Elan Corporation

4,539 views

Published on

0 Comments
5 Likes
Statistics
Notes
  • Be the first to comment

No Downloads
Views
Total views
4,539
On SlideShare
0
From Embeds
0
Number of Embeds
25
Actions
Shares
0
Downloads
0
Comments
0
Likes
5
Embeds 0
No embeds

No notes for slide

Elan Corporation

  1. 1. Elan Corporation plc. Advancing science, changing lives 1
  2. 2. Safe Harbor This is an independent study performed by students from the Faculté des Sciences Pharmaceutiques of Lille. The opinions expressed are our own and not necessarily those of Elan Corporation plc. 2
  3. 3. Overview of the company • Created on 18 December 1969 by Donald Panoz • Became a public limited company in January 1984 • Stock Exchange Listings – New York Stock Exchange (ELN) – Irish Stock Exchange (ELN.I) • Elan Corp = 2 business units: Elan Drug Technology BioNeurology BioPharmaceuticals Integrated technology Science and clinical based • Oral Controlled Release • Parkinson’s disease • NanoCrystal technology • Alzheimer’s disease • Multiple sclerosis 3
  4. 4. Locations and subsidiaries in 2009 OCR NanoCrystal Others Dublin • Leased • Headquarters • 41,000 sq. ft King of Prussia • Leased Athlone • R&D • Owned • manufacturing, sales • R&D • administration • manufacturing San Francisco, CA • 113,000 sq. ft • administration • 463,000 sq. ft • Leased • R&D Bermuda Gainesville, GA • sales Financial services • Owned • administration company • R&D • 334,000 sq. ft • manufacturing • administration • 89,000 sq. ft http://www.elandrugtechnologies.com/locations 4 Annual Report 2009
  5. 5. Elan Drug Technology’s pipeline 5 Elan website
  6. 6. Elan BioNeurology’s pipeline Discovery Pre-clinical Phase I Phase II Phase III Marketed Parkinson’s Bapineuzumab Bapineuzumab Tysabri AAB-002 ELND006 SC IV research (US/UE) Natalizumab Autoimmune ELND007 (Myelome ACC-001 LY450139 Tysabri US research multiple) Gamma ELND004 ELND005 Prialt secretase Natalizumab Alzheimer’s disease ELND002 SC Azactam Multiple sclerosis Crohn’s disease Chronic pain Maxepime Other 6 Elan website
  7. 7. Elan Drug Technology  History with Donald Panoz  NanoCrystal and Oral Controlled Release  Yesterday : Tricor, Skelaxin, Ritalin, Verelan  Today : Ampyra, Invega Sustenna, Zypadhera  Tomorrow ?
  8. 8. 1969 • Donald Panoz,, moves to Ireland and launches Elan Corporation. 1978 • Elan opens a research and development center in Athlone, Ireland 1984 • Elan floats its U.S. subsidiary on the NASDAQ 1990 • Elan absorbs its U.S. subsidiary and launches a full public offering on the New York, London, and Irish Stock Exchanges. • The company acquires a manufacturing operation in Lugano, 1993 Switzerland. 1995 • The company acquires a manufacturing facility in Israel. • New strategic direction as a full-scale pharmaceuticals company with 1996 the acquisition of Athena Neuroscience in the United States 1998 • Elan acquires GWC Health and Neurex. • Elan's stock collapses after the Securities and Exchange Commission 2002 launches an investigation into the company's accounting practices.8 • AN 1792: meningo-encephalitis
  9. 9. Business Overview Expertise in drug formulation, development, scale-up & manufacture • More than 30 products launched in 100+ countries • 15 products in clinical development • Extensive product development, scale-up and manufacturing capabilities in US and EU World’s leading drug delivery company • 40 years of innovation and expertise in drug delivery • Most successful drug delivery provider in US in recent times – 11 products launched since 2001 Robust drug delivery portfolio in the industry 9
  10. 10. Elan collaborative model 10 Elan website
  11. 11. What is Nanocrystal Technology ?  Technology using tiny drug particles in the nanometre scale  The drug size is reduced by a proprietary milling technique  GRAS stabilisers are absorded on the nanoparticle to afford agglomeration Objective: obtain a  GRAS stabilizers must be safe and are excipients commonly used in colloïdal dispersion marketed products ( fat acid, polymers) 11 Elan website
