WFH 03019 TEMPLATES

1
Innovations Treatments for Rare Bleeding
Disorders Paula Bolton-Maggs Chair, WFH Rare
Bleeding Disorders Committee 2007 Global Forum
2
Innovations?

• More information about the rare disorders
• Improvements in current products
• Licensing
• Modifications with regard to viral inactivation
  and half-life
• New products in development

3
WFH Data on Rare Bleeding Disorders

• Global surveys begun 1998
• First report 1999
• Now annual
• Seeks information on
• Basic demographics
• Resources for care and treatment
• Prevalence of infectious complications (HCV, HIV)

4
WFH Data on Rare Bleeding Disorders
WFH Global Survey Data Each year questionnaires
are sent to national haemophilia associations
linked with the WFH with the request that they in
turn work with physicians or health officials, as
necessary, to complete the survey. The WFH
reviews the completed questionnaires for
inconsistencies, which are clarified where
possible by communicating directly with the
participating organization. The quality of the
data from different countries is variable
5
WFH Data on Rare Bleeding Disorders

• Enhance Access to Treatment for von Willebrand
  Disease, Rare Factor Deficiencies, and Inherited
  Platelet Disorders
• we will
• Improve diagnosis and enhance data collection on
  their prevalence by country
• Collaborate with regulators and industry to
  enhance access to safe treatment
• Expand training, educational materials, and
  web-based resources
• WFH Strategic Plan, 2006 - 2010

6
WFH Data on Rare Bleeding Disorders
New Global Survey questions for 2005
For 2006 split into GT, BSS and other
7
2006 WFH Global Survey Summary
8
Data from successive WFH Global Surveys
9
(No Transcript)
10
Some issues

• Quality of data
• Are countries reporting only cases with severe
  deficiency?
• Clearly some countries are reporting mild
  deficiency as well as severe

11
WFH Data on Rare Bleeding Disorders
Reflects UK register
Countries Reporting gt100 Patients
Source WFH Global Survey 2004
12
Rare Bleeding disorders Global Survey 2006
1 in 2 million
1 in 500,000
13
Variable distribution in different parts of the
world
14
(No Transcript)
15
What products are manufactured?

• FV deficiency no concentrate use
  virally-treated FFP
• Octaplas pooled from approx 1500 donations, SD
  treated, sourced from Austria, Germany and USA
• Methylene-blue treated single donor units UK

16
Fibrinogen Treatment products

• Unlicensed virally inactivated concentrates
• CSL Behring
• SNBTS
• LFB
• Half life 3-5 days
• Tranexamic acid
• Cryo is a good source but not virally inactivated

17
Treatment for FII

• Beriplex PN (CSL) contains II, VII, IX and X
• DEFIX HT (SNBTS) contains II, IX and X
• Prothromplex T (Baxter) with factor VII
• Kaskadil (LFB) with VII
• Octaplex (Octapharma) with VII

18
Treatment Products FVII

• rVIIa is the treatment of choice although little
  data
• Factor VII concentrates (LFB and Baxter)
• Factor IX concentrates containing FVII
• (FFP)
• A level of 10-15 u/dl is probably sufficient for
  surgery

19
Factor X Treatment Products

• No factor X concentrate
• Intermediate purity Factor IX concentrates
• Increased risk of thrombosis
• (FFP)
• A level of 10-25 u/dl is probably sufficient for
  surgery
• People with levels gt10 u/dl probably require no
  replacement therapy

20
Therapeutic options in FXI deficiency

• Fresh frozen plasma (Virally treated)
• Factor XI concentrates (BPL, LFB) but
  thrombogenic
• Fibrinolytic inhibitors very effective for
  dental extractions
• Fibrin glue main experience in Israel
• Desmopressin - unconvincing
• rVIIa risk of thrombosis

21
Factor XIII deficiency

• Prophylaxis long half life 11-14 days
• Pasteurised plasma-derived concentrate available
  from CSL Behring (Fibrogammin-P)
• Give 1000 units every 5-6 weeks which raises
  level to 30-35 u/dl (NB assay problems)
• Platelets contain FXIII and in an emergency may
  be useful.

22
What innovations?

• GOOD NEWS! But it is secret
• Several companies are developing new products for
  rare disorders
• rXIII (NN)
• Pd V (Kedrion) and rV (Crucell)
• Plasminogen concentrate for ligneous
  conjunctivitis (Kedrion)
• rVWF (Baxter)
• ADAMTS13 (Baxter)
• Companies are seeking further evidence about
  pharmacokinetics
• Fibrinogen concentrate (CSL Behring)
• FXI concentrate (LFB)

23
WFH Data on Rare Bleeding Disorders and Patient
Registries
Thank you
24
Fibrinogen products
25
Products for FVII deficiency
26
Products for FX (and FII) deficiency
27
Products for FXI deficiency