DOCSLIB.ORG

Bococizumab for Primary Hyperlipidaemia and Mixed Dyslipidaemia – Adjunctive to Statin Therapy And/Or Diet

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Bococizumab for Primary Hyperlipidaemia and Mixed Dyslipidaemia – Adjunctive to Statin Therapy And/Or Diet October Horizon Scanning Research & 2016 Intelligence Centre Bococizumab for primary hyperlipidaemia and mixed dyslipidaemia – adjunctive to statin therapy and/or diet NIHR HSRIC ID: 6837 Lay summary Bococizumab is a new drug to treat high levels of fat and cholesterol in the bloodstream (primary hyperlipidemia and mixed dyslipidemia). These conditions can cause a build-up of fatty deposits (plaques) in the arteries, which may lead to heart attacks and strokes. Bococizumab is given by subcutaneous injection. Some studies have suggested that this drug in combination with other cholesterol lowering drugs may help to reduce the risk of heart attacks and strokes. This briefing is based on information available at the time of research and a limited literature search. It is not intended to be a definitive statement on the safety, efficacy or effectiveness of the health technology covered and should not be used for commercial purposes or commissioning without additional information. This briefing presents independent research funded by the National Institute for Health Research (NIHR). The views expressed are those of the author and not necessarily those of the NHS, the NIHR or the Department of Health. Horizon Scanning Research & Intelligence Centre University of Birmingham [email protected] www.hsric.nihr.ac.uk @OfficialNHSC TARGET GROUPS • Primary hyperlipidaemia: heterozygous familial and non-familial – adjunctive to diet; in combination with statin. • Mixed dyslipidaemia – adjunctive to diet; in combination with statin. • Primary hyperlipidaemia or mixed dyslipidaemia: statin-intolerant, or patients in whom statins are contraindicated – adjunctive to diet. TECHNOLOGY DESCRIPTION Bococizumab (PF-04950615; RN316) is one of a new class of lipid regulating drugs, the proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors. Unlike others in its class, which are fully human (e.g. evolocumab and alirocumab), bococizumab is a humanised IgG2Δa monoclonal antibody (mAb) that targets this serine protease. The accumulation of low-density lipoprotein-cholesterol (LDL-C) in the blood can result in atherosclerosis, which may lead to cardiovascular disease (CVD), e.g. coronary heart disease (CHD) or stroke1. The low-density lipoprotein (LDL) receptor binds LDL-cholesterol to mediate its clearance from the circulation. Recent studies suggest that gain-of-function mutations in PCSK9 increase LDL-C levels, and thus the risk of cardiovascular events; conversely, genetic variations linked to reduced PCSK9 function decrease plasma LDL-C, subsequently lowering risk2,3. The PCSK9 protein interferes with the clearance of LDL-C by binding to, and inducing the degradation of the LDL receptor2. Bococizumab inhibits the PCSK9 protein, preventing PCSK9-mediated degradation2. Bococizumab is intended to treat primary hyperlipidaemia (heterozygous familial and non-familial) and mixed dyslipidaemia as an adjunctive to diet and statins, or primary hyperlipidaemia or mixed dyslipidaemia as a monotherapy in those who are statin-intolerant, or for whom statins are contraindicated. Bococizumab is administered by subcutaneous (SC) auto-injector device at 150mg given once every two weeks in combination with statins and/or diet on a continuing basis. It is not currently licensed in the EU for any other indication. INNOVATION and/or ADVANTAGES PCSK9 inhibitors, like bococizumab, are intended to prevent cardiovascular events. While statin therapy considerably reduces the risk of CVD, cardiovascular morbidity and mortality still occur in a significant portion of subjects receiving this therapy, in particular those