  12. 12. Effects of NaoCrystal on biovailability • Nanocrystal technology is used:  For poorly water soluble drugs: ↑ solubility ↑ bioavailability  For moderately soluble drugs when high concentration is need in a low fluid volume • Useful for all dosages forms both parenteral and solid ,liquid oral dosage forms 12
  13. 13. Point on Oral Controlled Release Avinza, Cardizem, Naprelan Verelan Afeditab Focalin, Ritalin, Verelan, Luvox, Zanaflex 13
  14. 14. Yesterday… Trade name Generic name Indication Technology Parteners Tricor® 145mg fenofibrate Dyslipidemia NanoCrystal Skeletal-muscular Skelaxin® metaxolone NanoCrystal pain Ritalin® Methylphenidrate/ OCR Hyperactivity / Focalin® Dexmethylphenidate (SODAS) OCR Verelan® verapamil Cardiac disorders (CODAS) 14
  15. 15. Tricor® : what’s that? • API: micronised fenofibrate (prodrug) • Indications: Dyslipidemia type IIa, IIb, IV, III,V • 2004: Tricor® 145 launched by Abbott and manufactured by Elan using NanoCrystal technology • Could market lower dosage strength with 9% improve in bioavailability • Minimised food effect:  Class formulation: 30-50% fasting Vs 60-90% while eating  Micronized formulation: bioavailability 100% without conditions. • Patented formulation expiry on 9-Jan-2018 15
  16. 16. Today… Trade name Generic name Indication Technology Parteners Paliperidone Schizophrenia NanoCrystal palmitate Fosaprepitant Emetogenic NanoCrystal dimeglutine chemotherapy Olanzapine Schizophrenia NanoCrystal OCR Fampridine Cardiac disorders (MXDAS) 16
  17. 17. Ampyra® (Fampridine) : What is it ? • FDA approval on 22 jan 2010 • Indication : improved walking in patients with multiple Sclerosis • Extended released tablets using Oral release technology MXDAS • Mechanism = not fully elucidated => ® several hypotheses for Ampyra’s mechanism:  Fampridine is a broad spectrum potassium channeblocker  Fampridine increases conduction of action potentials in demyelinated axons through inhibition of potassium channels  Increase acetylcholine release at the neuromuscular junction 17
  18. 18. Ampyra: the deal Elan and Accorda, a joint venture since 1998 for MS US$35.7millions from Accorda for the drug delivery Biogen paid: upfront: US$ 110 millions milestones: US$400 millions 16% of royalties for elan manufacture in Athlone’s facility rest of the world marketing http://seekingalpha.com/article/184252-acorda-after-fda-approval-what-s-next-for-ampyra 18 http://www.iguanabio.com/acorda-biogen-in-ex-us-deal-for-fampridine-sr-no-us/
  19. 19. Ampyra®’s forecast sales • Represents the sales in U.S • Ampyra will be launched in March 2010 19
  20. 20. … and tomorrow for Elan Drug Technology 20 Elan website
  21. 21. Elan NeuroBiology – Yesterday : Azactam®/Maxipime®, Prialt® – Today : Tysabri ® – Tomorrow : • Alzheimer Immunotherapy Program • Research in Parkinson’s disease 21
  22. 22. Timeline of Elan of market products 1995 • Maxipime® (Cefepime) • Azactam® (Aztreonam) 1996 • Tysabri® (Natalizumab) 1998 • Prialt® (Ziconotide) 2000 • AIP Program • From 1969 to early 1990’s : Elan only worked in drug delivery domains • Then, Elan’s activities widened with collaboration from research to market of drugs • Beginning of a new business unit called Elan Biopharmaceuticals 22
  23. 23. Maxipime® (cefepime) : what’s that? • Semi-synthetic forth-generation cephalosporin • Mechanism of action : – Inhibits final transpeptidation of peptidoglycan synthesis in bacterial cell walls – inhibiting cell wall biosynthesis • Broad spectrum activity • Indications – respiratory tract infection – skin infections – urinary tract infections – febrile neutropenia – Intra-abdominal infections The product was The basic U.S. patent launched worldwide in for Maxipime expired 1995 in March 2007. Elan acquired US Stop distributing comarketing rights Maxipime as of from BMS in January September 30, 2010. 23 1999
