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Microsoft word - vamv045_toc_150129

****Published February 2015***
MarketVIEW: Cholesterol (PCSK9) vaccines (CAT: VAMV045)

Product Name
MarketVIEW: Cholesterol (PCSK9) vaccines
Description
Global vaccine commercial opportunity assessment Contents
Executive presentation + 1 forecast model Therapeutic Area
Publication date
Catalogue No
Cardiovascular disease(s) (CVD) are prominent within the 10 leading causes of death in high-income countries. The most common manifestations of CVD are coronary heart disease (CHD), ischaemic stroke, and peripheral arterial disease (PAD). Raised low-density lipoprotein cholesterol (LDL-C), smoking, and uncontrolled hypertension are major risk factors the development of CVD. By 2030 almost 24.3M people/year globally are predicted to die from CVD. Currently Statins (HMG-CoA reductase inhibitors) are the most effective drug class for reducing LDL-C but differ in their LDL-C lowering capacity. In addition, several novel therapies are in development to reduce LDL-C levels in patients with severe hypercholesterolemia. These include PCSK9 inhibitors (monoclonals) of which Sanofi's SAR236553 (REGN727) PRALUENTTM
and Amgen's evolocumab RAPATHATM have now been filed for registration in both the US and EU. Both monoclonals were
shown to reduce LDL-C levels by 40 to 60% in combination with statins/ezetimibe in high-risk patients and those with homozygous familial hypercholesterolaemia. CVD outcomes studies are now ongoing. Some companies (Pfizer and AFFiRiS AG) are also investigating the possibility of preclinical PCSK9 vaccines that could help reduce LDL-C levels in high-risk patients who cannot achieve guideline LDL-C treatment goals. Vaccines could have the added benefit of lower cost and less frequency of administration than monoclonals. This MarketVIEW product contains a comprehensive MS Excel-based model + summary presentation which forecasts the
potential commercial value of PCSK9 (cholesterol) vaccines + monoclonals across major Western1 markets until 2030. The model contains value ($ m) and volume (mio doses) predictions per product type along with timeframe, pricing and penetration estimates for all target populations. The product also includes an in depth review of latest epidemiological trends, lipid lowering treatments/guidelines and latest developments in R&D. 1 SECONDARY PREVENTION - US, Canada, Australia, UK, France, Italy, Germany, Spain, Other Europe and Australia

VacZine Analytics has closely monitored all significant source material pertaining to PCSK9 inhibitors, coronary heart disease
(CHD), ischaemic stroke, and peripheral arterial disease (PAD) and other target groups. Source materials used are literature articles, government websites, medical bodies and associations, conference proceedings etc. Previously published research by VacZine Analytics in the field of novel vaccines has also been utilised.
PRODUCT CONTENTS:
Published February 2015 (CAT No: VAMV045)
****This product is composed of two forecast models and a summary presentation Author's note Contents Executive Summary Commercial model: key model outputs PCSK9 vaccines: predicted venues by scenario to 2030 PCSK9 vaccines: predicted revenues by region to 2030 PCSK9 vaccines: predicted volume to 2030 Patient numbers: PCSK9 vaccines versus anti-PCSK9 mAbs to 2030 Cardiovascular disease (CVD): background and epidemiology Cardiovascular disease: a major cause of death The economic burden of cardiovascular disease (US) The economic burden of cardiovascular disease (EU) Secondary causes of hyperlipidemia most commonly encountered in clinical practice Managing CVD: EU and US lipid guidelines – background Major changes in new US ATP IV guidelines Focus on CVD risk groups CVD risk groups: Heterozygous familial hypercholesterolemia (heFH) LDL-C treatment goals LDL-C treatment goals: comparing EU to US LDL-C treatment goals: ESC/EAS LDL-C treatment targets LDL-C treatment goals: intervention strategies by risk group/ LDL-C LDL-C lowering treatments Statins: lipid lowering intensity levels Drivers of statin choice Patient subgroups: statin benefits outweigh risks Side effects of statins LDL-C lowering treatment uptake: general Hospitalized CVD patients discharged on statin therapy, 1996-2006, by EU country LDL-C lowering treatment uptake: by risk group LDL-C goal achievement in CVD patients LDL-C goal achievement in heFH patients Anti-PCSK9 monoclonal antibodies: Novel LDL-C lowering agents Background to PCSK9 inhibitors PCSK9 role in LDL cholesterol (LDL-C) metabolism PCSK9 inhibition strategies

Continued.

