Progress in the Treatment of Cardiac Amyloidosis
|
|
- Sheryl Ethel Weaver
- 6 years ago
- Views:
Transcription
1 Progress in the Treatment of Cardiac Amyloidosis Jignesh Patel MD PhD FACC FRCP Director, Cardiac Amyloid Program Medical Director, Heart Transplant Program Clinical Professor Cedars-Sinai Heart Institute, Los Angeles, CA
2 Disclosures Alnylam Pharmaceuticals Research Grant (Revusiran) Pfizer Pharmaceuticals Research Grant (Tafamidis)
3 Major Amyloid Types and Causative Proteins Amyloid Types Light chain (AL) [Primary] Wildtype Transthyretin (ATTRwt) [ Senile ] Hereditary Transthyretin (ATTRm) [FAC/FAP*] Hereditary Apolipoprotein (AApoA1) Hereditary Fibrinogen (AFib) Isolated Atrial Amyloid (IAA) Secondary Amyloidosis (AA) Constituent Protein Subunits Immunoglobulin Light Chains Transthyretin - Wildtype Transthyretin with Mutation Apolipoprotein A1 mutations Fibrinogen mutations Atrial Natriuretic Peptide Amyloid Protein A *FAC = Familial Amyloid Cardiomyopathy FAP = Familial Amyloid Polyneuropathy 11/16/2017 3
4 Geographic Distribution and Age AL Cardiac Amyloidosis cases/year in US 11/16/2017 Sravan C. Penchala et al. PNAS 2013;110:
5 Therapeutic Targets for Amyloidosis
6 Suppression of TTR Drug Class Mechanism Antisense Oligonucleotides (ASO) Suppresses hepatic TTR mrna and serum TTR levels Small Interfering RNA (sirna) sirna bound to RNA-induced silencing complex (RISC) mediates cleavage of target mrna
7 Transthyretin levels for the single-dose cohorts in the ISIS-TTR Rx Phase 1 Study. Ackermann et al; Amyloid 2012, 19,
8 Effect of Revusiran on Serum TTR
9 ENDEAVOUR Study - Revusiran Study halted by Data Monitoring Committee: Deaths 17 revusiran 2 placebo (2:1 randomization) Majority due to HF Worsening neuropathy reported in Phase 2 follow up Development of Revusiran Discontinued (GalNAC conjugation) Patisiran (IV) studies ongoing for Familial Amyloid Polyneuropathy (FAP) (Lipid nanoparticle)
10 TTR Stabilization Drug Diflunisal Epigallocatechin-gallate (EGCG) Green Tea Tafamidis Mechanism NSAID: Binds and stabilizes common familial variants against acid-mediated fibril formation Inhibits fibril formation by directly binding to native unfolded peptides Binds to thyroid-binding sites of the TTR tetramer, inhibiting dissociation into monomers. Blocks rate-limiting step in the TTR amyloidogenesis cascade
11 Diflunisal Non-steroidal Anti-inflammatory (NSAID) Non-selective stabilizer of TTR tetramer Randomized, placebo-controlled study in FAP showed significant reduction in rate of neurological deterioration and improvement in quality of life in diflunisal treated patients 1 Japanese observational study in FAP reported sustained effects of diflunisal on both neurological and cardiac function, observing no deterioration in cardiac wall thickness or EF at 24 months 2 11/16/ Berk et al. JAMA : Sekijima Y et al. XIVth International Symposium on Amyloidosis; OP70 Indianapolis, USA, 2014:89 90.
12 Diflunisal Cautions: Renal dysfunction Fluid retention and worsening of HF Gastrointestinal bleeding
13 Tafamidis in TTR Cardiac Amyloid Phase 2 Study NT-ProBNP 6MWT Trop I Trop T Tafamidis treatment maintained TTR stabilization (98%) and was well tolerated. The absence of significant changes in most biochemical and echocardiographic parameters 20/28 preserved NYHA Class 15/31 further clinical events (CHF, AF, syncope) Maurer M et al. Circ HF 2015, (8); 3;
14 Safety and Efficacy of Tafamidis in Patients With Transthyretin Cardiomyopathy (ATTR-ACT) Phase 3 Primary Outcome Measures (30 months): All-cause mortality and frequency of cardiovascular-related hospitalization Enrollment: 400 Estimated Primary Completion Date: February 20, 2018 (Final data collection date for primary outcome measure)
15 Future Trials: AG10 TTR Stabilizer Penchala et al. PNAS 2013
16 Green tea halts progression of cardiac transthyretin amyloidosis: an observational report. N=19 Green Tea for 12 months Kristen AV et al. Clin Res Cardiol Oct;101(10): Epub 2012 May 15.