  24. 24. Maxipime® (cefepime) revenues 180 150 USD (Millons) USD (Millions) 120 90 - 78% 60 30 0 Bristol-Myers Squibb Co Elan Corp plc 24 Annual report 2009 Thomson
  25. 25. Prialt® (ziconotide) 25
  26. 26. Prialt® (ziconotide) : what’s that? Member of the ω conotoxin family o 25 aminoacids and 3 disulfide bonds Pain o prepared by chemical synthesis Transmitting nerves Pain signal Targets N-Type voltage sensitive calcium channels = > diminished neurotransmitter release Ziconotide Intrathecal formulation N-type calcium channel Calcium 26
  27. 27. History of Prialt® (ziconotide) May Neurex (now Elan) joined Warner-Lambert (now Pfizer) in a collaboration to cooperate in the development 1993 and commercialization of ziconotide for the treatment of brain ischemia early phase II trials for the prevention of brain damage halted due to some patients experiencing hypotension. 1995 Neurex received permission from the FDA in May 1995 to resume these trials Aug. 9th World Congress on Pain meeting in Vienna, Austria : results of a placebo controlled study into the use of 1999 intrathecal ziconotide in the treatment of chronic pain in opioid-resistant non-cancer patients May 37th ASCO meeting in San Francisco : clinical data for chronic pain in cancer and AIDS patients 2001 9 Jul. Orphan designation granted by the European Commission 2001 Feb. Elan had reached an agreement with the FDA and had agreed to conduct one additional phase III 2002 2004 Pain Management 2004 meeting in London, UK 4th annual conference on Ion Channels in Drug Discovery Development in Philadelphia, PA. Apr. Lauch market in the USA 2005 Mar. Eisai acquired the European rights to ziconotide from Elan 2006 Elan received ~ $60 million for the launch in key European markets +$40 million contingent on Prialt achieving revenue related milestones in Europe. 2016 Expiration of fundamental U.S. patent covering the use of ziconotide 27 Thomson
  28. 28. Tysabri® (natalizumab) 28
  29. 29. Tysabri® (natalizumab) : what is it ? • Humanized Monoclonal Antibody (recombinant IgG4) • Targets selectively human α4-integrine • Trade names : Tysabri®, Antegren® Integrines α-4 • Expressed on cell membrane • In association with β1 or β7 integrines • Adherence molecules on activated T-cells, B- cells, monocytes, eosinophils, basophils, leukocytes , NK cells, dendritic cells, and vascular endothelium of some organs. • Implicated in leukocytes homing to CNS and GIT 29
  30. 30. Tysabri® dealings 1996 August 2000 Elan entered into a worldwide exclusive Elan was collaborating with collaboration with Biogen for the joint Axogen on the development of development, manufacture and natalizumab commercialization of natalizumab. 1999 23-Nov-2004 Elan acquired Axogen Initially approved by FDA for treatment of RRMS. 30
  31. 31. Tysabri®’s timeline 23-Nov-2004 25-Feb-2005 05-Jun-2006 FDA approval for Voluntary FDA approved a special treatment of relapsing suspension of restricted distribution forms of MS Tysabri market program for Tysabri (TOUCH®) 18 MONTHS 18-Feb-2005 Mar- 2006 Jul-2006 Biogen learnt about 1 REMS presented to Tysabri’s reintroduction case of death to PML FDA : advisory panel to the market and 2 suspected cases voted to support the of PML drug’s return Drug Discovery Today Volume 12, Numbers 13/14 July 2007 31 Nature Biotechnology, Nov 2009,vol 27, Numero 11
  32. 32. Tysabri® and PML • 25-Feb-2006: Confirmation of 3 cases of PML (initial trials: 3,417 patients)  2 patients during MS trial (SENTINEL) + 1 patient in trial for Crohn’s disease  All 3 were on combination therapy with another immunosuppressive drug  No patients on Tysabri alone developed PML • Progressive Multifocal Leucoencephalitis = opportunistic disease  Agent = JC virus (Polyomavirus family)  infects oligodendrocyts => local demyelinisation => neurologic dysfunction  ~ 80% of population already met JCV before adult age => latent form (bone marrow and kidneys) • Natalizumab + another immune drug  fixation of natalizumab on VCAM-1 and MAdCAM-1 of endothelial cells  inhibition of T-cells homing  uncontrolled replication of JCV in CNS 32