with familial hypercholesterolemia (FH) – characterised by extremely high levels of LDL-C4,5. If licensed, bococizumab has the potential to reduce residual cardiovascular (CV) risk in those with primary hyperlipidaemia and mixed dyslipidaemia; or reduce CV risk in those who are statin-intolerant, or for whom a statin is contraindicated, a group with few well-tolerated effective therapies available. DEVELOPER Pfizer Limited. Horizon Scanning Research & Intelligence Centre AVAILABILITY, LAUNCH OR MARKETING In phase III clinical trials. PATIENT GROUP BACKGROUND Dyslipidaemia encompasses a number of conditions in which disturbances in fat metabolism lead to changes in lipid concentrations in the blood. These include hypercholesterolaemia, hyperlipidaemia and mixed dyslipidaemia. Hypercholesterolaemia is defined as raised levels of cholesterol in the blood, typically including elevated LDL-C. Hyperlipidaemia refers to raised cholesterol and/or raised triglycerides (TG) – hypercholesterolaemia and/or hypertriglyceridaemia. Mixed dyslipidaemia is defined as hyperlipidaemia with elevations in LDL-C and TG accompanied by decreased levels of high-density lipoprotein cholesterol (HDL-C)6. Primary dyslipidaemia may be caused by a mixture of environmental factors and genetic predisposition; these include homozygous or heterozygous mutations in the LDL cholesterol receptor gene (a cause of FH) and lipoprotein lipase gene (a cause of familial hypertriglyceridaemia), or more commonly, by the interaction of several genes with dietary and other factors such as smoking or physical inactivity (non-familial dyslipidaemia)6. Most people with hypercholesterolaemia have cholesterol concentrations that are only mildly or moderately elevated, and show no clinical symptoms. However, severe hypercholesterolaemia can cause xanthomas (lesions on the skin containing cholesterol and fats), arcus corneae (cholesterol deposits in the eyes), and significantly increased risk of atherosclerosis and therefore CVD6. The risk of CVD is directly related to blood cholesterol levels and it is estimated that more than 50% of CVD in developed countries is a result of blood cholesterol levels higher than 3.8mmol/litre (68.5mg/dL)7. People with FH have marked elevations in cholesterol and are at particular risk of developing premature CVD6. CLINICAL NEED and BURDEN OF DISEASE It is estimated that 6 in 10 adults in England have cholesterol levels above 5.0mmol/litre (193mg/dL), a leading risk factor for CVD8. In England, there were 383,640 admissions for the four main types of CVD (ICD10: CHD I20–I25; stroke I61–I64; peripheral arterial disease I73.9; and aortic disease I71) in 2014-159. CHD is the leading cause of death in the UK, responsible for more than 73,000 deaths each year. About 1 in 6 men and 1 in 10 women die from CHD. In 2012-2013, there were around 2.3 million people living with CHD (around 1.3 million people affected by angina, the most common symptom of CHD), 1.2 million people recovering from a stroke, around 1.1 million living with atrial fibrillation, and just over 480,000 with heart failure in the UK8,10. Primary non-familial hypercholesterolaemia affects about 4% of the adult population, totalling approximately 1.5 million people in England, of whom an estimated 600,000 are diagnosed and 460,000 are receiving treatment. Primary heterozygous FH affects an estimated 1 in 500 people, totalling 106,000 in England (although only 15–17% are diagnosed)6. In June 2016 alone, 5,541,338 items of lipid-regulating drugs were dispensed in England at a net ingredient cost of around £17.1 million11. It has been estimated that 12,088 people with non-familial hypercholesterolaemia and 1,749 with FH will have LDL-C levels that are not adequately controlled by their current lipid- 3 Horizon Scanning Research & Intelligence Centre regulating treatment12. However, the proportion of those with