Autoimmune Hemolytic Anemia - CAD Market Brief (071213)

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Disease briefing of autoimmune hemolytic anemia - CAD.

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Autoimmune Hemolytic Anemia - CAD Market Brief (071213)

  1. 1. By  Will  Roettger   Principal  Consultant   20/20  Market  Insights,  LLC   July  12,    2013  
  2. 2. Will  Roettger  is  an  established  career  professional  in  the  pharmaceutical  and   biotech  industry.  Having  worked  for  Novartis,  AstraZeneca,  Merck,  Alexion,  and   Dendreon  he  has  developed  expertise  across  the  therapeutic  areas  of  oncology,   hematology,  and  immunology  for  pipeline  and  launch  products.  He  has  been   instrumental  in  establishing  marketing  intelligence  as  a  core  capability  in   support  of  clinical  and  commercial  new  product  development,  solving  the  many   commercial  challenges  that  high-­‐priced  specialty  products  face  from  a  patient,   provider,  and  investor  perspective.  Additionally  he  has  supported  two  specialty   product  launches,  providing  actionable  insights  and  recommendations  by   integrating  market  research  findings  with  competitive  intelligence.  As  a   principal  for  20/20  Market  Insights,  LLC,  he  is  dedicated  to  providing  clients  with   clear  vision  into  competitor  landscapes,  strategies,  and  product  assessments   that  drive  strategic  business  decisions  in  new  drug  development.   Contact  Information:   Will  Roettger   Principal  Consultant   20/20  Market  Insights,  LLC   908-­‐391-­‐4362   will.roettger@gmail.com   2  
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  5. 5. AIHA  is  the  immunologic  destruction  of  RBCs  mediated  by  auto-­‐antibodies  against  antigens  on   the  RBC  surface.  They  are  classified  by  isotype  (IgG,  IgM,  IgA)  and  the  temperature  at  which  they   maximally  react   5  
  6. 6. Acquired  Hemolytic  Anemia   Immune  Hemolytic  Anemia   (most  common  form)   Non-­‐Immune  Hemolytic  Anemia   !  !  !  (1:80,000)   Autoimmune  (AIHA)   (1:300,000)   (50%)   !  Idiopathic   !  PCH   Alloimmune   !  !  (1:100,000)   Cold  Antibody   (13-­‐25%)   Primary     Drug  Induced   Infection  Induced   Mechanical  Trauma   Paroxysmal  Nocturnal   Hemoglobinuria  (PNH)   MAHA  (TTP,  HUS,  aHUS)   Toxins   Secondary     (50%)   !  Infectious   Mononucleosis   !  Lymphoma   Warm  Antibody     (50-­‐70%)   !  Idiopathic  (ITP)   !  Systemic  Lupus   Erythematosus  (SLE)   !  Evan’s  Syndrome   Hemolytic  Disease   of  the  Newborn   (HDN)   Blood  Transfusion   Reactions   Sources:  Kelton,  AHA  10.  ICD-­‐10  Disease  of  Blood  D55-­‐D59.  http://en.wikipedia.org/ wiki/Acquired_hemolytic_anemia.  Haematologica  2006;  91:460-­‐466   6  
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  10. 10. Source:  Acquired  Hemolytic  Syndrome,  Chapter  10,  JG  Kelton.  J.  Rogers,   UNC  Internal  Medicine,  GR  Slides,  2008   10  
  11. 11. Source:  Acquired  Hemolytic  Syndrome,  Chapter  10,  JG  Kelton.  J.  Rogers,   UNC  Internal  Medicine,  GR  Slides,  2008   11  
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  13. 13. Source:  AHA  10   13  
  14. 14. Intravascular Hemolysis Extra-vascular Hemolysis Mechanism Red cell destruction in the intravascular compartment resulting in hemoglobin being released into the plasma Red cells are recognized as foreign or become more rigid and are sequestered in the spleen with subsequent phagocytosis Possible Causes Complement, toxins, membrane defects, enzyme deficiencies, drugs Immunoglobulin, complement, membrane defects •  Hemoglobinemia Present Absent/present in severe cases •  Hemoglobinuria Present Absent/present in severe cases •  Haptoglobin Reduced or absent Normal or Reduced •  Methemalbumin Present Absent •  Hemosidinuria Present Absent •  LDH Grossly elevated Elevated •  Jaundice Present Present •  Splenomegaly Absent Present •  Blood Film Schistocytes. Helmet cells, fragmented red cells Spherocytes, erythrophagocytosis Laboratory Feature Source:  AHA  10   14  
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  17. 17. Rituxan  (375  mg/m2)  +  Fludarabine  (40  mg/m2)  –  Berensten,  et.al.  2010   Response Level Frequency Hb Level IgM Concentration (Median, g/dL) (Median, % of Baseline) (n) (%) 22 76 CR 6 21 +4.0 -81 PR 16 55 +3.1 -76 NR 7 24 -0.2 -27 29 100 +2.5 -71 Response Rate TOTAL Median Time To Response: 4 months Response Duration: >66 months Grade 3-4 Hematologic Toxicity: 41% •  CR  =  absence  of  anemia  ,  no  signs  of  hemolysis,  no  clinical  symptoms  of  CAD,  undetectable  serum  monoclonal  protein,  and  no  signs  of   clonal  lymphyproliferation  by  bone  marrow  histology,  immunohistochemistry  and  flow  cytometry.   •  PR  =  stable  increase  in  Hb  levels  by  at  least  2.0  g/dL  or  to  the  normal  range,  combined  with  a  reduction  in  serum  IgM  concentrations  by  at   least  50%  or  to  the  normal  range,  improvement  of  clinical  symptoms,  transfusion  independency   •  NR  =  patients  not  meeting  CR  or  PR.   Source:  NCT00373595  (Blood  2010;116(17):3180-­‐3184   17  
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  20. 20. Will  Roettger   Principal  Consultant   20/20  Market  Insights,  LLC   908-­‐391-­‐4362   will.roettger@gmail.com   20  
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