17 Fibril Degradation Drug Doxycycline-TUDCA Monoclonal anti-sap Antibodies Mechanism Removes already deposited amyloid Ab against a normal non-fibrillary glycoprotein SAP promotes a giant cell reaction that removes visceral amyloid deposits TUDCA Taursodeoxycholic Acid SAP Serum Amyloid P
18 Phase I/II Study of NEOD001 in Patients With Light Chain (AL) Amyloidosis and Persistent Organ Dysfunction Gertz MA et al. J Clin Oncol Apr 1;34(10):
19 NEOD001 Clinical Trials for Cardiac AL Amyloidosis PRONTO Study Primary Outcome Measures: Cardiac best response as measured by NTproBNP [ At 12 months ] Prior AL directed therapy with at least partial response Closed to recruitment VITAL Study Primary Outcome Measures: Time to composite of all-cause mortality or cardiac hospitalization Planned therapy with protoeosome inhibitor Closed to recruitment
20 Survival Survival post OHT for ATTR amyloidosis patients SRTR restrictive cardiomyopathy (N=206) 0.50 ATTR amyloidosis (N=16) 0.25 p= Time (years) Semigran, M, Patel J et al. iccat Registry
21 Survival Survival post OHT for AL amyloidosis patients SRTR restrictive cardiomyopathy (N=206) 0.50 AL amyloidosis (N=56) 0.25 p= Time (years) Semigran, M, Patel J et al. iccat Registry
22 Clinical and Biomarker Progression of TTR Cardiac Amyloidosis Castaño, A., Drachman, B.M., Judge, D. et al. Heart Fail Rev (2015) 20:
23 Summary The development of drugs for the treatment of amyloidosis has focused on specific targets Despite a variety of agents with potential therapeutic efficacy, progress in the cardiac arena has been slow. There is optimism for effective therapies in the future given the multitude of targets and therapies in the pipeline Development is restricted by costs in view of the limited market for a spectrum of orphan diseases Efficacy of treatment may depend upon early diagnosis
24
6/6/2017. Uncommon Etiologies of Heart Failure: Cardiac Amyloidosis. Objectives. Case Presentation
Uncommon Etiologies of Heart Failure: Cardiac Amyloidosis Maria Fe White, MSN, FNP/ACNP-BC, FHFSA, CHFN Lead Nurse Practitioner Advance Heart Programs Comprehensive Transplant Center Objectives Describe
More informationSummary of plenary sessions on October 31, 2015
4 th ATTR/Familial Amyloidosis Support Meeting October 31 to November 1, 2015 Hilton Chicago O Hare Airport hotel Summary of plenary sessions on October 31, 2015 1 Contents Welcome... 3 Why are we here?
More informationDaniel Judge presenting on behalf of the AG10 Phase 2 study investigators
Safety, Tolerability and Transthyretin Stabilization by AG10: A Phase 2, Randomized, Double-blind, Placebo-controlled Clinical Trial in Patients with Transthyretin Amyloid Cardiomyopathy and NYHA Class
More informationCorporate Medical Policy
Corporate Medical Policy File Name: Origination: Last CAP Review: Next CAP Review: Last Review: patisiran_onpattro 11/2018 n/a 5/2019 2/2019 Description of Procedure or Service is a double-stranded small
More informationESC 2018 Tafamidis Analyst Briefing. August 27, 2018
ESC 2018 Tafamidis Analyst Briefing August 27, 2018 1 Forward Looking Statements This presentation includes forward-looking statements about, among other things, a potential indication for Tafamidis for
More informationUpdate on Treatments for Systemic Amyloidosis
Update on Treatments for Systemic Amyloidosis Laura M. Dember, M.D. Renal, Electrolyte and Hypertension Division University of Pennsylvania ANZSN Update Course Darwin, Australia September 2, 2017 Disclosure
More information: A Study Examining the Prevalence of Transthyretin Mutations in Subjects Suspected of Having Cardiac Amyloidosis
: A Study Examining the Prevalence of Transthyretin Mutations in Subjects Suspected of Having Cardiac Amyloidosis 02 November 2015 1 Background and Rationale Cardiac amyloidosis is caused by extracellular
More informationEidos Therapeutics, Inc.
