Presented to the 10th Global Forum of the World Federation of Hemophilia November 2017

1. Access to haemophilia care
Post humanitarian aid
Albert Farrugia
Adjunct Professor, School of Surgery, University of Western Australia
Senior Scientific and Regulatory Advisor, Kedrion S.p.A
The 10th WFH Global Forum on Research and Treatment Products for Bleeding Disorders
Montreal – November 8 - 10, 2017

2. DISCLOSURES FOR:
(SPEAKER NAME)
Conflict Disclosure - if conflict of interest exists
Research Support None
Director, Officer, Employee Senior Director of Biologics consulting company
Shareholder None
Honoraria None
Advisory Committee None
Consultant Consultant to manufacturers of haemophilia
therapies

3. G l o b a l v o l u m e o f p l a s m a f o r f r a c t i o n a t i o n 1 9 9 0 - 2 0 1 4
R e c o v e r e d a n d S o u r c e –
To t a l Vo l u m e i n 2 0 1 4 : 4 5 M i l l i o n l i t r e s

4. Worldwide demand for FVIII 1984 – 2014
Plasma - D er iv e d , Million IUs
4

5. Estimates
• In 2014, 45 Million Litres of plasma were collected.
• Using current technology, a yield of 200 IU of FVIII per litre is expected.
• This would result in 9 billion IU (the current total amount of FVIII provided globally)
• 4 billion IU of pd VIII were actually provided
• It is clear that around half the possible amount of FVIII is not being converted into
concentrate.
• In contrast, similar estimates for other products indicate that approximately 85% of
the available IG (probably an underestimate) and albumin are being extracted

6. Conver genc e of players
The Italian exampl e – Septem ber 2017
6
http://www.centronazionalesangue.it/node/582
• 750,000 IU of Factor VIII exceeding the regional and national
requirements.
• Made available by the Lombardy Region.
• Provides for cooperation:
• Developing standards for optimum use of blood components in
Armenia
• Introduction of a blood collection system and components from
voluntary and unpaid donors based on the Italian model.
• Research projects and exchange of information.
• Technical support and logisitics provided by Kedrion.
• Based on the agreement of the Italian Regions of 7 February 2013 for the
promotion and implementation of cooperation agreements for the export
Memorandum of Cooperation
between the Italian National Blood
Center and the Ministry of Health of
Armenia signed on 6 June.

7. In recent years, over 10 million units of factors have been donated
by Italy to countries such as Afghanistan, Albania, Armenia and
India.
Why isn’t this happening in other national blood systems with
national fractionation arrangements eg:
 France
 The Netherlands
 Spain
 Australia

8. «Humanitarian Aid»
• Identify stakeholders and INTERESTS
• Political, commercial, organisational
• Create a coalition – needs an owner
• Forge international links – EU, WHO

9. What peopl e are paying ……
….in Sri Lanka
…in Brazil

10. Prices paid in Lebano n
Product Presentation Supplier Price $US
BERIATE 1,000IU CSL Behring GmbH 575
OCTANATE 1000IU
Octapharma Pharmazeutika
Produktions GesmbH 556
FACTANE 1,000IU LFB Biomedicaments 595
HAEMATE P 1000IU CSL Behring GmbH 601
KOGENATE FS antihemophilic factor (recombinant) 1,000IU Bayer HealthCare LLC 816
NOVOEIGHT 1,000IU Novo Nordisk AS 942
NUWIQ 500IU Octapharma AB 555
RECOMBINATE 500IU Baxter SA 463
WILFACTIN 1000IU LFB Biomedicaments 1,181

11. Prices for FVIII CFCs paid by the
Australian NBA 2015-16
Factor VIII
(plasma derived -
domestic)
Biostate
250 IU
CSL Behring
(Australia) Pty Ltd
$215.12
68 US cents/IU500 IU $430.25
1000 IU $860.50
Factor VIII
(recombinant -
imported)
Advate
250 IU
Baxalta Australia
Pty Ltd
$75.00
24 US cents/IU
500 IU $150.00
1000 IU $300.00
1500 IU $450.00
2000 IU $600.00
3000 IU $900.00
https://www.blood.gov.au/pubs/1516report/part-5-appendices/appendix-3-plasma-and-recombinant-products-supplied-under-contract-2015-16.html

