Robert Van Exan, Ph.D President: Immunization Policy & Knowledge Translation. 3/22/2016 R Van Exan: Immunization Policy & Knowledge Translation 1

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1 Robert Van Exan, Ph.D President: Immunization Policy & Knowledge Translation 3/22/206 R Van Exan: Immunization Policy & Knowledge Translation

2 Disclosure Statement Disclosure of Relationship I am a member of an Advisory Board or equivalent with a commercial organization. I am a member of a Speaker Bureau. I am an independent consultant. I have received payment from a commercial organization (including gifts or other consideration or in kind compensation). I have received a grant(s) or an honorarium from a commercial organization. I hold a patent for a product referred to in the CME/CPD program or that is marketing by a commercial organization Company/Organization Sanofi Pasteur Ltd Astellas Pharma Canada, Inc Biointillect Pty Ltd International Centre for Infectious Diseases I hold investments in a pharmaceutical organization, medical devices company or communications firms. I am currently participating in or have participated in a clinical trial within the past two years.).

3 Currently Licensed Vaccines in Canada 77 licensed Vaccines in Canada 70 marketed Vaccines in Canada Many over 50 years old Technologies relatively old 2 Manufacturers 86% from 3 manufacturers Type Vaccine Number Total Childhood Adolescent/ pre adolescent Adult/Seniors DPT Polio Hib Hep B 4 MMR and/or Vericella 6 Rotavirus 2 Pneumococcal Conjugate 3 Meningococcal 9 Boosters - Tetanus, Diphtheria, Polio 6 HPV 3 Influenza 2 Travel 3 Pneumococcal Polysaccharide 2 Zoster Rabies 2 RIG 2 Other BCG 2 77 Based on an analysis of vaccines listed in the Health Canada Drug Database 3/22/206 R Van Exan: Immunization Policy & Knowledge Translation 3

4 Currently Licensed Vaccines in Canada All but two are vaccines which prevent infectious diseases All but one have been reviewed by NACI Non Infectious Disease Vaccines: Zostavax prevents re-emergence of varicella zoster virus (i.e. prevents shingles a non-infectious disease) Immucyst BCG vaccine adapted for therapeutic use in the treatment of bladder cancer Based on an analysis of vaccines listed in the Health Canada Drug Database 3/22/206 R Van Exan: Immunization Policy & Knowledge Translation 4

5 BCG Immucyst The first vaccine to be adapted for a therapeutic application. Originated as BCG vaccine in a 40 dose package Pivotal study by Morales 976 led to the licensing and use of this product as an immunotherapeutic for the treatment of superficial bladder cancer. BCG was evaluated by NACI as a vaccine and recommendations were published in the first edition of the Guide to Immunization for Canadians in 979 but the immunotherapeutic indication was not mentioned. Immucyst was Licensed as an immunotherapeutic prior to the existence of CADTH and was never evaluated as a drug or cancer therapy. 3/22/206 R Van Exan: Immunization Policy & Knowledge Translation 5

6 New Vaccines in the pipeline Total vaccines in clinical development* = 259 Allergy 3 Cancer 05 Infectious Diseases 8 Other 23 Vaccines: Prevention vs Therapeutic Prevention = 03 Therapeutic = 56 PhRMA 206 Report on Vaccines in Development 3/22/206 R Van Exan: Immunization Policy & Knowledge Translation 6

7 LOW MEDIUM HIGH Infectious Disease Vaccine Pipeline CCMOH Ranking Infectious Disease Pipeline 2 Influenza Influenza Respiratory Syncytial virus RSV Clostridium difficile C difficile Group A streptococcus streptococcal Streptococcus pneumoniae streptococcal Hepatitis C hepatitis C Bordetella pertussis (Whooping cough) Pertussis Chlamydia trachomatis Staphylococcus aureus Staphylococcal Human immunodeficiency virus (HIV) HIV Mycobacterium tuberculosis (TB) Tuberculosis Neisseria gonorrhoeae Norovirus Norovirs Haemophilus influenzae non type b Haemophilus influenzae non typeable Herpes zoster Herpes zoster Meningococcal serogroup B meningococcal Borrelia burgdorferi (Lyme disease) Herpes simplex type 2 HSV Helicobacter pylori Pseudomonas aeruginosa Pseudomonas aeruginosa Human papillomavirus Group B streptococcus Group B streptococcus Rabies virus rabies Dengue virus Dengue Rotavirus West Nile virus West Nile virus Parvovirus B9 Cytomegalovirus (CMV) CMV 3/22/206 Vancomycin-resistant enterococcus R Van Exan: Immunization Policy & Knowledge Translation MMR DPT Polio Hib HepB E coli Pneumococcal MERS CoV chronic hepatitis B Ross River virus Shigella Equine encephalitis virus leishmaniosis tularemia Ebola Anthrax Ebola Anthrax Zika group B Streptococcal hookworm smallpox Preventive = 96 Treatment = 22 Phase = 5 Phase 2 = 46 Phase 3 = 6 PHAC Vaccine research and development priorities 2 PhRMA 206 Report on Vaccines in Development