  33. 33. 33
  34. 34. Consequences on the stock 28-Mar-2005 25-Mar-2005 8,00 $ 26,90 $ -67% ELAN 25-Mar-2005 28-Mar-2005 67,28 $ 38,65 $ BIOGEN -50% 34
  35. 35. Tysabri®’s REMS: TOUCH® program • 7-8 March 2006 : Risk Minimalisation Action Plan exposed to Peripheral and Central Nervous System Drugs Advisory Committee Meeting => Goals : o Warn patients about risk-benefit balance forTysabri use in treatment of MS patients. o Contraindicated in immunocompromised patients o Minimize health consequences of PML (death/disability) through early diagnosis • Key elements of Tysabri Outreach: Unified Commitment to Health program o Mandatory enrollment of prescribers, infusion sites, and afflilated central pharmacies o Controlled distribution to authorized infusion sites and pharmacies o Education program for health care providers and patients o Safety surveillance of PML, serious opportunistic infections, and deaths o Program evaluation of health outcomes, process compliance, and assessment of knowledge 35
  36. 36. The benefit • Natalizumab versus β-IFN is: - Sligthly more effective (MRI data) - Twice as effective (relapse-rate data) - More effective (EDSS data) • Many people strongly believe that Natalizumab is the most effective drug we currently have. • Patients asked the right to choose and accept the risk Tysabri returned to the US market in July 2006 36
  37. 37. Top 5 Multiple Sclerosis Drugs in 2007 (m$) N°5 !  Will Tysabri marketing setback affecting its own sales and Elan’s business ? 37
  38. 38. Tysabri® sales rose, fell… then rise again! Total Tysabri revenues Elan corp revenues 350,0 300,0 250,0 200,0 150,0 100,0 50,0 0,0 Forecast Tysabri in-market net sales in 2013 : 1,3 b$ NB: Expected patent expiry by 2015 Life cycle management: natalizumab SC extension of indication to multiple myeloma Nature Biotechnology, novembre 2009, vol 27, numero 11 Business Insights, 2009 38 Natalizumab, Thomson 2009 JP Morgan 220210
  39. 39. Existing and Emerging Therapies for MS 2005 2006 2007 2010 2011 2012 2013 Injectables Orals BG 12 Oral Oral Fumarate Cladribine Rebif Teriflunomide Betaseron FTY 720 Laquinimod Copaxone Fampridine SB683699 ambulation indication? Avonex IV Novantrone IV Campath Tysabri Rituximab II - RRMS; III - PPMS Generic Mitoxantrone Daclizumab (oncology) (MS) MBP 8298 MLN1202 approved In phase II In phase III Filed 39
  40. 40. Alzheimer’s disease 40
  41. 41. The Alzheimer Immunotherapy Program Alzheimer Immunotherapy Program Research, develop Main product: and commercialize Bapineuzumab selective products Includes multiple compounds being evaluated for slowing the progression of Alzheimer's disease. 41 http://www.ihsglobalinsight.com/SDA/SDADetail17223.htm
  42. 42. Two approaches for Alzheimer’s disease Mécanismes Moléculaires dans les Démences Neurodégénératives Inserm-UM2-EPHE U710 La maladie d’Alzheimer : aspects moléculaires, diagnostiques et thérapeutiques 42 Octobre 2009
  43. 43. Figure 6 Neuropsychopharmacology (2009) 34, 142–158; doi:10.1038/npp.2008.115
  44. 44. Three Approaches to Disrupting the Beta Amyloid Cascade Preventing production Clearing existing beta of beta amyloid in the amyloid from the brain with secretase brain inhibitors Preventing aggregation of beta amyloid in the brain (ELND005) 44
  45. 45. Tomorrow : AIP Gamma secretase Beta ELND006 amyloid anti ELND007 aggregation Follows-on ELND005 P75 AIP Janssen Alzheimer Bapineuzumab modulator ACC-001 Immunotherapy Follows-on Bapineuzumab ACC-001 Beta Follows-on secretase 45 JP Morgan 2009
  46. 46. The Deal $885 M 18,4% Elan's capital $ 500 M IP Elan (AIP) Estimated at $500 M 49,9% Janssen AI's capital Royalties Under conditions 46 BioCentury, the Berstein report on biobusiness July 6, 2009 Page A22 of 37 http://www.ihsglobalinsight.com/SDA/SDADetail17223.htm