PCSK9 monoclonal antibodies: current status
Broad target populations for anti-PCSK9 mAbs
PCSK9 monoclonal antibodies: overview of competitor activity
Sanofi Aventis - alirocumab (SAR236553)
Sanofi Aventis - alirocumab: Phase II data
Sanofi Aventis - alirocumab: ODYSSEY program
Sanofi Aventis - alirocumab: Phase III - ODYSSEY results
Submissions of alirocumab (SAR236553) - PraluentTM
PraluentTM - market opportunity (US/EU5/Japan)
Amgen - evolocumab (REPATHATM)
Evolocumab: example Phase III data (TESLA Part B)
Evolocumab: market opportunity (US/EU5/Japan)
Pfizer – bococizumab
Summary of anti-PCSK9 mAbs: outcomes studies
PCSK9 - other targetted therapies
Concerns with anti-PCSK9 monoclonals
Other remaining questions regarding PCSK9 inhibitors
PCSK9 vaccines: background and overview of R&D
PCSK9 vaccine: key model assumptions
The role of a PCSK9 vaccine
PCSK9 vaccine: Target Product Profile (TPP)
PCSK9 vaccine development - AFFiRiS AG
PCSK9 vaccine development – Pfizer
PCSK9 vaccine development – Pfizer (preclinical data)
Pros and cons of PCSK9 vaccine approach
PCSK9 vaccine: modelling commercial potential
Key model inputs: countries & target populations
Key model inputs: vaccine market penetration
Key model inputs: vaccine dosing/pricing
Key model inputs: vaccine discontinuation rate
Key model inputs: summary table
Methodology: definition of risk groups
Modelling methodology
Risk groups modelled
CVD hospital discharges
Death rates CHD
Coronary revascularisation (TCA and CABG combined), hospital discharges
Transluminal coronary angioplasty (TCA) and coronary artery bypass graft (CABG) discharges
Methodology: stroke incidence
Appendix: Anti-PCSK9 monoclonals: List of major clinical trials
ODYSSEY program - overview of Phase III trials
Phase III trials of evolocumab
Phase III trials of bococizumab
Bibliography
About VacZine Analytics
Disclaimer
PAGES: 90 MS PowerPoint slides, fully referenced/sourced. Available in .pdf form
Contents – Vaccine demand model TX vaccine (MS Excel-based)
Title sheet
CHARTS – VALUE
CHARTS – VOLUME
CHARTS – TREATED PATIENTS
Vaccine – Value Vaccine – Volume Patients – mAbs Secondary prevention Country worksheets  US Canada France Germany Italy Spain UK Other Europe Australia Source material  Key inputs Vaccine price summary Coronary revascularisation TCA CABG PAD Stroke US discharge trends heFH LDL-C goals WHO Statins in CVD patients Clinical trials Total population Back page
Worksheets 35 interconnected

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Third Report of the Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). Available at: http://www.nhlbi.nih.gov/guidelines/cholesterol/index.htm. Accessed: March 2013. 7. Stone NJ. 2013 ACC/AHA Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2014;63(25_PA):2889-2934. 8. Bell DA et al. Opportunistic screening for familial hypercholesterolaemia via a community laboratory. Ann Clin Biochem. 2012 Nov;49(Pt 6):534-7. 9. Benn M et al. Familial hypercholesterolemia in the Danish general population: prevalence, coronary artery disease, and cholesterol-lowering medication. J Clin Endocrinol Metab. 2012 Nov;97(11):3956-64. 10. Health Quality Ontario. Low-density lipoprotein apheresis: an evidence-based analysis. Ont Health Technol Assess Ser. 2007;7(5):1-101. 11. O'Kane MJ et al. The detection of heterozygous familial hypercholesterolemia in Ireland. Adv Ther. 2012 May;29(5):456-63. 12. Reddy G et al. LDL Lowering After Acute Coronary Syndrome: Is Lower Better? Curr Treat Options Cardiovasc Med. 2013 Feb;15(1):33-40. 