Why developing an orphan drugs registry?

Transcription

1 Why developing an orphan drugs registry? V. Giannuzzi, F. Bartoloni, F. Bonifazi, R. Conte, M. Felisi, L. Ruggieri, P. Baiardi, A. Ceci Gianni Benzi Pharmacological Research Foundation Operational office: Tecnopolis, S.P. Casamassima Km Valenzano (BA) Tel.: Tel./Fax: info@benzifoundation.org

2 Background Key tools to increase knowledge on rare diseases and facilitate research in the field of rare diseases: Registries and databases focused on rare diseases Registries and databases focused on drugs EuOrphan collects, catalogues, and disseminates information on drugs for rare diseases, including ODs in EU and US

3 The EuOrphan project Initially financed by the EC (eten /C 118/19) Started in 2005 Consorzio per le Valutazioni Biologiche e Farmacologiche (Italy) (Coordinator) Softeco Sismat S.p.A. (Italy) Istituto Superiore di Sanità (Italy) Fundación para la Cooperación y Salud Internacional Carlos III (Spain) Universidad de Barcelona (Spain) Karolinska Institutet (Sweden) Fondazione Italiana Leonardo Giambrone per la Guarigione dalla Thalassemia (Italy)

4 The EuOrphan website An user friendly interface Different kinds of queries The status of designated and approved The agency The therapeutic area

5 Aims To measure the coverage of the therapeutic needs of rare disease patients in Europe also in comparison with US To analyse the level of existing evidence supporting the MA Small number of patients to be recruited in CTs Small amount of resources invested Golden Standard RCT may be not feasible Often drugs are approved with an under exceptional circumstances MA or a conditional MA Alternative designs and approaches are more and more used

6 Methodology Information collected for each active substance: For designated ODs: designation date, orphan condition(s) and indication(s), sponsorship and its country For approved drugs: trade name, ATC code, approval date, approved indication, the Marketing Authorisation Holder (MAH) and its country, age specification, studies available in the MA dossier Information collected for each condition: therapeutic area, genetic nature, paediatric interest Descriptive statistics has been used to illustrate data related to products designated and/or approved in EU and US Sources of data: EMA Register of designated Orphan Medicinal Products and EPARs; EC Community Register of medicinal products; FDA Orphan Drug Designations and Approvals

7 Number of orphan designations RESULTS: Orphan designations in EU and US Overall number of orphan designations in EU and US A significant numerical disparity between US and EU in terms of orphan designations exists. This is not only due to the different year of entering into force of ODs law (1983 vs 2000), EMA Agency FDA 697 active substances ( 860 orphan designations) have received the orphan designation by the EU Agency 1427 active substances ( 1889 orphan designations) have received the orphan designation by the FDA

8 Number of orphan designations Number of orphan designations RESULTS: Orphan designations in EU and US Overall number of orphan designations in EU and US A significant numerical disparity between US and EU in terms of orphan designations exists. This is not only due to the different year of entering into force of ODs law (1983 vs 2000), but also, and above all, to the significantly higher number of designations released per year (1/1,9). 0 EMA Agency 697 active substances ( 860 orphan designations) have received the orphan designation by the EU Agency 1427 active substances ( 1889 orphan designations) have received the orphan designation by the FDA FDA FDA EMA Distribution curve (per year) of the orphan designations

9 Number of marketed drugs for rare diseases RESULTS: Approved drugs in EU and US The numerical disparity between US and EU in terms of approved orphan designations exists 100 Non-ODs 0 EMA Agency FDA ODs withdrawn O-like ODs EMA totally approved 62 ODs ( 70 orphan indications), and FDA approved 278 ODs ( 354 orphan indications) However, in EU the treatment of rare diseases includes also 6 orphan-like drugs; 79 medicinal products authorised before the OD Reg. (EC)141/2000 entered into force; 13 marketed drugs withdrawal from the ODs register.

10 RESULTS: Evidence supporting MA The majority of MAs of ODs has been granted without a phase I-III scheme The maximum level of evidence supporting the MA of ODs approved in Europe The MA of the following drugs was granted on the basis of bibliographic/retrospective data: 1. carglumic acid 2. betaine anhydrous 3. Mitotane 4. caffeine citrate 5. Hydroxycarbamide 6. Thiotepa 7. Zinc Retrospective/literature data 1 PK/PD trial 1 Efficacy/Safety non-controlled trial 1 RCT Phase I-III GCP development

11 Number of medicines RESULTS: Approved drugs in EU and US EMA FDA Bone and connettive tissue diseases Cardiovascular and respiratory diseases Dermatological diseases Endocrine diseases Gastrointestinal and hepatobiliary diseases Haematologic diseases Inborn errors of metabolism Infectious and immunitary system diseases Neurological and psychotic diseases Oncologic diseases Ophthalmic diseases Poisoning / overdose Renal, urinary and reproductive disease Others Distribution of approved drugs by disease area The oncologic area is the most represented. In EU no drug is marketed for Ophthalmic diseases, Poisoning / Overdose, Renal, urinary and reproductive diseases Only 60 medicines are approved with the same (or similar) indication in EU and US

12 N. of paediatric approved indications RESULTS: Drugs available for children Paediatric conditions yes no Drugs without a paediatric indication but disease affects children Drugs with a paediatric indication /1179 orphan conditions affect the paediatric population Paediatric drugs are still underestimated: about half (52,5% from EMA and 49.3% from FDA) of marketed drugs indicated for a disease affecting children, does not have a paediatric indication 0 EMA FDA In EU 46 medicines (orphan and not) has not paediatric indication, but the rare disease affects children

13 Number of approved indication by age RESULTS: Drugs available for children 200 EMA 150 FDA Very few drugs are available for the very young children

14 Conclusions Registries focused on drugs result relevant in the rare diseases field EuOrphan provides referenced scientific and regulatory data on drugs marketed or in development both in EU and US, providing a global measure of covered/uncovered patient needs In EU patients have still access to a lower number of drugs than in US difference reduced, considering non-ods marketed in EU A great part of paediatric rare diseases has still an unmet therapeutic need More efforts seem necessary to advance the availability of medicines by merging efforts at EMA and FDA level to identify innovative regulatory solutions for acquiring evidences from trials and other research sources OD registries including data we presented could be of help in focusing these efforts in the right way

15 Thank you Gianni Benzi Pharmacological Research Foundation Operational office: Tecnopolis, S.P. Casamassima Km Valenzano (BA) Tel.: Tel./Fax: info@benzifoundation.org