severe hypertriglyceridaemia that is not adequately controlled by current lipid-regulating drugs is not known. PATIENT PATHWAY RELEVANT GUIDANCE NICE Guidance • NICE technology appraisal. Evolocumab for treating primary hypercholesterolaemia and mixed dyslipidaemia (TA394). June 201613. • NICE technology appraisal. Alirocumab for treating primary hypercholesterolaemia and mixed dyslipidaemia (TA393). June 201614. • NICE technology appraisal. Ezetimibe for treating primary heterozygous-familial and non-familial hypercholesterolaemia (TA385). February 201615. • NICE clinical guidelines. Cardiovascular disease: risk assessment and reduction, including lipid modification (CG181). July 20147. • NICE clinical guidelines. Identification and management of familial hypercholesterolaemia. (CG71). August 200816. • NICE quality standard. Cardiovascular risk assessment and lipid modification (QS100). September 201517. • NICE quality standard. Familial hypercholesterolaemia (QS41). August 201318. NHS England Policies and Guidance • NHS England. 2013/14 NHS Standard Contract for Severe and Complex Obesity (All Ages). A05/S/a. • NHS England. 2013/14 NHS Standard Contract for Insulin-Resistant Diabetes Services (All Ages). A03/S(HSS)/b. • NHS England. 2013/14 NHS Standard Contract Paediatric Medicine: Endocrinology and Diabetes. E03/S/e. • NHS England. Clinical Commissioning Policy: Complex and Specialised Obesity Surgery. NHS ENGLAND/A05/P/a. April 2013. Other Guidance • European Society of Cardiology. European guidelines on cardiovascular disease prevention in clinical practice. 201619. • American College of Cardiology. 2016 ACC expert consensus decision pathway on the role of non-statin therapies for LDL-cholesterol lowering in the management of atherosclerotic cardiovascular disease risk. 201620. • American College of Cardiology. ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular disease risk: a new paradigm supported by more evidence. 201321. • European Society
Load more

Recommended publications
  • 125559Orig1s000
    CENTER FOR DRUG EVALUATION AND RESEARCH APPLICATION NUMBER: 125559Orig1s000 PHARMACOLOGY REVIEW(S) Tertiary Pharmacology/Toxicology Review Date: July 14, 2015 From: Timothy J. McGovern, Ph.D., ODE Associate Director for Pharmacology and Toxicology, OND IO BLA: 125559 Agency receipt date: November 24, 2014 Drug: PRALUENT (alirocumab) Sponsor: Sanofi-Aventis U.S. LLC Indication: Adult patients with primary hypercholesterolemia (non-familial and heterozygous familial) or mixed dyslipidemia Reviewing Division: Division of Metabolism and Endocrinology Products Introductory Comments: The pharmacology/toxicology reviewer and supervisor concluded that the nonclinical data support approval of PRALUENT (alirocumab) for the indication listed above. Alirocumab is a human IgG1 monoclonal antibody that binds to human PCSK9 (Proprotein Convertase Subtilisin Kexin Type 9). The recommended Established Pharmacologic Class for alirocumab is PCSK9 inhibitor antibody. There are no approved products in this class currently. An appropriate nonclinical program was conducted by the sponsor to support approval of alirocumab. Alirocumab elicited expected pharmacological responses in rats, hamsters, and monkeys; alirocumab lowered total cholesterol and LDL-cholesterol in the species tested and decreased HDL-cholesterol in rats and hamsters. The primary nonclinical toxicity studies of alirocumab were conducted in rats and monkeys for up to 6 months duration with weekly subcutaneous and intravenous dosing. No significant adverse findings were observed at the doses tested which achieved exposure multiples up to 11-fold in rats and 103-fold in monkeys compared to the maximum recommended human dose of 150 mg alirocumab administered subcutaneously once every two weeks. Findings in the liver and adrenal glands of rats were associated with exaggerated pharmacologic effects.
