1. Accessibility of medicinal products before marketing authorisation : The French experience C. Bélorgey Division on Evaluation of medicinal products of Special Status and Clinical Trials 30 March 2007

2. 2 Accessibility of medicinal products Marketing authorisation Inclusion of patients in clinical trials Compassionate use

3. 3 1 – Facilitating inclusion in CTs: the French public clinical trials registry

4. 4 Need for transparency for CTs (1) Access to new MP through participation in CTs Protection of individual participants Reduction of unnecessary duplication of CTs Improvement of knowledge (negative results) ……….

5. 5 Need for transparency for CTs (2) All parties associated in CTs – patients – doctors – scientists International Committee of Medical Journals Editors 2005 : conditions for publication WHO : the international CTs registry platform European commission (Emea): 2 projects – Eudrapharm (CT on medicinal products with MA) – Paediatric Regulation : all CTs on children (PIP) USA : clinicaltrials.gov (serious diseases) Member states initiatives (Italy, France..)

6. 6 Regulatory provision (2004) : all authorised CTs must be registered in a publicly available registry set up by the competent authority (Afssaps) To be accessible on Afssaps website/Q4 2007 Details of the process and content are being resolved The CT description and status in France The CT results (summary) In France

7. 7 From national initiatives to an European clinical trials registry ?

8. 8 2 – Developing a strong compassionate use system: the French ATU system ( Authorisations for temporary use)

9. 9 General principles of ATU (1) Regulatory provision laid down in France in 1994 This provision allows early access to new promising drugs not covered by a MA in France (approved abroad or being developed) when there is a major public health need. With prior authorisation and control by the competent authority: Any use of a MP not holding a MA or not used within a CT is subject to prior authorisation (ATU), granted by Afssaps

10. 10 General principles of ATU (2) Criteria for ATU : treatment, prevention or diagnosis of a rare or a serious disease no satisfactory alternative method available in France efficacy and safety are presumed benefit expected for the patients authorisation for a limited period of time ATUs are not clinical trials (CTs) ATUs must not replace or slow down CTs

11. 11 2 types of ATU Nominative ATUCohort ATU on a named patient basis on the request and responsability of the physician safety and efficacy of the MP are presumed compassionate situations +++ many drugs, few patients for a group of patients applied by the company, commitment to submit a MA safety and efficacy of the MP are highly presumed SPC, patient leaflet, labelling Follow up of patients and data collection according to a protocol for therapeutic use and data collection periodic data reporting to Afssaps few drugs, many patients

12. 12 Some figures >600 MPs assessed since 1994 220 MPs subject to ATU in 2006 (57 new ones) Availability 10-12 months on average before MA Cohort ATU ≃ 108 since 1994. 10 in 2006 Nominative ATU 2006:  25 000 ATU ; 550 refusal / year  therapeutic areas : 33% 14% 17% 19% Oncology Inf. diseases CNS dis. Metabolic dis. Others

13. 13 Significant examples HIV : Zerit (D4T), Epivir (3TC), Crixivan (indinavir), Norvir (ritonavir), Invirase (saquinavir), Viracept (nelfinavir), Viramune (névirapine), Sustiva (effavirenz), Ziagen (abacavir), Fortovase (saquinavir), Rescriptor (delavirdine), Agenerase (amprénavir), adefovir, Norvir soft caps (ritonavir), Kaletra (lopinavir/ritonavir), tenofovir, atazanavir, Fuzeon, tipranavir, darunavir, TMC125, MK0518, maraviroc… Designated orphan medicinal products  About 80 MPs in ATU/422 positive opinions by COMP  Among the 35 MA or positive opinions by CHMP  24 ATU (70%) and 29 months in average before MA

14. 14 Where to find the information? www.afssaps.sante.fr The French CTs register (pending) List of cohort ATUs with SPCs List of medicinal products available by nominative ATUs (on a monthly basis)

15. Thank you! C. Bélorgey Division on Evaluation of medicinal products of Special Status and Clinical Trials March 2007