Eidos Therapeutics, Inc. Precision medicine for transthyretin amyloidosis September 2018 update Eidos forward-looking statements This presentation contains forward-looking statements about Eidos Therapeutics,
More informationA Problem with Cardiac Amyloidosis. Defining Amyloidosis. Typical Amyloid Heart. Definition of a double-blind study:
A disease caused by the deposition of a proteinaceous material, derived from the misfolded breakdown products of a normal or abnormal protein. Typical Amyloid Heart Defining Amyloidosis TYPEOF AMYLOID
More informationThe landscape of ATTR amyloidosis treatment
The landscape of ATTR amyloidosis treatment Teresa Coelho, M.D. Andrade s Center and Neurophysiology Department Hospital Santo António, Centro Hospitalar do Porto Portugal Disclosures Hospital Santo António
More informationNew approaches in amyloidosis. Philip Hawkins National Amyloidosis Centre UCL & Royal Free Hospital, London
New approaches in amyloidosis Philip Hawkins National Amyloidosis Centre UCL & Royal Free Hospital, London Systemic Amyloidosis Fatal protein misfolding/aggregation disease caused by accumulation of fibrillar
More information04 July 2016 ISA Uppsala, Sweden
Phase 2 Open-Label Extension (OLE) Study of Revusiran An Investigational RNAi Therapeutic for the Treatment of Patients with Transthyretin Amyloidosis with Cardiomyopathy 04 July 2016 ISA Uppsala, Sweden
More informationNEOD001 for amyloid light-chain (AL) amyloidosis
NIHR Innovation Observatory Evidence Briefing: October 2017 NEOD001 for amyloid light-chain (AL) amyloidosis NIHRIO (HSRIC) ID: 10617 NICE ID: 8803 LAY SUMMARY Amyloid light-chain (AL) amyloidosis is caused
More informationState of the Art Management of HFpEF
State of the Art Management of HFpEF Biykem Bozkurt, MD, FACC The Mary and Gordon Cain Chair & Professor of Medicine Medical Care Line Executive, DeBakey VA Medical Center, Director, Winters Center for
More informationCARDIAC AMYLOIDOSIS IMAGING ERIC MARTIN MD
CARDIAC AMYLOIDOSIS IMAGING ERIC MARTIN MD DISCLOSURES Bayer Dalcor Pharma UK LTD Harvard Clinical Research Institute Heartflow Inc. NIH Vascular Dynamics Employee-Iowa Heart Center/Mercy-Des Moines BACKGROUND
More informationSubject: Patisiran (Onpattro )
09-J3000-16 Original Effective Date: 12/15/18 Reviewed: 11/14/2018 Revised: 01/01/19 Subject: Patisiran (Onpattro ) THIS MEDICAL COVERAGE GUIDELINE IS NOT AN AUTHORIZATION, CERTIFICATION, EXPLANATION OF
More informationVarun Goel 1, Nathalie H Gosselin 2, Claudia Jomphe 2, Husain Attarwala 1, Xiaoping (Amy) Zhang 1, JF Marier 2, Gabriel Robbie 1
Population Pharmacokinetic (PK) / Pharmacodynamic (PD) Model of Serum Transthyretin (TTR) Following Patisiran Administration in Healthy Volunteers and Patients with Hereditary TTR-Mediated (hattr) Amyloidosis
More informationHereditary ATTR (hattr) Amyloidosis: Polyneuropathy An Overview. Identifying the link can lead to a crucial diagnosis
Hereditary ATTR (hattr) Amyloidosis: Polyneuropathy An Overview Identifying the link can lead to a crucial diagnosis Hereditary ATTR (hattr) Amyloidosis: Polyneuropathy Information about mechanism of disease,
More informationXiaoping (Amy) Zhang, Varun Goel, Husain Attarwala, and Gabriel Robbie. Alnylam Pharmaceuticals, Cambridge, USA
Patisiran Pharmacokinetics (PK), Pharmacodynamics (PD), and Exposure-Response (E-R) Relationship in Patients with Hereditary Transthyretin-Mediated (hattr) Amyloidosis Xiaoping (Amy) Zhang, Varun Goel,
More informationAmyloidosis: Challenges in Diagnosis and Management
Amyloidosis: Challenges in Diagnosis and Management Ronald Witteles, MD Co-Director, Stanford Amyloid Center Associate Professor of Cardiovascular Medicine Program Director, Internal Medicine Residency
More informationDiagnosis of Amyloidosis. Maria M. Picken MD, PhD Loyola University Medical Center Chicago
Diagnosis of Amyloidosis Maria M. Picken MD, PhD Loyola University Medical Center Chicago mpicken@lumc.edu 1 Outline Diagnosis of amyloidosis Fat pad Other 2 Amyloidoses protein folding disorders protein
More informationPrimary Amyloidosis. Kihyun Kim Div. of Hematology/Oncology, Dept. of Medicine, Sungkyunkwan Univ. School of Medidine Samsung Medical Center
Primary Amyloidosis Kihyun Kim Div. of Hematology/Oncology, Dept. of Medicine, Sungkyunkwan Univ. School of Medidine Samsung Medical Center Systemic Amyloidosis A group of complex diseases caused by tissue
More informationSAFETY AND EFFICACY OF INOTERSEN IN PATIENTS WITH HEREDITARY TRANSTHYRETIN AMYLOIDOSIS POLYNEUROPATHY (hattr-pn) Teresa Coelho, MD
SAFETY AND EFFICACY OF INOTERSEN IN PATIENTS WITH HEREDITARY TRANSTHYRETIN AMYLOIDOSIS POLYNEUROPATHY (hattr-pn) Teresa Coelho, MD Centro Hospitalar do Porto Porto, Portugal Disclosures Hospital Santo
More informationTTR-FAP: Diagnosis and treatment Zürich June 19,2014. Ole B Suhr Umeå University and University Hospital Department of Medicine Umeå Sweden