    [Show full text]
  • Lipid-Lowering Therapy and Low-Density Lipoprotein Cholesterol
    Kristensen et al. BMC Cardiovascular Disorders (2020) 20:336 https://doi.org/10.1186/s12872-020-01616-9 RESEARCH ARTICLE Open Access Lipid-lowering therapy and low-density lipoprotein cholesterol goal attainment after acute coronary syndrome: a Danish population-based cohort study Marie Skov Kristensen1, Anders Green2,3, Mads Nybo4, Simone Møller Hede2, Kristian Handberg Mikkelsen5, Gunnar Gislason1,6,7,8, Mogens Lytken Larsen9 and Annette Kjær Ersbøll1* Abstract Background: Patients with acute coronary syndrome (ACS) are at high risk of recurrent cardiovascular (CV) event. The European guidelines recommend low-density lipoprotein cholesterol (LDL-C) levels < 1.8 mmol/L and early initiation of intensive lipid-lowering therapy (LLT) to reduce CV risk. In order to reduce the risk of further cardiac events, the study aimed to evaluate LDL-C goal attainment and LLT intensity in an incident ACS population. Methods: A cohort study of patients with residency at Funen in Denmark at a first-ever ACS event registered within the period 2010–2015. Information on LLT use and LDL-C levels was extracted from national population registers and a Laboratory database at Odense University Hospital. Treatments and lipid patterns were evaluated during index hospitalization, at 6-month and 12-month follow-up. Results: Among 3040 patients with an LDL-C measurement during index hospitalization, 40.7 and 39.0% attained the recommended LDL-C target value (< 1.8 mmol/L) within 6- and 12-month follow-up, respectively. During 6- and 12-month follow-up, a total of 89.2% (20.2%) and 88.4% (29.7%) used LLT (intensive LLT).
    [Show full text]
  • Us 2018 / 0296525 A1
    UN US 20180296525A1 ( 19) United States (12 ) Patent Application Publication (10 ) Pub. No. : US 2018/ 0296525 A1 ROIZMAN et al. ( 43 ) Pub . Date: Oct. 18 , 2018 ( 54 ) TREATMENT OF AGE - RELATED MACULAR A61K 38 /1709 ( 2013 .01 ) ; A61K 38 / 1866 DEGENERATION AND OTHER EYE (2013 . 01 ) ; A61K 31/ 40 ( 2013 .01 ) DISEASES WITH ONE OR MORE THERAPEUTIC AGENTS (71 ) Applicant: MacRegen , Inc ., San Jose , CA (US ) (57 ) ABSTRACT ( 72 ) Inventors : Keith ROIZMAN , San Jose , CA (US ) ; The present disclosure provides therapeutic agents for the Martin RUDOLF , Luebeck (DE ) treatment of age - related macular degeneration ( AMD ) and other eye disorders. One or more therapeutic agents can be (21 ) Appl. No .: 15 /910 , 992 used to treat any stages ( including the early , intermediate ( 22 ) Filed : Mar. 2 , 2018 and advance stages ) of AMD , and any phenotypes of AMD , including geographic atrophy ( including non -central GA and Related U . S . Application Data central GA ) and neovascularization ( including types 1 , 2 and 3 NV ) . In certain embodiments , an anti - dyslipidemic agent ( 60 ) Provisional application No . 62/ 467 ,073 , filed on Mar . ( e . g . , an apolipoprotein mimetic and / or a statin ) is used 3 , 2017 . alone to treat or slow the progression of atrophic AMD Publication Classification ( including early AMD and intermediate AMD ) , and / or to (51 ) Int. CI. prevent or delay the onset of AMD , advanced AMD and /or A61K 31/ 366 ( 2006 . 01 ) neovascular AMD . In further embodiments , two or more A61P 27 /02 ( 2006 .01 ) therapeutic agents ( e . g ., any combinations of an anti - dys A61K 9 / 00 ( 2006 . 01 ) lipidemic agent, an antioxidant, an anti- inflammatory agent, A61K 31 / 40 ( 2006 .01 ) a complement inhibitor, a neuroprotector and an anti - angio A61K 45 / 06 ( 2006 .01 ) genic agent ) that target multiple underlying factors of AMD A61K 38 / 17 ( 2006 .01 ) ( e .
