeks.
    [Show full text]
  • Anatomical Classification Guidelines V2021 EPHMRA ANATOMICAL CLASSIFICATION GUIDELINES 2021
    EPHMRA ANATOMICAL CLASSIFICATION GUIDELINES 2021 Anatomical Classification Guidelines V2021 "The Anatomical Classification of Pharmaceutical Products has been developed and maintained by the European Pharmaceutical Marketing Research Association (EphMRA) and is therefore the intellectual property of this Association. EphMRA's Classification Committee prepares the guidelines for this classification system and takes care for new entries, changes and improvements in consultation with the product's manufacturer. The contents of the Anatomical Classification of Pharmaceutical Products remain the copyright to EphMRA. Permission for use need not be sought and no fee is required. We would appreciate, however, the acknowledgement of EphMRA Copyright in publications etc. Users of this classification system should keep in mind that Pharmaceutical markets can be segmented according to numerous criteria." © EphMRA 2021 Anatomical Classification Guidelines V2021 CONTENTS PAGE INTRODUCTION A ALIMENTARY TRACT AND METABOLISM 1 B BLOOD AND BLOOD FORMING ORGANS 28 C CARDIOVASCULAR SYSTEM 36 D DERMATOLOGICALS 51 G GENITO-URINARY SYSTEM AND SEX HORMONES 58 H SYSTEMIC HORMONAL PREPARATIONS (EXCLUDING SEX HORMONES) 68 J GENERAL ANTI-INFECTIVES SYSTEMIC 72 K HOSPITAL SOLUTIONS 88 L ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS 96 M MUSCULO-SKELETAL SYSTEM 106 N NERVOUS SYSTEM 111 P PARASITOLOGY 122 R RESPIRATORY SYSTEM 124 S SENSORY ORGANS 136 T DIAGNOSTIC AGENTS 143 V VARIOUS 145 Anatomical Classification Guidelines V2021 INTRODUCTION The Anatomical Classification was initiated in 1971 by EphMRA. It has been developed jointly by Intellus/PBIRG and EphMRA. It is a subjective method of grouping certain pharmaceutical products and does not represent any particular market, as would be the case with any other classification system.
    [Show full text]
  • Efficacy and Safety of Triplet Therapy With
    Interactive! Click on any of Efficacy and Safety of Triplet Therapy With Bempedoic Acid, Ezetimibe, TAP TO RETURN these bubbles to TO KIOSK MENU jump to each and Atorvastatin in Patients With Hypercholesterolemia section Diane E. MacDougall, MS1; John Rubino, MD2; Lulu Ren Sterling, PhD1; Jeffrey C. Hanselman, MS1; Stephen J. Nicholls, MD, PhD3 Results & Methods 1Esperion Therapeutics Inc., Ann Arbor, MI; 2PMG Research of Raleigh, Raleigh, NC; Results 3Monash Cardiovascular Research Centre, Monash University, Melbourne, VIC, Australia Conclusions INTRODUCTION METHODS • Patients with hypercholesterolemia often fail to achieve sufficient cholesterol lowering, despite the use of guideline- recommended lipid-lowering therapies1-3 STUDY DESIGN AND TREATMENT • Bempedoic acid is an oral, first-in-class ATP-citrate lyase inhibitor in development for treating hypercholesterolemia4,5 • Phase 2, randomized, double-blind, placebo-controlled study – The active form of bempedoic acid (bempedoyl-CoA) inhibits ATP-citrate lyase, an enzyme upstream of • The study consisted of 2 phases (Figure 1): HMG-CoA reductase (the target of statins) in the cholesterol biosynthesis pathway – A 6-week screening/washout period during which patients – Bempedoic acid is a prodrug that is activated in the liver by very long-chain acyl-CoA synthetase 1 (ACSVL1) discontinued lipid-lowering drugs and nutritional supplements – A double-blind treatment period in which patients were – ACSVL1 expression is limited to the liver; therefore, bempedoic acid is not converted to bempedoyl-CoA in randomized 2:1 to treatment with triplet therapy (bempedoic acid skeletal muscle 180 mg + ezetimibe 10 mg + atorvastatin 20 mg) or placebo once • In phase 3 clinical trials, bempedoic acid significantly lowered low-density lipoprotein cholesterol (LDL-C) when daily for 6 weeks administered alone or as an add-on to background lipid-lowering therapy6-9 OBJECTIVE FIGURE 1.
    [Show full text]
  • A Review of the Efficacy and Tolerability of Bempedoic Acid In
    American Journal of Cardiovascular Drugs https://doi.org/10.1007/s40256-020-00399-w REVIEW ARTICLE A Review of the Efcacy and Tolerability of Bempedoic Acid in the Treatment of Hypercholesterolemia Stephanie Niman1 · Khyatiben Rana1 · Jessica Reid1,2 · Mae Sheikh‑Ali3 · Todd Lewis4 · Rushab R. Choksi1 · Rebecca F. Goldfaden1 © Springer Nature Switzerland AG 2020 Abstract Despite the widespread use of statins and ezetimibe to decrease low-density lipoprotein cholesterol (LDL-C) levels and associated atherosclerotic cardiovascular disease (ASCVD), many patients do not achieve adequate LDL-C lowering as per the recommended American College of Cardiology (ACC)/American Heart Association (AHA) and European Society of Cardiology (ESC)/European Atherosclerosis Society (EAS) guidelines and demonstrate residual cardiovascular risk. The introduction of proprotein convertase subtilisin/kexin type 9 (PCSK-9) inhibitors in 2015 was a promising addition to hypercholesterolemia therapies, but their cost and subcutaneous administration has limited their use, and therefore, new afordable and patient friendly treatment strategies are crucial to help reduce ASCVD risk. Bempedoic acid, a drug currently under investigation, is a small molecule that has been shown to upregulate LDL receptors, decrease LDL-C, and reduce atherosclerotic plaque formation in hypercholesterolemic patients. Furthermore, bempedoic acid is a prodrug that becomes activated by an enzyme expressed primarily in the liver, allowing it to avoid the potential myotoxicity associated with statin
    [Show full text]