TTR-FAP: Diagnosis and treatment Zürich June 19,2014 Ole B Suhr Umeå University and University Hospital Department of Medicine Umeå Sweden Diagnosis of ATTR amyloidosis Clinical symptoms of ATTR- amyloidosis
More informationFAMILIAL AMYLOID POLYNEUROPATHY (TTR-FAP): Genetics and Treatment
FAMILIAL AMYLOID POLYNEUROPATHY (TTR-FAP): Genetics and Treatment Michelle Mezei BSc (Pharm), MDCM, FRCPC Neuromuscular Diseases Unit, VGH Division of Neurology, UBC 1 Learning Objectives To become familiar
More informationSelection of Transthyretin Amyloid Inhibitors. Irina Iakovleva
Selection of Transthyretin Amyloid Inhibitors Irina Iakovleva Department of Medical Biochemistry and Biophysics Umeå 2016 Responsible publisher under swedish law: the Dean of the Medical Faculty This work
More informationMayo Clinic, Rochester, Minnesota; 2 Tufts Medical Center, Boston, Massachusetts; 3
NEOD001 Demonstrates Organ Biomarker Responses in Patients With Light Chain Amyloidosis and Persistent Organ Dysfunction: Final Results From a Phase 1/2 Study Morie A. Gertz, 1 Raymond L. Comenzo, 2 Heather
More informationHereditary ATTR (hattr) Amyloidosis: Cardiomyopathy An Overview. Identifying the link can lead to a crucial diagnosis
Hereditary ATTR (hattr) Amyloidosis: Cardiomyopathy An Overview Identifying the link can lead to a crucial diagnosis Hereditary ATTR (hattr) Amyloidosis: Cardiomyopathy Information about mechanism of disease,
More informationAmyloidosis: What to do and how to diagnose: An Update 2017
Amyloidosis: What to do and how to diagnose: An Update 2017 Jonathan L. Kaufman, MD Associate Professor Hematology & Oncology Winship Cancer Institute of Emory University Amyloidosis Protein Conformation/Deposition
More informationSafety and Efficacy of Inotersen in Patients with Hereditary Transthyretin Amyloidosis with Polyneuropathy (NEURO-TTR) Annabel K.
Safety and Efficacy of Inotersen in Patients with Hereditary Transthyretin Amyloidosis with Polyneuropathy (NEURO-TTR) Annabel K. Wang, MD University of California, Irvine ANA 2017 October 17, 2017 San
More informationUpdate in Nuclear Imaging of Amyloidosis and Sarcoidosis
Update in Nuclear Imaging of Amyloidosis and Sarcoidosis Balaji Tamarappoo MD, PhD, Cedars-Sinai Heart Institute and Biomedical Imaging Research Institute Cedars-Sinai Medical Center Los Angeles, CA, USA.
More informationIMAGING IN CARDIAC AMYLOIDOSIS ; TRENDS IN DIAGNOSIS AND GUIDING THERAPY
IMAGING IN CARDIAC AMYLOIDOSIS ; TRENDS IN DIAGNOSIS AND GUIDING THERAPY Mohamed Abo Mandour, MD. Al-Azhar University Cardiac amyloidosis is an under appreciated cause of HF The bottom line pathologic
More informationCLINICAL/THERAPEUTIC APPROACHES TO THREE SPECIFIC CARDIOMYOPAHIES: MYOCARDITIS, AMYLOIDOSIS, AND NON-COMPACTION
CLINICAL/THERAPEUTIC APPROACHES TO THREE SPECIFIC CARDIOMYOPAHIES: MYOCARDITIS, AMYLOIDOSIS, AND NON-COMPACTION G. William Dec, MD, FACC Massachusetts General Hospital Harvard Medical School American College
More informationreversing familial amyloid polyneuropathy naturally the raw vegan plant based detoxification regeneration workbook for healing patients volume 2
DOWNLOAD OR READ : REVERSING FAMILIAL AMYLOID POLYNEUROPATHY NATURALLY THE RAW VEGAN PLANT BASED DETOXIFICATION REGENERATION WORKBOOK FOR HEALING PATIENTS VOLUME 2 PDF EBOOK EPUB MOBI Page 1 Page 2 healing
More informationEducation Brochure. Hereditary ATTR amyloidosis A closer look at an inherited condition
Education Brochure Hereditary ATTR amyloidosis A closer look at an inherited condition What is hereditary ATTR (hattr) amyloidosis? hattr amyloidosis is caused by a gene change (mutation) that affects
More informationNeurologic Manifestations of Systemic Disease (N Scolding and C Rice, Section Editors)
Curr Treat Options Neurol (2016) 18:53 DOI 10.1007/s11940-016-0436-z Neurologic Manifestations of Systemic Disease (N Scolding and C Rice, Section Editors) Current and Future Treatment Approaches in Transthyretin
More informationAmyloid Transthyretin (ATTR) Amyloidosis AN OVERVIEW
Amyloid Transthyretin (ATTR) Amyloidosis AN OVERVIEW AMYLOID TRANSTHYRETIN (ATTR) AMYLOIDOSIS ATTR amyloidosis is a rare, progressive, and fatal disease that manifests clinically with motor and sensory
More informationManagement of Heart Failure in Older Adults
Management of Heart Failure in Older Adults New Data, New Guidelines, New Challenges JOSE NATIVI, MD, MSCI Assistant Professor of Medicine Cardiovascular Director Amyloidosis Program DISCLOSURES - Advisory
More informationPhase 2 Open-Label Extension Study of Patisiran An RNAi Therapeutic for the Treatment of Familial Amyloidotic Polyneuropathy
Phase 2 Open-Label Extension Study of Patisiran An RNAi Therapeutic for the Treatment of Familial Amyloidotic Polyneuropathy American Neurological Association Annual Meeting October 13, 2014 Agenda Welcome
More informationMore%Than%Just%Coronary%Artery Disease
More%Than%Just%Coronary%Artery Disease Thomas%D.%Gossios Cardiomyopathies%Laboratory AUTH%1st%Cardiology%Department,%AHEPA%Hospital First&presentation Male,&67&years&old Present&condition Typical&angina&at&rest.