13. Grundy SM et al. The Coordinating Committee of the National Cholesterol Education Program Implications of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel III Guidelines. Circulation. 2004.110(2):227–239. 14. Law MR et al. (2003) Quantifying effect of statins on low density lipoprotein cholesterol, ischaemic heart disease, and stroke: systematic review and meta-analysis. British Medical Journal, 326 (7404) :1423-29. 15. Weng TC et al. (2010) A systematic review and meta-analysis on the therapeutic equivalence of statins. Journal of Clinical Pharmacy and Therapeutics, 35(2):139-51. 16. Adams SP et al. Lipid lowering efficacy of atorvastatin. Cochrane Database Syst Rev. 2012 Dec 12;12:CD008226. 17. Guideline update. 2013 ACC/AHA Cholesterol Guidelines. Available at: http://www.hfs.illinois.gov/assets/ATP_IV_Handout.pdf. Accessed January 2015 18. Abramson JD, Rosenberg HD, Jewell N, Wright JM. Should people at low risk of cardiovascular disease take a statin?BMJ 19. Godlee F. Adverse effects of statins BMJ 2014; 348 doi: http://dx.doi.org/10.1136/bmj.g3306 (Published 15 May 2014) 20. McClure DL, Valuck RJ, Glanz M, Hokanson JE. Systematic review and meta-analysis of clinically relevant adverse events from HMG CoA reductase inhibitor trials worldwide from 1982 to present.Pharmacoepidemiol Drug Saf. 2007;16:132–43. 21. Kotseva K et al . Cardiovascular prevention guidelines in daily practice: a comparison of EUROASPIRE I, II, and III surveys in eight European countries. Lancet 2009;373(9667):929-40 22. Melloni C et al. Lipid-lowering intensification and low-density lipoprotein cholesterol achievement from hospital admission to 1- year follow-up after an acute coronary syndrome event: results from the Medications ApplIed aNd SusTAINed Over Time (MAINTAIN) registry. Am Heart J. 2010 Dec;160(6):1121-9, 1129.e1. 23. Siggaard-Andersen N et al. Only a fraction of patients with ischaemic diseases or diabetes are treated to recommended target values for plasma lipids. Dan Med J. 2012 Jul;59(7):A4470 24. Karalis DG et al. Use of Lipid-Lowering Medications and the Likelihood of Achieving Optimal LDL-Cholesterol Goals in Coronary Artery Disease Patients. Cholesterol. 2012;2012:861924. 25. Jones PH et al. Prevalence of dyslipidemia and lipid goal attainment in statin-treated subjects from 3 data sources: a retrospective analysis. J Am Heart Assoc. 2012 Dec;1(6):e001800. 26. Melloni C et al. Lipid-lowering intensification and low-density lipoprotein cholesterol achievement from hospital admission to 1- year follow-up after an acute coronary syndrome event: results from the Medications ApplIed aNd SusTAINed Over Time (MAINTAIN) registry. Am Heart J. 2010 Dec;160(6):1121-9, 1129.e1. 27. Javed U et al. Use of intensive lipid-lowering therapy in patients hospitalized with acute coronary syndrome: an analysis of 65,396 hospitalizations from 344 hospitals participating in Get With The Guidelines (GWTG). Am Heart J. 2010 Dec;160(6):1130-6, 1136.e1-3. 28. Ferrières J et al. Assessment of lipid-lowering treatment in France--the CEPHEUS study. Arch Cardiovasc Dis. 2008 Sep;101(9):557-63. 29. Huijgen R et al. Two years after molecular diagnosis of familial hypercholesterolemia: majority on cholesterol-lowering treatment but a minority reaches treatment goal. PLoS One. 2010 Feb 15;5(2):e9220. 