Transcript Criteria for Orphan designation

The role of EMEA
in
Orphan Drug
Development
Thomas Lönngren, EMEA
Stockholm, 15 February 2005
The European Medicines Agency
• EMEA is the European Union body responsible for the
evaluation and supervision of medicines in Europe.
• Its main responsibility is the protection and promotion of
public and animal health.
• The EMEA works as a network, bringing together the
scientific resources of the Member States.
• The Agency cooperates closely with international
partners on a wide range of regulatory issues (e.g. ICH,
WHO, FDA, etc)
• The Agency was created in 1995 and is headquartered
in London.
15 Feb 2005 – Thomas Lönngren
Slide: 2
European Medicines Agency
www.emea.eu.int
Drug Therapy in Rare Diseases
Persons suffering from rare diseases
have the same rights as their fellow
citizens to safe and effective therapies
15 Feb 2005 – Thomas Lönngren
Slide: 3
European Medicines Agency
www.emea.eu.int
Orphan Regulations
• Regulation (EC) No 141/2000 of the
European Parliament and of the Council
on Orphan Medicinal Products of 16
December 1999
• Commission Regulation (EC) No 847/2000
of 27 April 2000
15 Feb 2005 – Thomas Lönngren
Slide: 4
European Medicines Agency
www.emea.eu.int
What is an Orphan Medicinal Product
Orphan Medicinal Products
• for rare diseases (affecting less than 5 in
10,000 persons)
• development costs > expected return on
investment
• life-threatening or very serious
Lack of sponsors developing orphan
medicinal products
15 Feb 2005 – Thomas Lönngren
Slide: 5
European Medicines Agency
www.emea.eu.int
What are the EU incentives ?
Market Exclusivity
Protocol Assistance
for 10 years after grant of
Centralised Procedure
EU marketing authorisation
direct access to EMEA
centralised procedure for
marketing authorisation
free scientific advice
to optimise development
EU-Funded Research
Fee Reductions
grants from Community
& Member State programmes
reduction of centralised
regulatory fees via a special fund
from EU budgetary authority
15 Feb 2005 – Thomas Lönngren
Slide: 6
European Medicines Agency
www.emea.eu.int
Application for Orphan Designation
Application should demonstrate orphan criteria
have been met:
• life-threatening or debilitating nature of condition
• medical plausibility
• prevalence < 5 in 10,000 or unlikely to generate
sufficient return on investment
• no satisfactory methods exist or medicinal
product will be of significant benefit
All claims should be substantiated by references
15 Feb 2005 – Thomas Lönngren
Slide: 7
European Medicines Agency
www.emea.eu.int
Committee for Orphan Medicinal
Products (COMP)
EMEA Committee: 31 members + Chairman
• 1 Member per Member State
• 3 representatives from patients groups
• 3 members proposed by the EMEA
COMP responsible for:
• opinions on designation
• advising on general EU policies
• international co-operation
15 Feb 2005 – Thomas Lönngren
Slide: 8
European Medicines Agency
www.emea.eu.int
Procedure for Orphan Designation
Presubmission
Validation
Evaluation
Opinion
Day 1
15 Feb 2005 – Thomas Lönngren
Slide: 9
DecisionMaking
Day 90
European Medicines Agency
www.emea.eu.int
Designation
+ 30 days
Status of Orphan Applications
120
submitted
100
80
positive opinions
60
negative opinions
40
withdrawals
20
Commission
decisions
0
2000
2001
2002
2003
2004
Up to January 2005
15 Feb 2005 – Thomas Lönngren
Slide: 10
European Medicines Agency
www.emea.eu.int
Distribution of opinions
immunology
11%
other
21%
musculoskeletal and
nervous system
7%
metabolism
11%
antiinfectious
5%
oncology
36%
cardiovascular and
respiratory
9%
immunology
cardiovascular and respiratory
metabolism
other
oncology
antiinfectious
musculoskeletal and nervous system
Up to December 2004
15 Feb 2005 – Thomas Lönngren
Slide: 11
European Medicines Agency
www.emea.eu.int
Opinions designated based on
significant benefit