8 LOW MEDIUM HIGH Infectious Disease Vaccine Pipeline CCMOH Ranking Infectious Disease Pipeline 2 Influenza Influenza Respiratory Syncytial virus RSV Clostridium difficile C difficile Group A streptococcus streptococcal Streptococcus pneumoniae streptococcal Hepatitis C hepatitis C Bordetella pertussis (Whooping cough) Pertussis Chlamydia trachomatis Staphylococcus aureus Staphylococcal Human immunodeficiency virus (HIV) HIV Mycobacterium tuberculosis (TB) Tuberculosis Neisseria gonorrhoeae Norovirus Norovirs Haemophilus influenzae non type b Haemophilus influenzae non typeable Herpes zoster Herpes zoster Meningococcal serogroup B meningococcal Borrelia burgdorferi (Lyme disease) Herpes simplex type 2 HSV Helicobacter pylori Pseudomonas aeruginosa Pseudomonas aeruginosa Human papillomavirus Group B streptococcus Group B streptococcus Rabies virus rabies Dengue virus Dengue Rotavirus West Nile virus West Nile virus Parvovirus B9 Cytomegalovirus (CMV) CMV 3/22/206 Vancomycin-resistant enterococcus R Van Exan: Immunization Policy & Knowledge Translation MMR DPT Polio Hib HepB E coli Pneumococcal MERS CoV chronic hepatitis B Ross River virus Shigella Equine encephalitis virus leishmaniosis tularemia Ebola Anthrax Ebola Anthrax Zika group B Streptococcal hookworm smallpox Preventive = 96 Treatment = 22 Phase = 5 Phase 2 = 46 Phase 3 = 6 PHAC Vaccine research and development priorities 2 PhRMA 206 Report on Vaccines in Development

9 Non-Infectious Disease Vaccines in the pipeline Allergy seasonal rhinitis allergic Asthma food allergy Peanut, Milk other animal, plant, insect allergies Cancer lung cancer prostate cancer breast cancer cervical cancer malignant melanoma Other Diabetes MS Alzheimer's Celiac Disease gastro-oesophageal reflux psoriasis colon cancer bladder cancer ovarian cancer renal other gout rheumatoid arthritis cocaine abuse smoking cessation ricin poisoning N=3 N=05 N=23 Preventive = 7 Treatment = 34 Phase = 56 Phase 2 = 78 Phase 3 = 2 PhRMA 206 Report on Vaccines in Development 3/22/206 R Van Exan: Immunization Policy & Knowledge Translation 9

10 Regulatory Environment Health Canada Biologics and Genetic Therapies Directorate (BGTD) Expertise in regulatory review of biologics Recognize the need for modification of the regulatory framework for Therapeutic Cancer Vaccines Future Directions. consider what immunotherapies may require a new regulatory framework 2. acquire sufficient knowledge to allow the application of science for development and decision-making 3. refine the scope and type of quality standards that would result in consistent and reliable products 4. define the scope and type of pre-clinical and clinical trials, including the most suitable statistical methodologies. Price Regulation PMPRB already handles both vaccines and therapeutic drugs. further research on cost and cost-effectiveness of newer cancer vaccines and immunotherapies are warranted as this is a rapidly growing field with many new drugs on the horizon. 2 JM Sarjeant, A. Klein, J. Wang (203) Developing Clinical Evaluation Guidance for Therapeutic Cancer Vaccines. Pan American Network on Drug Regulatory Harmonization VII, Ottawa 2 D. Geynisman, C. Chien, F. Smieliauskas, Chan Shen, Y Shih (204). Economic evaluation of therapeutic cancer vaccines and immunotherapy:a systematic review. Human Vaccines & Immunotherapeutics 0:, /22/206 R Van Exan: Immunization Policy & Knowledge Translation 0