30. Dragan S et al. Proprotein Convertase Subtilisin/Kexin 9 Inhibitors: An Emerging Lipid-Lowering Therapy? Journal of Cardiovascular Pharmacology and Therapeutics (2014) 1-12 31. Lambert G et al. Molecular basis of PCSK9 function. Atherosclerosis 2009; 203: 1-7 32. Lambert G et al. The PSCK9 decade. J Lipid Res 2012; 53:2515-24 33. Roche Pipeline Update. HY 2014. Available at: http://www.roche.com/irp2q14e-annex.pdf. Accessed January 2015 34. Payers fret about the next drug doomsday: Pricey PCSK9 cholesterol meds. May 7th 2014. 35. Pijlman AH, Huijgen R, Verhagen S, et al. Evaluation of cholesterol lowering treatment of patients with familial hypercholesterolaemia: a large cross-sectional study in the Netherlands. Atherosclerosis 2010;209(1):189-194 http://www.ncbi.nlm.nih.gov/pubmed/19818960 36. Pfizer Corporate Release. March 17th 2014. Bococizumab (RN316) Significantly Reduced LDL Cholesterol In Statin-Treated Adults With High Cholesterol In A Phase 2b Study1 37. Baruch A et al. Effect of RG7652, a mAb Against PCSK9, on Apolipoprotein B, Oxidized LDL, Lipoprotein(a) and Lipoprotein- Associated Phospholipase A2 in Healthy Individuals With Elevated LDL-c. Circulation.2013; 128: A12009. Abstract 12009 38. 31st Annual J. P. Morgan Healthcare Conference. Jan 8, 2013. Available at: http://investor.regeneron.com/events.cfm. Accessed: March 2013 39. IR Conference Call on PCSK9. SAR236553/REGN727 PCSK9 Antibody for Hypercholesterolemia. Phase 3 ODYSSEY Program Underway November 5, 2012. Available at: http://en.sanofi.com/investors/events/corporate/2012/2012-11-05_PCSK9_call.aspx. Accessed: March 2013 40. 33rd Annual JP Morgan Healthcare Conference, San Francisco US. Presentation by Elias Zerhouni. Available at: http://en.sanofi.com/Images/38086_JPM_2015_Presentation_FINAL.pdf. Accessed: January 2015 41. Raal FJ et al. Inhibition of PCSK9 with evolocumab in homozygous familial hypercholesterolaemia (TESLA Part B): a randomised, double-blind, placebo-controlled trial. The Lancet Vol 385, No 9965 p341-350 24th January 2015 42. Seeking Alpha Article by Stephen Barnes. Don't Underestimate Amgen: Part 2A, Cardiovascular And Oncology Pipeline Products Available at: http://seekingalpha.com/article/1975261-dont-underestimate-amgen-part-2a-cardiovascular-and-oncology-pipeline-products?page=2. Accessed January 2015 43. Pfizer Corporate Press Release. March 27th, 2014. Available at: http://press.pfizer.com/press-release/bococizumab-rn316- significantly-reduced-ldl-cholesterol-statin-treated-adults-high-cho. Accessed January 2015 44. McKenney JM et al. Safety and efficacy of a monoclonal antibody to proprotein convertase subtilisin/kexin type 9 serine protease, SAR236553/REGN727, in patients with primary hypercholesterolemia receiving ongoing stable atorvastatin therapy. J Am Coll Cardiol 2012;59:2344-53. 45. The PCSK9 decade: what will the future hold? June, 2014: 82nd Congress of the European Atherosclerosis Society, Madrid, Spain. Available at: http://www.eas-society.org/the-pcsk9-decade-what-will-the-future-hold.aspx. Accessed January 2015 46. Galabova G. et al. Affitope®-Based Active Immunization Targeting Pcsk9 For The Treatment Of Atherosclerosis. 80th EAS Congress, Milano, Italy, May 2012 47. Galabova G et al. Peptide-Based Anti-PCSK9 Vaccines - An Approach for Long-Term LDLc Management. PLOS one. PLoS One. 2014 Dec 4;9(12):e114469. 48. Pfizer developing PCSK9 pill, vaccine to lower cholesterol. Reuters News Article. January 2015. Available at: 49. WIPO: World Intellectual Property Organization. (WO2012131504) PCSK9 VACCINE, published October 2012 50. JMCP September 2010 - Academy of Managed Care Pharmacy. Available at: www.amcp.org/data/jmcp/September2010.pdf. Accessed: March 2013 51. Appendix E - National Institute for Health and Clinical Excellence. Available at: www.nice.org.uk/nicemedia/live/12048/41706/41706.pdf. Accessed: March 2013 52. Shah ND et al. Long-term medication adherence after myocardial infarction: experience of a community. Am J Med. 2009 Oct;122(10):961.e7-13. 