• Up to January 2005: 182 out of 262 opinions
(69%) based on assumption of significant benefit
over authorised treatments in the orphan
condition
• Significant benefit to be reviewed at the time of
Marketing Authorisation to maintain orphan
status
15 Feb 2005 – Thomas Lönngren
Slide: 12
European Medicines Agency
www.emea.eu.int
Protocol Assistance
Article 6 of Regulation (EC) No 141/2000
• Protocol Assistance = Scientific Advice for
companies developing Orphan Medicinal
Products
• Revised procedure adopted by the CHMP 2003
• Implementation of changes from new
Pharmaceutical Regulation by end 2005
15 Feb 2005 – Thomas Lönngren
Slide: 13
European Medicines Agency
www.emea.eu.int
Protocol Assistance – Key Features
• Systematic pre-submission meeting with the
EMEA
• Oral explanations in the majority of cases
• Additional and specific expertise to participate in
SAWP
• Involvement of 2 representatives of the
Committee for Orphan Medicinal Products in
SAWP (Significant Benefit issues)
• Fee reduction (currently 100% = free)
15 Feb 2005 – Thomas Lönngren
Slide: 14
European Medicines Agency
www.emea.eu.int
Scientific Advice / Protocol Assistance
Procedures
100
22
32
13
50
65
75
77
0
2002
15 Feb 2005 – Thomas Lönngren
Slide: 15
2003
European Medicines Agency
www.emea.eu.int
2004
Orphan Medicinal Products
Application for Marketing Authorisation (MAA)
At the stage of MAA:
• Filing can currently be through Mutual
Recognition Procedure or Centralised Procedure
• To obtain Market Exclusivity MA must be granted
by all Member States in Mutual Recognition
• In November 2005, Centralised filing obligatory
• Fee reductions are granted by some MS’s and
by EMEA for centralised applications
15 Feb 2005 – Thomas Lönngren
Slide: 16
European Medicines Agency
www.emea.eu.int
Status of Orphan Marketing
Authorisation Applications
18 authorisations granted to date
•
•
•
•
•
•
•
•
Fabrazyme for Fabry disease
Replagal for Fabry disease
Glivec for chronic myeloid leukaemia
Tracleer for pulmonary arterial hypertension
Trisenox for acute promyelocytic leukaemia
Somavert for acromegaly
Zavesca for Gaucher disease
Carbaglu for hyperammonaemia
15 Feb 2005 – Thomas Lönngren
Slide: 17
European Medicines Agency
www.emea.eu.int
Status of Orphan Marketing
Authorisation Applications cont’d
• Aldurazyme for Mucopolysaccharidosis
• Busilvex for haematopoietic progenitor cell
transplantation
• Ventavis for pulmonary arterial hypertension
• Onsenal for Familial Adenomatous Polyposis
• Litak for Hairy cell leukaemia
• Lysodren for adrenal cortical carcinoma
• Pedea for Patent Ductus Arteriosus
• Photobarr for Barret’s oesophagus
• Wilzin for Wilson's disease
• Xagrid for Thrombocythaemia
15 Feb 2005 – Thomas Lönngren
Slide: 18
European Medicines Agency
www.emea.eu.int
Status of Orphan Marketing
Authorisation Applications cont’d
Two CHMP Opinions in decision-making
• Orfadin for Hereditary tyrosinemia type 1
• Prialt for chronic pain
Three extensions of indication
• Glivec for Gastrointestinal Stromal Tumours
• Glivec for first line use in Chronic Myeloid Leukaemia
• Glivec for paediatric use in Chronic Myeloid Leukaemia
Nine centralised applications in review process
Four applications filed through Mutual Recognition
15 Feb 2005 – Thomas Lönngren
Slide: 19
European Medicines Agency
www.emea.eu.int
Overview of “evidence”
in authorised products
• Data provided
– in 28% of products phase III studies (double
blind, randomised, placebo controlled)
– in 44% of products phase II studies
• 61% of Marketing Authorisations granted under
“exceptional circumstances”
15 Feb 2005 – Thomas Lönngren
Slide: 20
European Medicines Agency
www.emea.eu.int
Orphan Marketing Authorisations
830,000 patients
240
designated
45
marketing
applic’ns
15 Feb 2005 – Thomas Lönngren
Slide: 21
19
authorised
European Medicines Agency
www.emea.eu.int