11 Vaccine Evaluation in Canada National Advisory Committee on Immunization NACI Evaluation of vaccines in Canada since 964 Experts in the fields of pediatrics, infectious diseases, immunology, medical microbiology, internal medicine and public health. Travel vaccines reviewed by CATMAT Committee to Advise on Tropical Medicine and Travel established 990 Recommendations on travel vaccines Published guidelines one source of truth for vaccines in book format 2006 to present in electronic (evergreen) format National Immunization Strategy (2003) led to evolution of vaccine review Process. Can J Infect Dis Med Microbiol. 205 May-Jun; 26(3): /22/206 R Van Exan: Immunization Policy & Knowledge Translation

12 NIS impact on Vaccine Review Process Erikson de Wals Framework for Immunization criteria in 3 categories for evaluation of new vaccine programs NIS Report (2003) 2 established Canadian Immunization Committee F/P/T Issues Group focus on Immunization Program Planning & Harmonization NIS Review (2007) 3 - review mandates of NACI and CIC Interim two review process traditional NACI review of Science criteria CIC review of program criteria PHAC currently reviewing further evolution NACI CIC Public Health Perspective Health of the population Prevention Vaccines applied to populations Administered to the Healthy To Prevent Disease Province Analytical Framework. Burden of Disease 2. Vaccine Characteristics 3. Research Questions 4. Immunization Strategy 5. Cost Effectiveness 6. Acceptability 7. Feasibility 8. Equity 9. Ethical Considerations 0.Ability to Evaluate.Conformity to Programs 2.Legal Considerations 3.Political Considerations L Erickson, P. De Wals, L. Faranda (2005) An analytical framework for immunization programs in Canada. Vaccine 23; National Immunization Strategy - final report Interim Evaluation of the National Immunization Strategy 2

13 Pathway to Access for Traditional Infectious Disease Vaccines Traditional Vaccines Notice of Compliance Biologics and Genetic Therapies Directorate Price Regulation Patented Medicines Prices Review Board (PMPRB) National Evaluation - Guidance NACI Provincial Recommendation Provincial Agency or Vaccine Committee Public Health Branch Funding Provincial Public Health Budget Procurement Vaccine Supply Working Group (PWGSC) Distribution Provincial Public Health Wholesale Drug Chain Direct to HCP Delivery (administration) GP, Specialist, Pharmacist, Nurse, Hospital, Clinic, Pharmacy Vaccine Path What is the path for therapeutic vaccines? Therapeutic Vaccine Health of the individual Treatment Therapeutic drugs Administered to the sick To cure disease Evaluation Resources? Expertise? Criteria? Access Budget? Funding? Procurement? Distribution? Delivery? 3/22/206 R Van Exan: Immunization Policy & Knowledge Translation 3

14 CADTH Drug Evaluation CADTH originated in the early990 s CADTH is an independent, not-for-profit organization responsible for providing health care decision-makers with objective evidence to help make informed decisions about the optimal use of health technologies, including drugs, diagnostic tests, medical, dental, and surgical devices and procedures. Two Drug reimbursement bodies are: the Common Drug Review (CDR) Canadian Drug Expert Committee expertise in drug therapy formulary listing recommendations to F/P/T drug plans pan-canadian Oncology Drug Review (pcodr) 2 Expert Review Committee cancer therapy Recommendations on funding of cancer therapies to F/P/T ministries of health and cancer funding bodies Procedure for the CADTH Common Drug Review pcodr Procedures CADTH, 206 3/22/206 R Van Exan: Immunization Policy & Knowledge Translation 4

15 Processes: Where do Therapeutic Vaccines fit? What is the path for therapeutic vaccines? Therapeutic Vaccine Health of the individual Treatment Therapeutic drugs Administered to the sick To cure disease Evaluation Resources? Expertise? Criteria? Access Budget? Funding? Procurement? Distribution? Delivery? Pharmaceutical Path Pharmaceuticals 3/22/206 R Van Exan: Immunization Policy & Knowledge Translation 5 Notice of Compliance Therapeutics Product Directorate Price Regulation Patented Medicines Prices Review Board (PMPRB) National Evaluation/Recommendation CADTH Common Drug Review (CDR) Pan Canadian Oncology Drug Review (pcodr) Provincial Recommendation Provincial Formulary (Hospital Formulary) Funding Provincial Ministerial Approval Procurement Hospital, Drug Benefit, Third part reimbursement Distribution Wholesale Drug Chain Direct to Hospital Direct to HCP Delivery GP, Specialist, Pharmacist, Nurse, Hospital, Clinic, Pharmacy,