More informationAmyloidosis- What does it have to do with Myeloma? Anita D Souza, MD, MS Froedtert & MCW Cancer Center Milwaukee, WI
Amyloidosis- What does it have to do with Myeloma? Anita D Souza, MD, MS Froedtert & MCW Cancer Center Milwaukee, WI Objectives Types of amyloidosis How does amyloidosis form? How is amyloidosis diagnosed?
More informationAmyloidosis. Philip Hawkins National Amyloidosis Centre UCL & Royal Free Hospital, London
Amyloidosis Philip Hawkins National Amyloidosis Centre UCL & Royal Free Hospital, London Amyloid Abnormal extracellular fibrillar protein deposit in tissues Pathognomonic red-green birefringence after
More informationASSESSMENT OF CARDIAC AMYLOIDOSIS BY USING 18F-SODIUM FLUORIDE PET/MR IMAGING.
ASSESSMENT OF CARDIAC AMYLOIDOSIS BY USING 18F-SODIUM FLUORIDE PET/MR IMAGING. R. Abgral, M.Trivieri, M. Dweck, P. Robson, N. Karakatsanis, A. Lala, J. Contreras, R. Gopalan, P. Gorevic, V. Fuster, J.
More informationAmyloidosis Information. A General Overview for Patients
Amyloidosis Information A General Overview for Patients www.amyloidosis.org Amyloidosis was first discovered 150 years ago by the well know German pathologist, Dr. Rudolf Virchow. Although the disease
More informationDiagnosis and management of transthyretin familial amyloid polyneuropathy in Japan: red-flag symptom clusters and treatment algorithm
Sekijima et al. Orphanet Journal of Rare Diseases (2018) 13:6 DOI 10.1186/s13023-017-0726-x REVIEW Diagnosis and management of transthyretin familial amyloid polyneuropathy in Japan: red-flag symptom clusters
More informationFocus on cardiac amyloidosis. Overview. Others cause chamber enlargement and wall thinning. ECG or echo often doesn t fit the usual etiologies
Infiltrative Cardiomyopathies Focus on cardiac amyloidosis Van N Selby, MD Assistant Professor of Medicine UCSF Advanced Heart Failure and Heart Transplant Program October 9, 2015 Overview Infiltrative
More informationOrgan Transplantation for Cardiac Amyloidosis
Organ Transplantation for Cardiac Amyloidosis Marc J. Semigran MD Medical Director Heart Failure and Cardiac Transplantation Massachusetts General Hospital Associate Professor of Medicine Harvard Medical
More informationCharacterizing the effect of transthyretin amyloid on the heart
Boston University OpenBU Theses & Dissertations http://open.bu.edu Boston University Theses & Dissertations 2015 Characterizing the effect of transthyretin amyloid on the heart Koch, Clarissa https://hdl.handle.net/2144/16195
More information2017 ASG Biannual Meeting Notes
2017 ASG Biannual Meeting Notes Chicago (O'Hare Hilton Hotel), 2017-10-28 Contents Agenda... 5 Friday Night Meet and Greet... 6 Saturday Meeting (Grand Ballroom)... 6 Sunday... 6 Welcome Muriel & Dr. Gertz...