    [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]
  • PCSK9 Inhibitors – Clinical Applications
    VOLUME 39 : NUMBER 5 : OCTOBER 2016 EXPERIMENTAL AND CLINICAL PHARMACOLOGY PCSK9 inhibitors – clinical applications Robert Schmidli Consultant endocrinologist SUMMARY Department of Endocrinology The enzyme PCSK9 has an important role in regulating low-density lipoprotein (LDL) receptors Canberra Hospital and concentrations of LDL cholesterol. Inhibiting this enzyme could therefore reduce the incidence of ischaemic heart disease. Keywords The monoclonal antibodies alirocumab, evolocumab and bococizumab are directed against alirocumab, bococizumab, PCSK9 and inhibit its activity. Phase II trials have shown alirocumab and evolocumab to be evolocumab, ischaemic heart disease, LDL effective at lowering LDL cholesterol. cholesterol, proprotein Preliminary results of these phase II trials show potential benefits in ischaemic heart disease. convertase subtilisin/kexin type 9 Reports of adverse effects, including muscular symptoms and neurocognitive changes, were low. Large phase III cardiovascular outcome trials of these monoclonal antibodies will determine their Aust Prescr 2016;39:168–70 safety and efficacy. These drugs may have a role in the management of patients at very high risk http://dx.doi.org/10.18773/ of cardiovascular events such as those with familial hypercholesterolaemia. austprescr.2016.061 Introduction PCSK9 inhibitory antibodies The incidence of deaths from ischaemic heart disease Studies of uncommon mutations, such in Australia has reduced since the 1960s. While about as the LDL‑receptor mutations in familial half of this reduction is due to interventions such as hypercholesterolaemia, have led to important coronary revascularisation and secondary prevention, therapeutic advances in the study of lipids and the remainder is due to addressing risk factors such as cardiovascular disease. Proprotein convertase smoking, lipids and hypertension.
    [Show full text]
  • Background A. Rodríguez-Alarcón1, C. López1, E. González-Colominas1
    LONG-TERM EFFICACY, SAFETY AND ADHERENCE TO ALIROCUMAB IN PATIENTS WITH DYSLIPIDAEMIA FROM A TERTIARY HOSPITAL COHORT A. Rodríguez-Alarcón1, C. López1, E. González-Colominas1, S. Luque1, Ll. Recasens2, J. Pedro-Botet3, A. Oliveras4, R. González1, L. Tarrason1, S. Grau1 1Pharmacy Department. Parc de Salut Mar. Barcelona. 2Cardiology Department. Parc de Salut Mar. Barcelona. 3Endocrinology Department. Parc de Salut Mar. Barcelona. 4Nephrology Department. Parc de Salut Mar. Barcelona. Key words: Alirocumab, efficacy, safety, adherence Abstract number: 4CPS-023 ATC code: C10 - Lipid modifying agents Background Alirocumab is a monoclonal antibody approved for the treatment of hypercholesterolemia but long-term clinical data are still limited. Objectives To assess the long-term efficacy, safety and adherence to alirocumab after 96 weeks of treatment in a cohort of patients with dyslipidemia. Material and methods Retrospective observational study performed in a university tertiary hospital. All patients starting alirocumab before September 2017 in our institution and treated for at least 96 weeks were included. Data collected: demographic, clinical and alirocumab data, including treatment efficacy (% LDLc reduction from baseline to 96 weeks) and adherence (Medication Possession Ratio). Results Thirty-three patients started alirocumab treatment during 2017 being 31 (93.9%) still on treatment after 96 weeks. Two patients (6.1%) discontinued therapy: one due to an active malignancy and one due to loss of follow-up. Demographic LDLc reduction Adherence Men, % 58,1 Age (years), median (IQR) 65 (11) Alirocumab 75 mg/2 weeks, % 87,1 Alirocumab 150 mg/2 weeks, % 12,9 Secondary prevention, % 83,9 High cardiovascular risk, % 80,6 Efficacy: LDLc reduction (median (IQR)): 59.5 Median (range) adherence: 100% Type of hypercholesterolemia, %: (22.6%).