53. Colivicchi F et al. Discontinuation of statin therapy and clinical outcome after ischemic stroke. Stroke. 2007 Oct;38(10):2652-7. 54. European Commission, Eurostat database. Available at: 55. OCED data. Health Care Utilisation MetaData : Surgical procedures by ICD-9-CM. Available at: http://stats.oecd.org/index.aspx?queryid=30167#. Accessed: March 2013 56. National Hospital Discharge Survey. Available at: http://www.cdc.gov/nchs/nhds/nhds_tables.htm. Accessed: March 2013 57. European Cardiovascular Disease Statistics 2012 edition. Available at: www.escardio.org/./advocacy/EuroHeart/Pages/2012- CVD-statistics.aspx. Accessed: March 2013 58. Bravata DM et al. Comparative Effectiveness of Percutaneous Coronary Interventions and Coronary Artery Bypass Grafting for Coronary Artery Disease [Internet].Rockville (MD): Agency for Healthcare Research and Quality (US); 2007 Oct. 59. SAR236553. Odyssey Program trials as of June 2014. Available at: www.odysseytrials.com. Accessed January 2015 60. Koren, M. J. et al. Anti-PCSK9 monotherapy for hypercholesterolemia—the MENDEL-2 randomized, controlled phase 3 clinical trial of evolocumab. J. Am. Coll. Cardiol.http://dx.doi.org/10.1016/j.jacc.2014.03.018. 61. Stroes, E. et al. Anti-PCSK9 antibody effectively lowers cholesterol in patients with statin intolerance: the GAUSS-2 randomized, placebo-controlled phase 3 clinical trial of evolocumab. J. Am. Coll. Cardiol. http://dx.doi.org/10.1016/j.jacc.2014.03.019. 62. Blom, D. J. et al. A 52-week placebo-controlled trial of evolocumab in hyperlipidemia. N. Engl. J. Med. 370, 1809–1819 (2014). 63. Robinson, J. G. et al. The LAPLACE-2 trial: a phase 3, double-blind, randomized, placebo and ezetimibe controlled, multicenter study to evaluate safety, tolerability and efficacy of evolocumab (AMG 145) in combination with statin therapy in subjects with primary hypercholesterolemia and mixed dyslipidemia. Presented at ACC Scientific Sessions (2014). 64. Raal, F. et al. The addition of evolocumab (AMG 145) allows the majority of heterozygous familial hypercholesterolemic patients to achieve low-density lipoprotein cholesterol goals—results from the phase 3 randomized, double-blind, placebo-controlled study [abstract 400-005]. Presented at ACC Scientific Sessions (2014). 65. US National Library of Medicine. ClinicalTrials.gov [online], (2014). 66. US National Library of Medicine. ClinicalTrials.gov [online], (2014). 67. US National Library of Medicine. ClinicalTrials.gov [online], (2014). 68. US National Library of Medicine. ClinicalTrials.gov [online], (2014). 69. US National Library of Medicine. ClinicalTrials.gov [online], (2014). 70. US National Library of Medicine. ClinicalTrials.gov [online], (2014). TERMS and CONDITIONS:
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About VacZine Analytics:
VacZine Analytics is an established strategic research agency based in the United Kingdom. Its aim is to provide
disease and commercial analysis for the vaccine industry and help build the case for developing new vaccines and
biologics.
For more information please visit our website www.vacZine-analytics.com VacZine Analytics (R) is a trading division of Assay Advantage Ltd, UK Company Number: 5807728
VacZine Analytics (R) and "the spiral logo" are UK Registered Trademarks, 2009

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