More informationCardiac Amyloidosis: The Zebra is Losing its Stripes
Internal Medicine Grand Rounds University of Texas Southwestern Medical Center February 1 st, 2019 Cardiac Amyloidosis: The Zebra is Losing its Stripes Justin L. Grodin, MD, MPH, FACC, FHFSA Assistant
More informationA Guide to Transthyretin Amyloidosis
A Guide to Transthyretin Amyloidosis Authored by Teresa Coelho, Bo-Goran Ericzon, Rodney Falk, Donna Grogan, Shu-ichi Ikeda, Mathew Maurer, Violaine Plante-Bordeneuve, Ole Suhr, Pedro Trigo 2016 Edition
More informationConference Call to Discuss FDA Approval of ONPATTRO (patisiran)
Conference Call to Discuss FDA Approval of ONPATTRO (patisiran) August 10, 2018 1 Agenda Welcome Christine Lindenboom Vice President, Investor Relations & Corporate Communications Introduction John Maraganore,
More informationΕφαρμογή των νεώτερων κατευθυντήριων οδηγιών στην καρδιακή ανεπάρκεια σε αρρώστους με αμυλοείδωση
Εφαρμογή των νεώτερων κατευθυντήριων οδηγιών στην καρδιακή ανεπάρκεια σε αρρώστους με αμυλοείδωση Γεράσιμος Φιλιππάτος Β Πανεπιστημιακή Καρδιολογική Κλινική Αττικόν Νοσοκομείο Disclosures Chair or Committee
More informationAPOLLO Phase 3 Study of Patisiran Complete Results
Leo Living with hattr Amyloidosis APOLLO Phase 3 Study of Patisiran Complete Results November 2, 2017 Agenda Welcome Christine Lindenboom Vice President, Investor Relations & Corporate Communications Introduction
More informationUpdate on systemic amyloidosis Dr Ashutosh Wechalekar
Update on systemic amyloidosis Dr Ashutosh Wechalekar Reader in Haematology and Medicine University College London UK Amyloidosis SAP GAG s IL- 6 mediated release Serum Amyloid A Oligomers Mis-folding
More informationAmyloidoses are a heterogeneous group of disorders
REPORT Hereditary ATTR Amyloidosis: Burden of Illness and Diagnostic Challenges Morie A. Gertz, MD, MACP Amyloidoses are a heterogeneous group of disorders with a variety of clinical presentations characterized
More informationStepwise Approach for the Diagnosis of Amyloid Heart Disease
Stepwise Approach for the Diagnosis of Amyloid Heart Disease Mat Maurer, MD Columbia University Medical Center Arnold and Arlene Goldstein Professor of Cardiology April 13, 2019 Disclosures I am under-funded
More informationCardiology Pearls for the Hospitalist
Cardiology Pearls for the Hospitalist Ronald Witteles, M.D. Stanford University School of Medicine October 20, 2018 @Ron_Witteles A common patient scenario It might seem standard but Can we do better?
More informationFourth Quarter and Full Year 2018 Financial Results February 7, 2019
Fourth Quarter and Full Year 2018 Financial Results February 7, 2019 1 2019 Alnylam Pharmaceuticals, Inc. Agenda Welcome Christine Lindenboom Vice President, Investor Relations & Corporate Communications
More informationYES NO UNKNOWN. Stage I: Rule-Out Dashboard Secondary Findings in Adults ACTIONABILITY PENETRANCE SIGNIFICANCE/BURDEN OF DISEASE NEXT STEPS
Stage I: Rule-Out Dashboard GENE/GENE PANEL: TTR DISORDER: Hereditary transthyretin-related amyloidosis HGNC ID: 12405 OMIM ID: 105210 ACTIONABILITY PENETRANCE 1. Is there a qualifying resource, such as
More informationClinical Profile FOR. Indication. Important Safety Information
Clinical Profile FOR The first and only FDA-approved RNAi treatment for the polyneuropathy of hereditary transthyretin-mediated amyloidosis in adults. 1 Indication ONPATTRO (patisiran) is indicated for
More information2017 ASG Biannual Meeting Questions and Answers
2017 ASG Biannual Meeting Questions and Answers From Chicago (O'Hare Hilton Hotel), 2017-10-29, plus doctors' written responses to submitted questions that were not answered at the meeting. Contents Causes
More informationST2 in Heart Failure. ST2 as a Cardiovascular Biomarker. Competitive Model of ST2/IL-33 Signaling. ST2 and IL-33: Cardioprotective
ST2 as a Cardiovascular Biomarker Lori B. Daniels, MD, MAS, FACC Professor of Medicine Director, Coronary Care Unit University of California, San Diego ST2 and IL-33: Cardioprotective ST2: member of the
More informationReview of Systemic Amyloidosis 김기현 성균관의대삼성서울병원
Review of Systemic Amyloidosis 김기현 성균관의대삼성서울병원 김기현 Amyloidosis A heterogeneous group of diseases bound by the characteristic deposition of amyloid fibrils in soft tissues Amyloid fibril protein nomenclature:
More informationHereditary ATTR amyloidosis Talking to your healthcare professional about a hereditary condition
Healthcare Professional Discussion Guide Hereditary ATTR amyloidosis Talking to your healthcare professional about a hereditary condition This guide will give you some tips and strategies to help you start
More informationSilenceurs et inhibiteurs (oligonucléotides antisens) d ARNm dans les neuropathies amyloides héréditaires à transthyrétine : c est parti!