    [Show full text]
  • Intervention to Improve LDL Receptor Function Emerging Therapies
    Intervention to improve LDL receptor function Emerging Therapies Marina Cuchel, MD, PhD Perelman School of Medicine University of Pennsylvania Most Lipid Lowering Drugs Affect LDL-C Levels By Up-Regulating the LDLR B100 apoB MTP VLDL TG TG statins ezetimibe bile acid sequestrants IDL PCSK9 -inhibitors LDL TG Cuchel NLA 2017 Do we really need more LDL-C lowering drugs? • LDL-C still not a goal with existing LLTs in a significant portion of subjects • Drug intolerance (statins) • Cost of new treatments • Other reasons Cuchel NLA 2017 Outline • PCSK9 – beyond monoclonal antibodies • ETC-1002 – inhibiting upstream HMGCoAR • Replacing LDLR - Gene therapy • ANGPTL3 inhibitors and other drug affecting LDL production Cuchel NLA 2017 PCSK9 enhances LDLR degradation Cuchel NLA 2017 Use of PCSK9i is complementary to that of statins PCSK9i evolucumab alirocumab [other monoclonal ABs] statins HMG-CoA ↑LDLR ↑PCSK9 ↓LDL-C ↓Cholesterol Cuchel NLA 2017 PCSK9 inhibition is very effective in lowering LDL-C Sabatine MS et al. N Engl J Med 2017. DOI: 10.1056/NEJMoa1615664 Cuchel NLA 2017 PCSK9 – beyond monoclonal Antibodies • Monoclonal PCSK9i are expensive • Require high doses • Are injectable • ?May lose responsiveness over time? Cuchel NLA 2017 Targeting PCSK9 with novel strategies • Vaccines • siRNA • Small molecules Cuchel NLA 2017 Targeting PCSK9 with novel strategies Vaccines antibodies response SREBP-2 pathway ↑ HMGCoA Red ↑ LDL-R Target protein ↑Epitope PCSK9 identification Conjugation with Administration Antibodies foreign peptide production Clinicaltrials.gov NCT02508896 Cuchel NLA 2017 Vaccine against PCSK9 lowers LDL-C in primates Crossey E. Vaccine, 2015 , 33, 5747–5755 Cuchel NLA 2017 Targeting PCSK9 with novel strategies siRNA SREBP-2 pathway ↑ HMGCoA Red ↑ LDL-R ↓PCSK9 Gene silencing Clinicaltrials.gov NCT02597127, NCT02314442 Cuchel NLA 2017 The RNAi inhibitor of PCSK9 - inclisiran - lowers PCSK9 and LDL-C levels in humans Ray KK et al.
    [Show full text]
  • A61p1/16 (2006.01) A61p3/00 (2006.01) Km, Ml, Mr, Ne, Sn, Td, Tg)
    ( (51) International Patent Classification: TR), OAPI (BF, BJ, CF, CG, Cl, CM, GA, GN, GQ, GW, A61P1/16 (2006.01) A61P3/00 (2006.01) KM, ML, MR, NE, SN, TD, TG). A61K 31/192 (2006.01) C07C 321/28 (2006.01) Declarations under Rule 4.17: (21) International Application Number: — as to the applicant's entitlement to claim the priority of the PCT/IB2020/000808 earlier application (Rule 4.17(iii)) (22) International Filing Date: Published: 25 September 2020 (25.09.2020) — with international search report (Art. 21(3)) (25) Filing Language: English — before the expiration of the time limit for amending the claims and to be republished in the event of receipt of (26) Publication Language: English amendments (Rule 48.2(h)) (30) Priority Data: 62/906,288 26 September 2019 (26.09.2019) US (71) Applicant: ABIONYX PHARMA SA [FR/FR] ; 33-43 Av¬ enue Georges Pompidou, Batiment D, 31130 Bahna (FR). (72) Inventor: DASSEUX, Jean-Louis, Henri; 7 Allees Charles Malpel, Bat. B, 31300 Toulouse (FR). (74) Agent: HOFFMANN EITLE PATENT- UND RECHTSANWALTE PARTMBB, ASSOCIATION NO. 151; Arabellastrasse 30, 81925 Munich (DE). (81) Designated States (unless otherwise indicated, for every kind of national protection available) : AE, AG, AL, AM, AO, AT, AU, AZ, BA, BB, BG, BH, BN, BR, BW, BY, BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DJ, DK, DM, DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, HR, HU, ID, IL, IN, IR, IS, IT, JO, JP, KE, KG, KH, KN, KP, KR, KW, KZ, LA, LC, LK, LR, LS, LU, LY, MA, MD, ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, PA, PE, PG, PH, PL, PT, QA, RO, RS, RU, RW, SA, SC, SD, SE, SG, SK, SL, ST, SV, SY, TH, TJ, TM, TN, TR, TT, TZ, UA, UG, US, UZ, VC, VN, WS, ZA, ZM, ZW.