16 Processes: Where do Therapeutic Vaccines fit? Vaccines Notice of Compliance Biologics and Genetic Therapies Directorate Price Regulation Patented Medicines Prices Review Board (PMPRB) National Evaluation Recommendation PHAC NACI CIC Provincial Recommendation Provincial Agency or Vaccine Committee Public Health Branch Funding Provincial Ministerial Approval Procurement Vaccine Supply Working Group (PWGSC) Distribution Provincial Public Health Wholesale Drug Chain Direct to HCP Delivery (administration) GP, Specialist, Pharmacist, Nurse, Hospital, Clinic, Pharmacy Vaccine Path Therapeutic Vaccine Path? Pharmaceutical Path Pharmaceuticals 3/22/206 R Van Exan: Immunization Policy & Knowledge Translation 6 Notice of Compliance Therapeutics Product Directorate Price Regulation Patented Medicines Prices Review Board (PMPRB) National Evaluation/Recommendation CADTH Common Drug Review (CDR) Pan Canadian Oncology Drug Review (pcodr) Provincial Recommendation Provincial Formulary (Hospital Formulary) Funding Provincial Ministerial Approval Procurement Hospital, Drug Benefit, Third part reimbursement Distribution Wholesale Drug Chain Direct to Hospital Direct to HCP Delivery GP, Specialist, Pharmacist, Nurse, Hospital, Clinic, Pharmacy,

17 Moving Forward The vaccine pipeline is bringing forward an unprecedented number of new vaccines They have the potential to vastly improve the health status of Canadians through disease prevention and disease treatment What is the best way for Canada to manage the increasing volume and diversity of new vaccines and new vaccine technologies in the Pipeline? How can we provide the appropriate evaluation of these new technologies in an efficient manor that does not delay or impede public access? It is the objective of this presentation to stimulate a dialogue between all stakeholders (Government, Industry, Academia, Healthcare Professionals and the Public) to address some of these questions before these vaccines are on the doorstep. 3/22/206 R Van Exan: Immunization Policy & Knowledge Translation 7

18 Preventive Vaccines vs Therapeutic Drugs Preventive Treatment Population based Individual Health Heard Immunity No heard effect Duration of immunity years to decades Duration of effect hours to days Active ingredient µg antigen Active ingredient mg pharmaceutical Biological based processes Chemical based processes Combination of antigens common Combinations relatively uncommon Target population Target individuals with disease condition Low number of doses (range between once/life to annual) Duration of medication long (until the condition subsides) Cost Effective threshold $50k/QALY Cost Effective threshold - $250k/QALY for some cancer drugs 3/22/206 R Van Exan: Immunization Policy & Knowledge Translation 8

19 CADTH Drug Evaluation CDR Evaluation The CDR process reviews of drug submissions, and requests for advice issues formulary listing recommendations to all federal, provincial, and territorial (F/P/T) drug plans that participate in the CDR process Recommendations are made by the Canadian Drug Expert Committee The Canadian Drug Expert Committee is composed of individuals with expertise in drug therapy, drug evaluation, drug utilization, public members who bring a lay perspective. Criteria of evaluation clinical studies demonstrating the safety, efficacy, and effectiveness of the drug compared with alternatives therapeutic advantages and disadvantages relative to current accepted therapy cost and cost-effectiveness relative to current accepted therapy. patient group input Procedure for the CADTH Common Drug Review 204 3/22/206 R Van Exan: Immunization Policy & Knowledge Translation 9

20 CADTH Drug Evaluation pcodr Evaluation The pcodr Process evaluates clinical effectiveness, cost-effectiveness information and patient perspectives on cancer drugs provide cancer drug funding recommendations to Federal drug plans, Provincial/Territorial (P/T) Ministries of Health (excluding Quebec) and Provincial Cancer Agencies. recommendations are used by jurisdictions to guide their drug funding decisions Review Process: Clinical Guidance Panel produces Clinical Guidance Report (CGR) Economic Guidance Panel produces Economic Guidance Report (EGR) Expert Review Committee reviews CGR & EGR and produces a recommendation pcodr Procedures CADTH, 206 3/22/206 R Van Exan: Immunization Policy & Knowledge Translation 20