  47. 47. The Deal Transaction J&J purchased 107.3 million Elan's shares at $8,241/share J&J also agreed not to acquire any more shares for the next five years Royalties : ONLY after J&J has earned profits from the AIP equal to its $500 M Janssen AI: all annual in-market sales Royalties for Elan $2 billion - $4 billion 5% $4 billion - $ 10 billion 7% > 10 billion 9% The program will remain partnered with Wyeth, which was acquired by Pfizer Inc (01/2009, $68 billion) 47 BioCentury, the Berstein report on biobusiness July 6, 2009 Page A22 of 37
  48. 48. Bapineuzumab (AAB-001) • Name: AAB-001 • Other Name: Bapineuzumab • Class: Humanized monoclonal antibody • Therapeutic Applications: Mild to moderate AD • Therapy Types: Protein : humanized monoclonal antibody against Aβ • Mechanisms: Designed to bind and remove the Aβ peptide that accumulates in the brain • Development Status: Fast Track status from FDA in U.S • FDA Phase: Phase III • Side Effects: – Passive immunotherapy will induce similar side effects is largely unknown. One report has shown that frequency and severity of cerebral microhemorrhage – Vasogenic edema 48
  49. 49. Bapineuzumab (AAB-001) : Phase III Design Multicentrique, randomized, double-blind, placebo- controlled, parallel-assigned trial, studies 4 studies : 2 with ApoE4 (+) & 2 withApo E4 (-) 2 US trials and 2 European phase III trial Safety Objective The safety and tolerability Estimated study Duration 18 Months Dosing 0.5 mg/kg 1 mg/kg Development Fast Track designation from the FDA Source : http://www.elan.com/Images/Bapineuzumab%20_AAB-001_%20Backgrounder%20Final_tcm3-20147.pdf http://clinicaltrials.gov/ct2/show/NCT00574132?term=bapineuzumab&rank=1 http://clinicaltrials.gov/ct2/show?term=bapineuzumab&rank=4 49
  50. 50. Forecast sales and market share for bapineuzumab 50
  51. 51. Research on Parkinson’s disease • Several active early discovery efforts in Parkinson’s disease • The Michael J. Fox Foundation for Parkinson’s Research Program « Novel Approaches to Drug Discovery » • In 2009, the program funded six research projects. • 2006 : Michael J. Fox Foundation and Elan Commit up to $2 Million to Drive Novel Therapies for Parkinson's Annual report 2009 51 MJFF website
  52. 52. Our opinion about Elan Corporation plc. • Financial Analysis • SWOT • Would we join Elan? 52
  53. 53. Major owners of Elan Corp. at 22-Feb-10 Janssen Pharmaceuticals 18,4% Shareholders Fidelity Management 50,3% and Research Company 13,0% Wellington Management 5,9% T. Rowe Price 4,1% Westfield Capital All directors and Norges Bank (The Management officers as a group Central 3,2% (18 persons) Bank of Norway) 2,0% 3,1% 53
  54. 54. Total product revenue for 2009 106 m$ 38,4% 61,6 m$ 22,3% 34,9 m$ 32,6 m$ 12,6% 11,8% 22,1 m$ 18,7 m$ 8,0% 6,8% 0 m$ 0,0% EDT business 24,8% 724,3m$ BioNeurology 86,5% business 75,2% 81,4m$ 16,5 m$ 13,2m$ 1,7m$ 9,7% 2,0% 1,6% 0,2% 54 Annual Report 2009
  55. 55. Revenues from marketed products of BioNeurology 900 800 700 600 500 Maxipime Prialt 400 Azactam 300 Tysabri 200 100 0 2004 2005 2006 2007 2008 2009 55 Annual Report
  56. 56. Elan Drug Technology: total revenue 350 300 250 Focalin XR / Ritalin LA 200 Skelaxin Verelan 150 Tricor Other 100 50 0 2004 2005 2006 2007 2008 2009 56 Annual Report
  57. 57. Five years performance : EBITDA improvement Adjusted EBITDA 150 100 50 USD (millions) 0 -50 -100 -150 -200 -250 2005 2006 2007 2008 2009 57 Annual Report
  58. 58. Operating margin 50 31,9 0 2005 2006 2007 2008 2009 -50 USD (millions) -100 -150 -143,5 -164,4 -200 -198,5 -250 -265,3 -300 58 Annual Report
  59. 59. The Balance Sheet 2008 2009 US$m US$m Assets Current Assets Cash and cash equivalents 375.3 836.5 Restricted cash and cash equivalents -- current 20.2 16.8 Investment securities -- current 30.5 7.1 Deferred tax assets -- current 95.9 23.9 Other current assets 240.1 274.9 Total current assets 762.0 1,159.2 Non-Current Assets Intangible assets, net 553.9 417.4 Property, plant and equipment, net 351.8 292.8 Equity method investment -- 235.0 Investment securities -- non-current 8.1 8.7 Deferred tax assets -- non-current 145.3 174.8 Restricted cash and cash equivalents -- non- 15.0 14.9 current Other assets 31.5 42.9 Total Assets 1,867.6 2,345.7 Liabilities and Shareholders' Equity/(Deficit) Accounts payable, accrued and other liabilities 334.8 311.5 Long-term debt 1,765.0 1,540.0 Shareholders' equity/(deficit) (232.2) 494.2 Total Liabilities and Shareholders' 1,867.6 2,345.7 59 Annual Report Equity/(Deficit)