    [Show full text]
  • PCSK9 Inhibitor Non-Response in a Patient with Preserved LDL Receptor
    PCSK9 inhibitor non-response in a patient with preserved LDL receptor function: A case study Losh C, Underberg J Murray Hill Medical Group and New York University School of Medicine, New York, NY Background Results Conclusions PCSK9 inhibitors (PCSK9Is) are monoclonal LDL-C levels after three and seven weeks Absence of LDL receptor activity is not the antibodies that bind to serum PCSK9 and Response to Statin Therapy of therapy with alirocumab 75 mg were 235 only mechanism of PCSK9 inhibitor non- delay LDL receptor degradation. Two mg/dL and 239 mg/dL respectively. Three response. An alteration in the PCSK9 PCSK9Is are commercially available: and seven weeks after up-titration, LDL-C Intervention LDL-C (mg/dL) Change (%) evolocumab and alirocumab. FDA approved binding site for alirocumab and indications include LDL cholesterol (LDL-C) was 249 mg/dL and 292 mg/dL, evolocumab is proposed as a hypothetical lowering on maximally tolerated statin respectively. Total duration of alirocumab None 283 — mechanism for non-response in this therapy was 16 weeks. LDL-C was 253 therapy in patients with ASCVD and Familial patient. Other alternatives include Hypercholesterolemia (FH). Among patients mg/dL after 3 weeks of therapy with pitavastatin 2 mg 238 -15.9% immunogenicity, noncompliance, or faulty with LDL receptor mutations, those with evolocumab, at which time PCSK9 1 dose/week partial loss of function typically respond well inhibitor therapy was discontinued due to pitavastatin 2 mg injection techniqueReferences. 216 -23.7% to PCSK9 inhibition, while those with lack of clinical response. 2 doses/week Amgen Inc. (2015). Repatha: Highlights of homozygous receptor-negative mutations, pitavastatin 2 mg ie.
    [Show full text]
  • Praluent® (Alirocumab)
    Praluent® (alirocumab) – New orphan indication • On April 1, 2021, the FDA approved Regeneron’s Praluent (alirocumab), as an adjunct to other low density lipoprotein cholesterol (LDL-C)-lowering therapies in adult patients with homozygous familial hypercholesterolemia (HoFH) to reduce LDL-C. • Praluent is also approved: — To reduce the risk of myocardial infarction, stroke, and unstable angina requiring hospitalization in adults with established cardiovascular disease. — As an adjunct to diet, alone or in combination with other LDL-C-lowering therapies, in adults with primary hyperlipidemia, including heterozygous familial hypercholesterolemia (HeFH), to reduce LDL-C. • The approval of Praluent for the new indication was based on ODYSSEY HoFH, a double-blind, placebo-controlled study in 45 adult patients with HoFH. Patients were taking maximally tolerated doses of statins with or without other lipid-lowering therapy and required additional LDL-C reduction. Patients were randomized to Praluent or placebo. — At week 12, the treatment difference between Praluent and placebo in mean LDL-C percent change from baseline was -36% (95% CI: -51, -20; p < 0.0001). • The recommended dose of Praluent for the treatment of HoFH is 150 mg once every 2 weeks administered subcutaneously. — LDL-C should be assessed when clinically appropriate. The LDL-lowering effect of Praluent may be measured as early as 4 weeks after initiation. — Refer to the Praluent drug label for dosing for its other indications optumrx.com ® OptumRx specializes in the delivery, clinical management and affordability of prescription medications and consumer health products. ® We are an Optum company — a leading provider of integrated health services. Learn more at optum.com.
