Radek Kaczmarek - EHC

Access to new therapies:
opportunities, challenges and
barriers
The Patient Perspective
Radoslaw Kaczmarek
EHC Steering Committee
EHC Round Table, June 2013

Fervent research
• Modification of clotting factors to prolong
half-life
• Alternative strategies to enhance
haemostasis:
− targeting inhibitors of coagulation (TFPI,
antithrombin)
− replacing the missing clotting factor with a
structural mimic (bispecific antibody
mimicking FVIII)

Fervent research (2)
Kitazawa T., et al. Nat Med. 18, 1570-1574, 2012

Fervent research (3)
• General approaches to prolong half-life:
- PEGylation
- Generation of fusion proteins
- Site-specific mutagenesis to modify amino
acid sequence

Remaining potential
• Some unexplored areas remain
− engineered FIX variants may activate FX in
absence of FVIII
Milanov P., et al. Blood. 119, 602-611, 2012

Remaining potential (2)
− LDL receptor (LDLR) and LRP (LDLR-related
protein) are involved in clearance of FVIII
(potential for blocking strategies)
Kurasawa J. H., et al. J Biol Chem. 2013

New Era
• Successful development of numerous
innovative products means the largest
breakthrough since the invention of clotting
factor concentrates
− CFCs meant freedom for PwH (easy home
treatment, freedom of travelling)
− Longer-acting products will allow fewer
infusions (further reduction of time devoted to
treatment, stronger sense of independence)

Impact of new products
• Dramatic change in quality of life in a
number of ways:
− improved management of bleeds (most
bleeds effectively treated with one infusion)
− higher trough levels and thus e.g. more
effective physiotherapy

Impact of new products (2)
• Longer-acting FVIII vs FIX
− less pronounced effect in the case of FVIII
but still significant

Impact of new products (3)
• New products may rapidly improve
haemophilia care in countries that have been
lagging behind
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Facts about Poland
• Population: over 38 million people
• 4,277 patients with bleeding disorders (2,605
with haemophilia A or B)

Facts about Poland
• A former Eastern Bloc country
• Despite a vast improvement, amount and
choice of products are still limited
Before 1989

Replacement therapy in Poland
• Recombinant CFCs only for PUPs (rarely for
other patients groups)
• Bulk amount of purchased products plasmaderived
• No choice for patients
• Cost an issue
• Cost the major (if not the sole) criterion in
tenders

Replacement therapy in Poland (2)
• Primary prophylaxis for children (since 2008)
• Limited secondary/short term prophylaxis
• Majority of adults and many adolescents
with some degree of joint damage

Noone et al. Haemophilia. 19, 44-50, 2013
Opportunities for adult PwH
• Adult PwH may tremendously benefit from
prophylaxis

Opportunities for adult PwH (2)
• Limited secondary prophylaxis = reserved
attitude towards physiotherapy
• Physiotherapy key element of
comprehensive care
• Even more so in the case of PwH with
haemophilic arthropathy

Forsyth A. L., et al. Haemophilia. 17, e870-6, 2011
Opportunities for adult PwH (3)
• Benefits of physical activity in haemophilic
arthropathy:
− reduces chronic pain and disability
− reduces the risk of osteoporosis (resistance
training)
− improves balance and proprioception thus
reducing the risk of falls
‘‘It takes a child 1 year to acquire independent movement and 10
years to acquire independent mobility. An old person can lose
both in a day.’’

Speaker’s experience
• Taking part in clinical trial of longer-acting FVIII
(half-life prolonged to 19 hours)
• Resumed resistance exercises routine after a 3-
year break
• Twice per week prophylactic infusions allow
effective prevention of bleeds and sustained
improvement of lean body mass and strength
• Able to fit the training program into the daily
schedule instead of tailoring everything else to
afford exercises

Economic issues
• European pursuit of austerity still a reality
• True also in Poland
• Governments have less interest in funding
expensive therapies
• Novel therapies require strong cases and
need to be cost-effective (likely to undergo
scrutinized HTA)

Concluding remarks
• Haemophilia community on the verge of
new era of haemophilia care
• Novel products will dramatically change
many aspects of haemophilia management
and patients’ quality of life
• Potential to reshape the pricing trends of
currently available haemophilia products

Concluding remarks (2)
• Companies need to carefully consider the
economic trends when setting the launch
prices
• New products must offer a clear costeffectiveness
to pass HTAs
• Licensing bodies need to make the best
efforts to ensure a timely approval of new
products

Thank you for your attention!