Silenceurs et inhibiteurs (oligonucléotides antisens) d ARNm dans les neuropathies amyloides héréditaires à transthyrétine : c est parti! V. Planté-Bordeneuve Service de Neurologie Réseau Amylose CHU Henri
More informationRepurposing Diflunisal for Familial Amyloid Polyneuropathy A Randomized Clinical Trial
Research Original Investigation Repurposing Diflunisal for Familial Amyloid Polyneuropathy A Randomized Clinical Trial John L. Berk, MD; Ole B. Suhr, MD, PhD; Laura Obici, MD; Yoshiki Sekijima, MD, PhD;
More informationThe Approach to Patients with Heart Failure and Mid-Range (40-50%) Ejection Fraction (HFmrEF)
The Approach to Patients with Heart Failure and Mid-Range (40-50%) Ejection Fraction (HFmrEF) 22 nd Annual Heart Failure 2018 an Update on Therapy April 21, 2018 Los Angeles, CA Barry Greenberg, M.D. Distinguished
More informationForms Revision: Myeloma Changes
Sharing knowledge. Sharing hope. Forms Revision: Myeloma Changes J. Brunner, PA-C and A. Dispenzieri, MD February 2013 Disclosures Janet Brunner, PA-C I have no relevant conflicts of interest to disclose.
More informationAlnylam Assist: Screening for Familial Amyloidotic Polyneuropathy (FAP) in TTR Amyloidosis
FREE Screening Program* Alnylam Assist: Screening for Familial Amyloidotic Polyneuropathy (FAP) in TTR Amyloidosis Alnylam Pharmaceuticals, Inc. is committed to advancing the diagnosis and treatment of
More informationCardiac amyloidosis : An update on diagnosis and treatment
JOSEPH P. DONNELLY, MD Department of Cardiovascular Medicine, Heart and Vascular Institute, Cleveland Clinic MAZEN HANNA, MD Department of Cardiovascular Medicine, Heart and Vascular Institute, Cleveland
More informationNews and Stories - Winter 2019
News and Stories - Winter 2019 Untangling Amyloidosis Symposium at ASH Conference The American Society of Hematology held its annual meeting in San Diego, California the first week of December, 2018. Over
More informationCardiac Involvement is Underdiagnosed in Patients with Biopsy-Proven Systemic AL Amyloidosis
Original Article 41 Cardiac Involvement is Underdiagnosed in Patients with Biopsy-Proven Systemic AL Amyloidosis Haoyi Zheng 1, Amitabha Mazumder 2, Stuart D. Katz 3 1. Cardiac Imaging, The Heart Center,
More informationC. Quarta, L. Obici, S. Longhi, S. Perlini, A. Milandri, F. Del Corso, F. Perfetto, F. Cappelli, G. Merlini, C. Rapezzi
Hereditary transthyretin-related amyloidosis with exclusively cardiac phenotype: disease profile and differential diagnosis with hypertrophic cardiomyopathy and senile systemic amyloidosis C. Quarta, L.
More informationFrequencies and geographic distributions of genetic mutations in transthyretinand non-transthyretin-related familial amyloidosis
Clin Genet 2015: 88: 396 400 Printed in Singapore. All rights reserved Short Report Frequencies and geographic distributions of genetic mutations in transthyretinand non-transthyretin-related familial
More informationRecognizing and Treating Amyloidosis in Heart Failure Patients. Denise Barnard, M.D., F.A.C.C. 18 th Annual HF Symposium
Recognizing and Treating Amyloidosis in Heart Failure Patients Denise Barnard, M.D., F.A.C.C. 18 th Annual HF Symposium Disclosures: None Lecture Outline What is Amyloidosis? What forms of amyloid affect
More informationTreating HF Patients with ARNI s Why, When and How?
Treating HF Patients with ARNI s Why, When and How? 19 th Annual San Diego Heart Failure Symposium for Primary Care Physicians January 11-12, 2019 La Jolla, CA Barry Greenberg M.D. Distinguished Professor
More informationCorporate Presentation
Corporate Presentation Disclaimer Statements in this presentation that are not descriptions of historical facts are forward looking statements within the meaning of the safe harbor provisions of the Private
More informationManaging Atrial Fibrillation in the Heart Failure Patient
Managing Atrial Fibrillation in the Heart Failure Patient Jonathan S. Steinberg, MD Professor of Medicine (adj) University of Rochester School of Medicine & Dentistry Director, Arrhythmia Institute Valley
More informationAmyloidosis: Incidence, Prognosis, Investigation and Management
Amyloidosis: Incidence, Prognosis, Investigation and Management Jennifer Helen Pinney Doctor of Medicine University College London UK National Amyloidosis Centre Department of Medicine Royal Free Hospital
More informationClinical history. 73 yo man with chest pain Systemic hypertension and WG Stress EKG N Stress echocardiogram: Cardiac catheterization: no CAD
CASE 8 Clinical history 73 yo man with chest pain Systemic hypertension and WG Stress EKG N Stress echocardiogram: Concentric hypertrophy Hypokinesis of LV-Inf Cardiac catheterization: no CAD Technique
More informationAmyloidosis and Waldenström s Macroglobulinemia
Amyloidosis and Waldenström s Macroglobulinemia Morie A. Gertz, Giampaolo Merlini, and Steven P. Treon Primary systemic amyloidosis is an immunoglobulin light chain disorder that is 1/5th as common as