    [Show full text]
  • Praluent, INN-Alirocumab
    ANNEX I SUMMARY OF PRODUCT CHARACTERISTICS 1 1. NAME OF THE MEDICINAL PRODUCT Praluent 75 mg solution for injection in pre-filled pen Praluent 150 mg solution for injection in pre-filled pen Praluent 75 mg solution for injection in pre-filled syringe Praluent 150 mg solution for injection in pre-filled syringe Praluent 300 mg solution for injection in pre-filled pen 2. QUALITATIVE AND QUANTITATIVE COMPOSITION Praluent 75 mg solution for injection in pre-filled pen Each single-use pre-filled pen contains 75 mg alirocumab in 1 ml solution. Praluent 75 mg solution for injection in pre-filled syringe Each single-use pre-filled syringe contains 75 mg alirocumab in 1 ml solution. Praluent 150 mg solution for injection in pre-filled pen Each single-use pre-filled pen contains 150 mg alirocumab in 1 ml solution. Praluent 150 mg solution for injection in pre-filled syringe Each single-use pre-filled syringe contains 150 mg alirocumab in 1 ml solution. Praluent 300 mg solution for injection in pre-filled pen Each single-use pre-filled pen contains 300 mg alirocumab in 2 ml solution. Alirocumab is a human IgG1 monoclonal antibody produced in Chinese Hamster Ovary cells by recombinant DNA technology. For the full list of excipients, see section 6.1. 3. PHARMACEUTICAL FORM Solution for injection (injection) Clear, colourless to pale yellow solution. pH: 5.7 – 6.3 Osmolality: Praluent 75 mg solution for injection 293 - 439 mOsm/kg Praluent 150 mg solution for injection 383 - 434 mOsm/kg Praluent 300 mg solution for injection 383 – 434 mOsm/kg 2 4.
    [Show full text]
  • Pharmacogenomics Variability of Lipid-Lowering Therapies in Familial Hypercholesterolemia
    Journal of Personalized Medicine Review Pharmacogenomics Variability of Lipid-Lowering Therapies in Familial Hypercholesterolemia Nagham N. Hindi 1,†, Jamil Alenbawi 1,† and Georges Nemer 1,2,* 1 Division of Genomics and Translational Biomedicine, College of Health and Life Sciences, Hamad Bin Khalifa University, Doha P.O. Box 34110, Qatar; [email protected] (N.N.H.); [email protected] (J.A.) 2 Department of Biochemistry and Molecular Genetics, Faculty of Medicine, American University of Beirut, Beirut DTS-434, Lebanon * Correspondence: [email protected]; Tel.: +974-445-41330 † Those authors contributed equally to the work. Abstract: The exponential expansion of genomic data coupled with the lack of appropriate clinical categorization of the variants is posing a major challenge to conventional medications for many common and rare diseases. To narrow this gap and achieve the goals of personalized medicine, a collaborative effort should be made to characterize the genomic variants functionally and clinically with a massive global genomic sequencing of “healthy” subjects from several ethnicities. Familial- based clustered diseases with homogenous genetic backgrounds are amongst the most beneficial tools to help address this challenge. This review will discuss the diagnosis, management, and clinical monitoring of familial hypercholesterolemia patients from a wide angle to cover both the genetic mutations underlying the phenotype, and the pharmacogenomic traits unveiled by the conventional and novel therapeutic approaches. Achieving a drug-related interactive genomic map will potentially benefit populations at risk across the globe who suffer from dyslipidemia. Citation: Hindi, N.N.; Alenbawi, J.; Nemer, G. Pharmacogenomics Variability of Lipid-Lowering Keywords: familial hypercholesterolemia; pharmacogenomics; PCSK9 inhibitors; statins; ezetimibe; Therapies in Familial novel lipid-lowering therapy Hypercholesterolemia.
    [Show full text]