  60. 60. Elan’s debt 2005-2009 Elan's long term debt 2500 2000 Due dates : millions USD 1500 • November 2011:3OO m USD • December 2013: 615 m USD 1000 • October 2016: 625 m USD 500 0 2005 2006 2007 2008 2009 Strong indebtedness => the success of AIP is essential Elan plc is restricted among various other things : • Incur additional debt • Enter into transactions with related parties Widen • Enter into some types of investment transactions; their capital • Engage in some asset sales or sale and leaseback transactions • Pay dividends or buy back our ordinary shares • Consolidate, merge with, or sell substantially all our assets to another entity 60 Annual Report
  61. 61. 61 Annual Report
  62. 62. Five years performance : cost management Operating expenses (m$) Approximate 5 700,0 years change 600,0 500,0 232,0 220,0 262,9 323,4 400,0 293,6 ↑ > 30% 300,0 200,0 360,0 359,0 339,3 292,7 268,2 100,0 ↓ > 20% 0,0 2 005 2 006 2 007 2 008 2 009 SG&A expenses R&D expenses  Reduced SG&A and reinvest savings in R&D 62 Annual Report
  63. 63. Number of employees in Elan corp. Number of employees in Elan corp. 700 600 500 R&D activities 400 Manufacturing and supply activities Sales and marketing activities 300 General and administrative area 200 100 0 2005 2006 2007 2008 2009 R&D Manufacturing and Sales and General and Year Total activities supply activities marketing activities administrative area 2005 471 583 310 365 1729 2006 494 543 328 369 1734 2007 553 547 211 299 1610 2008 656 601 123 307 1687 63 Annual Report
  64. 64. Elan’s lawsuits 2002 2009 Elan vs Wolf Elan/J&J vs Popper LLP Biogen 2008 Elan vs Shareholders 64
  65. 65. Evolution of the stocks AN1792 + Launch Results of of Tysabri Bapineuzumab Wolf popper LLP CT 65 Tysabri withdrawal
  66. 66. Strengths Weaknesses •Leadership position in drug delivery Important endebtedness •Tysabri, its key product, sustaining the revenue growth •patent expiry and risk of generic competition •Strategic alliances bolstering the company’s business •Geographic concentration enhancing business risk •Tysabri marketing restricted indications affecting Elan’s business Elan Corp. Opportunities Threats • Focus on Alzheimer’s market, could be a source of • Intense competition from Avonex, Rebif against revenues Tysabri in the MS drug market. •Benefits to accrue from growing incidences of •Patent expiries could affect company’s Revenues neurological disorders •Legal proceedings could affect company’s •Favorable demographic shift increasing Alzheimer drug Reputation market •Reimbursement policies could affect company’s product sale 66
  67. 67. Conclusion • An important debt and short due dates. • Cash flow left only for 12 months!… • Tysabri revenues will not be enough. • No more constant revenues from BioNeurology business unit. • Elan depends on the success of the AIP, especially on bapineuzumab success . • So ?… 67
  68. 68. Thanks for your attention! Any question? 68
  69. 69. Fibrates : Mechanism of action  Excrétion cholestérol et acides biliaires  ß-oxydation fibrates  Apo-A1, Apo-A2 ( HDL)  LPL, Apo-CIII PPAR-α  TG synthesis  HDL PPAR-α RXR  VLDL  Serum homocysteine*  risk of venous thrombosis  ß -oxydation  LPL 69
  70. 70. Molecular basis of the activity of fibrates Activation by exogeneous ligands, e.g. fibrates Regulation of the heterodimerisation expression of genes (liver, heart, vessels) PPAR-α RXR Biological effects Lipid metabolism, athéroscleros is, inflammation (?) PPRE Peroxysome Proliferator Responsive Elements 70
  71. 71. Dyslipidemia classification 71

×