More informationDiagnostic approach to cardiac amyloidosis: A case report
Diagnostic approach to cardiac amyloidosis: A case report Georgia Vogiatzi, MD, MSc, PhD 1 st Cardiology Department, Hippokration Hospital, Athens Medical School Disclosures I have no relevant relationships
More informationActa Neurologica Belgica Single-centre experience on transthyretin familial amyloid polyneuropathy: case series and literature review
Acta Neurologica Belgica Single-centre experience on transthyretin familial amyloid polyneuropathy: case series and literature review --Manuscript Draft-- Manuscript Number: Full Title: Article Type: Corresponding
More informationNT-proBNP: Evidence-based application in primary care
NT-proBNP: Evidence-based application in primary care Associate Professor Rob Doughty The University of Auckland, Auckland City Hospital, Auckland Heart Group NT-proBNP: Evidence in Primary Care The problem
More informationProthena Corporation plc Overview
November 11, 2014 Prothena Corporation plc Overview 2014 Credit Suisse HC Conference The Arizona Biltmore Phoenix, AZ Forward-Looking Statements This presentation contains forward-looking statements. These
More informationAt Fox Chase Cancer Centre during study participation
Long-Term Outcome of a Phase 1 Study of the Investigational Oral Proteasome Inhibitor Ixazomib at the Recommended Phase 3 Dose in Patients with Relapsed or Refractory Systemic Light-Chain (AL) Amyloidosis
More informationPage 1. Typical presentation. Unexpected Clinical Presentation of Cardiac Amyloidosis. Typical presentation. Typical presentation
Unexpected Clinical Presentation of Cardiac Amyloidosis Typical presentation Sx assoicated with Lt sided HF and/or Rt sided HF Dae-Won Sohn, M.D., Ph.D., FACC, FASE Department of Internal Medicine, Seoul
More informationEvaluation of Myocardial Changes in Familial Amyloid Polyneuropathy after Liver Transplantation
ORIGINAL ARTICLE Evaluation of Myocardial Changes in Familial Amyloid Polyneuropathy after Liver Transplantation Sadahisa Okamoto 1, Taro Yamashita 1, Yukio Ando 2, Mitsuharu Ueda 2, Yohei Misumi 1, Konen
More informationBiomarker-guided HF: What have we learned (so far)?
Biomarker-guided HF: What have we learned (so far)? James L. Januzzi, Jr, MD, FACC, FESC Associate Professor of Medicine Harvard Medical School Director, Cardiac ICU Massachusetts General Hospital DECLARATION
More informationSheena Surindran Grand Rounds 2/15/11
Sheena Surindran Grand Rounds 2/15/11 Affects 5 12 person per million / year 5 10% associated with myeloma Median survival without treatment is 12 40 months Most commonly affected organs are kidney, heart
More informationHeart Failure in Women: Dr Goh Ping Ping Cardiologist Asian Heart & Vascular Centre
Heart Failure in Women: More than EF? Dr Goh Ping Ping Cardiologist Asian Heart & Vascular Centre Overview Review pathophysiology as it relates to diagnosis and management Rational approach to workup:
More informationMulticenter Study of Planar Technetium 99m Pyrophosphate Cardiac Imaging Predicting Survival for Patients With ATTR Cardiac Amyloidosis
Research JAMA Cardiology Original Investigation Multicenter Study of Planar Technetium 99m Pyrophosphate Cardiac Imaging Predicting Survival for Patients With ATTR Cardiac Amyloidosis Adam Castano, MD,
More informationAmyloidosis and the Heart
Patient Information Amyloidosis and the Heart What are the symptoms of heart failure? Introduction In some patients with amyloidosis there is a build-up of amyloid deposits in the heart muscle. This may
More informationNew in Heart Failure SGK autumn session 2012
New in Heart Failure SGK autumn session 2012 Roger Hullin Cardiology Department of Internal Medicine Centre Universitaire Hospitaler Vaudois University of Lausanne ESC Heart Failure Guidelines 2012 Classes
More informationOverview & Update on the Utilization of the Natriuretic Peptides in Heart Failure
June 28, 2016 Overview & Update on the Utilization of the Natriuretic Peptides in Heart Failure Linda C. Rogers, PhD, DABCC, FACB. Agenda Overview of the Natriuretic Peptides and Efficacy studies Similarities
More informationCAELUM BIOSCIENCES. Corporate Overview May, 2017
CAELUM BIOSCIENCES Corporate Overview May, 2017 Forward Looking Statements Statements in this presentation that are not descriptions of historical facts are forward looking statements within the meaning
More informationLCZ696 A First-in-Class Angiotensin Receptor Neprilysin Inhibitor
The Angiotensin Receptor Neprilysin Inhibitor LCZ696 in Heart Failure with Preserved Ejection Fraction The Prospective comparison of ARNI with ARB on Management Of heart failure with preserved ejection
More informationClinical trials evaluating potential therapies for light chain (AL) amyloidosis
Expert Opinion on Orphan Drugs ISSN: (Print) 2167-8707 (Online) Journal homepage: http://www.tandfonline.com/loi/ieod20 Clinical trials evaluating potential therapies for light chain (AL) amyloidosis Eli
More information