Treatment of childrenwith rare metabolic diseases in Poland

benefits of centralized system

Jolanta Sykut-Cegielska, MD, PhD, Ass Prof

Department of Metabolic Diseases,

Children’s Memorial Health Institute

Rare diseases are a real health care issue

• In the EU the no of people with rare diseases is ≈35 million

• There are 6000-8000 different rare disorders (www.orpha.net)

• 80% of rare diseases are genetic

• 50% of the patients die in the childhood

Rare (orphan) disease = less than 5 in 10,000 people

Represent some of the rarest, but mostlife-threatening unmet medical needs

Disease with a specific enzyme deficiency arising from single or multiple

gene defects, leading to a block ina metabolic pathway and overt clinical

signs and symptoms

IEMs classification

• Disorders of metabolic intoxication (intermediate metabolism, leading to progressive accumulation of toxic products proximal

to the metabolic block)

• Disorders of energy metabolism

• Disorders of complex molecules(synthesis, breakdown or transport)

„… in inborn errors of metabolism treatment should be implied rather as removal or even prevention of the effects of genetic defect through mitigation or elimination of clinical symptoms…”

Physician’s guide to the treatment and follow-up of metabolic diseases Nenad Blau, Georg Hoffmann, James Leonard, Joe Clark, eds. 2006, Springer

IEMs classification & treatment

• Disorders of metabolic intoxication

• Disorders of energy metabolism

• Disorders of complex molecules

• Detoxification by extracorporal exchange and drugs, special diets and products (FSMP)…

• Symptomatic / supportive

• Enzyme replacement therapy, substrate reduction therapy, BMT, HSCT…

Advanced therapiesbased on genes and cells, tissue engineering…

IEMs orphan drug orphan drug research → development → access

Translation research into development

orphan designation → marketing approval

basic research → clinical research → clinical practice

immunology11%

oncology36%

cardiovascular and respiratory

9%

antiinfectious5%

other21%

musculoskeletal and nervous

system7%

metabolism11%

In 2000 y. the EU Regulation on Orphan Medicinal Products came into force, stimulating the development of orphan drugs

Distribution of orphan designation by therapeutic class [COMP report]

Proportion of marketing approval by FDA for IEM drugs was significantly higher than that for non-IEM orphan products.

The most designations and approvals for LSD (43 and 9, respectively during 25 yrs)

[Sonali et al Pediatrics 2011]

Therapeutical health program

2008 2009 2010 2011 (JAN-JUL)

Patients no

Payments (in Euros)

Patients no

Payments (in Euros)

Patients no

Payments (in Euros)

Patients no

Payments (in Euros)

Gaucher disease therapy 56 4 409 037 61 6 239 516 64 6 099 344 57 7 015 312

MPS type I therapy 16 988 931 19 1 951 787 18 2 937 634 17 1 857 436

MPS type II therapy 0 - 18 1 752 575 37 10 067 634 35 7 305 156

MPS type VI therapy 0 - 3 659 802 4 6 806 612 3 981 413

Pompe disease therapy 0

- 19 1 515 708 18 3 160 170 19 1 952 114

Total 72 5 397 968 120 12 119 388 141 29 071 394 131 19 111 431

Source: NFZ BO6,5 (07.09.2011)

Public resources for treatment of IEMs in Poland

• Qualification to at least the most expensive therapies, is now based on clear rules (created by MoH and NHF).

• Since 2009 y. Coordinating Team (called up by NHF) has been responsible for either qualification or verification of treatment in IEMs.

Coordinating Teamfor Ultrarare Diseases

• 15 meetings

• since 08June2009 to 20June2011

• 503 applications were considered

442 - qualified for financing

18 - excluded from therapy

11 - not fulfiled inclusion criteria

19 - applications to be completed

10 - charity therapy

3 - no patient’s consent

LSD are an IEM success story (with regard to development of new therapies), but such success elswhere is needed,

e.g. a notable absence of marketing approval for any designated products for mitochondrial diseases (in USA 7 designations and 0 approvals).

[FDA data,

2011]

FSMP and orphan drugs accessin Poland

Availability ≠ access

• No temporary approval

• By compassionate use procedures

• Off-label use as a decision of regulations of „treatment experiment”, after unsuccesful application of standard treatment methods

Benefits of centralized system• Dept Metabolic Diseases in CMHI – reference center

for IEMs for Poland (by reputation)• Network of Polish metabolic centers• Selective screening program for IEMs – early detection

of metabolic patients• Polish Metabolic Group in the Polish Paediatric Society

since 2001• 4th Eastern European Metabolic Academy 2011• Educational courses for affected families (cooperation

with patient associations)• Participation in multinational clinical trials• Partnership in international networks

General objective

To promote health for children, adolescents and adults with rare organic acidurias (OADs) and urea cycle defects (UCDs) in Europe.

Specific objectives

1. European patient registry: to describe the natural history, epidemiology, current diagnostic and therapeutic strategies, to provide information to national and EU healthcare authorities

improving knowledge; evaluating current strategies

2. European evidence-based consensus care protocols provided via a website in official EU languages

providing structured information for patients, parents and healthcare professionals, improving care, providing a template

for national diagnostic and therapeutic guidelinesand patient brochures

Birmingham

LondonRotterdam

Warsaw

PortoBarcelona

PaduaZagreb

Copenhagen

ManchesterAmsterdam (AMC)

DüsseldorfMilupa

SHSPrague

Munich (LMU)

Lisbon

Zürich

Istanbul

Rome

Bruxelles

Lille

WP leader

Innsbruck

Heidelberg

Thessaloniki

Paris

Bern

Madrid

Valencia

75% coverage of the EU population

• Currently: 3 continents

19 countries

46 partners

13 associate

33 collaborating• OEA as a partner

specific training courses:

e-learning on NH3

9th European Metabolic Course (Warsaw, 25-29.09.2012)

How to improve IEMs treatmentin Poland?

• Harmonization and coordination of all activities• Through establishing national reference centres

and centres of expertise for IEMs with mission of integrated and coordinated professional care, research and education/training

• Specific framework of health care for metabolic patients

national plan for rare diseases(according to EU Council Recommendation 5June2009)

Thank you for your attention!

RDD 2011, Warsaw