12. 12
F A C T O R V I I I P R I C E P E R U N I T I N T H E U N I T E D S T AT E S F R O M 1 9 8 0 T O 2 0 1 5
( R e c o m b i n a n t & P l a s m a - d e r i v e d )

13. 13
• Infusing twice weekly with rFVIIIFc at 42.7 IU/kg per dose required less clotting factor than
infusing every 56 h with rFVIII 33.75 IU/kg per dose
• Annual bleeding rates were similar.
• Base case analysis suggested that total FVIII costs were equated when rFVIIIFc cost 1.18 times
more per IU than rFVIII, assuming similar adherence.
• In 2016, average Elocate price was 15.7 % more expensive than average rVIII price (MRB)

14. Cost considerations for FIX-Fc regimens
FIX
Prescribed prophylaxis regimens
Standard factor replacement
Label prophylaxis regimens EHL factor replacement
Strategy #1
40 IU kg−1 twice
weekly
Strategy #2
67 IU kg−1 twice
weekly
Strategy #1
50 IU kg−1 once
weekly
Strategy #2 100 IU kg−1 every
10 days
Price per unit $1.06 $1.06 $2.85 $2.85
Factor cost per year per adult
patient (70 kg)
$308 672 $517 026 $518 700 $728 175
Comparative premium cost 1 ×1.7 ×2.4
Number of infusions saved per
year
Baseline – 52 67
Haemophilia (2015), 21, 285–288
•Label strategy #1 and #2 differ by 15 infusions per year
•Premium cost for #2 is $13,900 per dose saved
•Annual factor usage 2600 IU/kg for #1 vs. 3650 IU/kg for #2
•Unnecessarily high peaks, lower troughs with 10 day regimen

15. Biosimil ar s
• The rationale behind the introduction of biosimilars is to increase price
competition, an effect of which is often reduced prices.
• The increased competition resulting from biosimilars entering the market
affects not just the price of the respective biosimilars reference product, but
also the price of the whole product class.
• It can have almost as large an impact on the total market price as it has on
the biosimilar/reference product price.
«The Impact of Biosimilar Competition in Europe» Quintiles May 2017

16. To t a l c h a n g e i n p r i c e p e r T D s i n c e t h e e n t r a n c e o f b i o s i m i l a r s
f o r e a c h t h e r a p y a r e a i n t h e E u r o p e a n E c o n o m i c A r e a
16
«The Impact of Biosimilar Competition in Europe» Quintiles May 2017

17. In India………
17
According to the Economic Times, the price gap for the originator
version is INR1,200 ($17.97) with the Roche price at INR29,500 for
100mg injection, compared to INR28,300 for the Reliance version
http://www.fiercepharma.com/pharma-asia/india-s-reliance-life-sciences-brings-first-bevacizumab-biosim-to-market

18. «Biosimilar» CFCs ?
• Novoeight
• Rexubis
• Ixinity
• (Greengene)
• Coagil-VII
• Octofactor
• Innonafactor
Why are there not more
Biosimilar CFs in eg
China, India?

19. Ekaterina Shiller et al. Blood 2015;126:4703
Safety and Efficacy of Octofactor – biosimilar BDD rVIII ("GENERIUM", Russia) in Prophylactic
Treatment in Adolescent Patients with Severe and Moderate Hemophilia A

20. H e a l t h s p e n d i n g b y c o u n t r i e s a n d c u r r e n t E s s e n t i a l
M e d i c i n e s L i s t ( U S a n d S o u t h E a s t A s i a n R e g i o n o f W H O )
20

21. ATC Classification of drugs in WHO EML (2011) and
India EML ( 2011)
21
*Items that are not
included in ATC classes
(e.g., coal tar,
calamine,
cryoprecipitate, etc.)

22. Clinical trials -em be ddi ng treatment
• All clinical trials should be done according to the
principles of Good Clinical Practices (GCPs)
• These include the principles of the Declaration of Helsinki
 Including the continuation of treatment in trial subjects after the trial
completion
 Including the principle of not exposing subjects to harm
• Many clinical triasl to «prove» prophylaxis in haemophilia
are being done in the emerging countries
• By continuing treatment in the young patient population,
a number of future leaders can be saved for the
haemophilia community

23. Reflecti ons
• Much of the plasma FVIII donated globally is not going to
patients
• To address this, strategies recognising the interests and
stakeholders in blood service delivery are needed
• Nevertheless, the cost of established and some new CFCs is not
increasing in real terms
• The retreat of governments from the provision of health care is