The role of vaccine trial centers in identifying signatures of vaccine efficacy and designing next-generation vaccines

Transcription

1 The role of vaccine trial centers in identifying signatures of vaccine efficacy and designing next-generation vaccines Knowledge for Growth 26 May 2016 Hilde Revets Research& Innovation Manager - VAXINFECTIO

2 Agenda How academia (active in the clinic) can build a platform to bring concepts to the clinic, conduct clinical trials and provide solutions to patients with high unmet needs Development of new vaccines for prevention and treatment Creation of a network of expert centers for vaccination 1 Hub of dedicated vaccine trials Supportive governmental environment for vaccine trials and research

3 Agenda Development of new vaccines for prevention and treatment Creation of a network of expert centers for vaccination 1 Hub of dedicated vaccine trials Supportive governmental environment for vaccine trials and research

4 Acute myeloid leukemia Acute myeloid leukemia (AML) the facts 5-yr OS: 26.2 %? high relapse rate 75% in CR1 relapse <2yr probability CR2 only 25% Relapse prevention is a major therapeutic goal develoment of a dendritic cell vaccine (cancer vaccine) for AML Data from: NCI SEER, cohort Laboratory for Experimental Hematology Prof. Dr. Zwi Berneman

5 TRIAL SET-UP apheresis WBC CD14 CliniMACS WT1-encoding mrna electroporation MONOCYTES AML patient in remission 4x biwk bimo ID injection DENDRITIC CELLS 8 days GM-CSF + IL-4 Maturation TNF /PGE2/KLH WT1 : Wilms tumor protein

6 mrna electroporation to load DC with antigen antigen proteasome MHC I TcR CD8+ T cell DC nucleus Ag mrna Activation of Ag-specific killer Tcell Van Tendeloo et al, Blood 2001; Van Driessche et al, Leukemia 2005 & Cytotherapy 2009

7 Clinical results Conversion of partial remission into complete remission following vaccination with WT1 mrnaelectroporated dendritic cells (2/3) Van Tendeloo et al, PNAS 2010

8 Getting your ATMP to the market GOOD MANUFACTURING PRACTICE (GMP) HUMAN CLINICAL TRIALS Pre-clinical Phase I Phase II Phase III Phase IV Market Dec 2008

9 Centre for Cell Therapy and Regenerative Medicine Centrum voor Celtherapie en Regeneratieve Geneeskunde (CCRG)

10 Good Manufacturing Practice (GMP) Ground plan 'GMP clean room' materials cell products and tissue waste pass-box to Cell and tissue bank

11 Clinical CCRG DC VACCINE FOR LEUKEMIA PHASE I/II PHASE II MULTICENTRE DC VACCINE FOR MESOTHELIOMA GLIOBLASTOMA PHASE I/II DC VACCINE FOR MULTIPLE SCLEROSIS PHASE I/II DC VACCINE FOR CMV HIV PHASE I/II PHASE II LIMBAL STEM CELL GRAFTS PHASE I/II PHASE II MULTICENTRE

12 Agenda Development of new vaccines for prevention and treatment Creation of a network of expert centers for vaccination 1 Hub of dedicated vaccine trials Supportive governmental environment for vaccine trials and research

13 Three dedicated human vaccine trial centers in Flanders LUVAC (Leuven University Vaccinology Center)

14 Our common mission Contribute to the development of new vaccines and the improvement of existing vaccines for the prevention or treatment of infectious diseases Translate study results into scientific output: publications, master and Ph.D. theses Provide information on vaccines and vaccination to health care providers and the general public

15 Started in A strong consortium: some key figures CEV - UAntwerpen CEVAC - UGent LUVAC KU Leuven 1994 as CEV (first vaccine trial in 1984) (experience since 1989) FTE Studies/year (last 5 y.) vaccine Total # studies > 200 > 200 >40 Study size (min-max) # sponsors (industry) ± 10 (incl. SME) ± 8 ±7 vaccine # registered volunteers ERB lead time - Phase 1 - Phase 2-4 ± 8500 F/M: 60/40 Max. 15 days Max. 28 days ± /3 female Max. 15 days Max. 28 days ± Close interaction between the 3 centers and successful collaboration for several research projects and multi-center vaccine trials

16 Evaluated vaccines INFANTS CHILDREN DTPa (acellular pertussis) DTPa+Hib+polio+HBV Meningococcus (MenC) Measles-Mumps-Rubella + VZV Poliovirus Pandemic influenza (H1N1v 2009) ADOLESCENTS HAV HBV HSV HPV Influenza H1N1v 2009 ADULTS Hepatitis A, hepatitis B (HBV), hepatitis A/B HPV, RSV,.. Tuberculosis, malaria, HIV Seasonal influenza Pandemic influenza (H5N1, H1N1v 2009) Group B Streptococcus, Staphylococcus aureus Novel adjuvant systems ELDERLY Seasonal influenza Pandemic influenza (H1N1v 2009) Streptococcus pneumoniae Varicella zoster virus RSV SPECIAL POPULATIONS HBV (Fendrix) in hemodialysis patients

17 Recent media attention for Belgium as trial centre country De Morgen, Laatste Nieuws 9/4/2015

18 Belgium at risk of losing lead position in CT despite unique assets Lead position: Quality (cooperation with academic world)/ Expertise Short approval timing Very early access to patients Access to CT sites Hurdles: Difficulty recruiting patients Lack of transparency of CT costs Efficiency CT process (contracts, insurances, )

19 The way forward for vaccine trials: be competitive with the rest of Europe! Flanders Vaccine offers opportunities: One-stop-shop One submission for vaccine trial applications/ec Standardization of contracts, insurances, budgets and other studyrelated documents Same SOP in all vaccine trial centres Common training of staff involved Stronger branding of region/country for vaccine trials Inform and educate population of volunteers Professional recruitment and tracking systems Guaranteeing large groups of well documented volunteers

20 The way forward for vaccine trials: 3 strategic initiatives to be taken 1. Create a network of expertise centres = 1 Hub of dedicated vaccine trials centres: To be visible through websites Share best practices Improved access to volunteers more efficient recruitment 2. Supportive governmental environment for vaccine trials: In collaboration with FAGG process of consultations Build registry of volunteers 3. Standardization + centralization one-stop-shop Facilitate the processes/ submissions/ approvals/

21 Need for governmental support recognized by our Minister of Public Health Active involvement in creating CoE and one-stop-shop

22 The role of vaccine trial centers in identifying signatures of vaccine efficacy and designing next-generation vaccines Knowledge for Growth 26 May 2016 Hilde Revets Research& Innovation Manager - VAXINFECTIO