1. ELPA Symposium Compassionate Use in Hepatitis C Saving lives of patients who cannot wait Thomas Berg Section of Hepatology Clinic for Gastroenterology and Rheumatology Department of Internal Medicine University Clinic Leipzig Liver- and Study Center Checkpoint, Berlin

2. Compassionate use in hepatitis C The patient who cannot wait

3. Compassionate use in hepatitis C The patient who cannot wait Effective anti- viral regimen

4. Compassionate use in hepatitis C The patient who cannot wait Effective anti- viral regimen Safety profile

5. Compassionate use in hepatitis C The patient who cannot wait Effective anti- viral regimen Safety profile Specialists

6. Compassionate use in hepatitis C The patient who cannot wait Effective anti- viral regimen Safety profile Specialists Monitoring safety and efficacy

7. Compassionate use in hepatitis C The patient who cannot wait Effective anti- viral regimen Safety profile Specialists Monitoring safety and efficacy Review Board

8. Compassionate use in hepatitis C The patient who cannot wait Effective anti- viral regimen Safety profile Specialists Monitoring safety and efficacy Review Board Legislation (country specific), Regular agencies (EMA)

9. Compassionate use in hepatitis C The patient who cannot wait Effective anti- viral regimen Safety profile Specialists Monitoring safety and efficacy Review Board Legislation (country specific), Regular agencies (EMA) Pharmaceutical Industry

10. Who cannot wait? Definitions All potential treatment options exploited? – Off-label use – Access to ongoing clinical trials – Collaboration and advice from patient oragnisations Intolerant to current therapies? Compassionate use restricted to a limited number of patients

11. Effective antiviral regimen Definitions At least Phase II studies completed – Showing clear advantage over current licensed regimens Regimen for Phase III established Efficacy data for patient populations considered for compassionate use (at least preliminary)

12. Safety profile Definitions At least Phase II studies completed – Showing no significant toxicity – Low likelihood for adverse reactions (low risk benefit ratio) Safety data for patient populations considered for compassionate use (at least preliminary) Drug-Drug interaction studies Co-morbidities have to be considered

13. Concerns Patients who cannot wait are normally not part of phase II and III trials

14. Solution? Patients who cannot wait are normally not part of phase II and III trials Targeting special populations with increased morbidity and mortality risk early during drug development programs

15. Safety Concerns Toxicities associated with the use of DAAs in viral hepatitis – Fialuridine in HBV (Death due to mitochondrial tox.) – Cyclophilin Inhibitor (Death due to pancreatits) – Polymearse Inhibitor (Death due to infection /lymphopenia) Early access programme for Triple therapy – Mortality rate: 2%

16. Safety Concerns Uncontrolled use Rare side effects in special population Pontential drug-drug interactions Physicians may not be well trained to the new drugs Improper use may lead to resistance development – Negatively impact future treatment options

17. The specialist Definitions? Long-term experience in managing the corresponding patient population Experience with the „new“ regimens Study investigator Working in a specialized center (emergency ward, ICU, cardiologists, nephrologists,….)

18. Monitoring, Reviewboard Protocol Definition of patient population Inclusion and exclusion criteria How to Monitor Data reporting

19. Conclusions New drugs with favourable risk benefit profile Defintion of patients with the most urgent need Collect data and experience of treatment in these patients (safety, DDI, draft a document) Position of patients, industry, physicians, EMA If everything looks safe, consider the programme And…. at the end we have to comply with the country specific legal rules