Overcoming Barriers in Vaccine Development and Translation: Highlighting Innovative Practices

Transcription

1 ACO Annual CHVI R&D Alliance Meeting 2014 Overcoming Barriers in Vaccine Development and Translation: Highlighting Innovative Practices Executive Summary Thursday, May 1, 2014, St. John s, Newfoundland Ancillary Session by the Canadian HIV Vaccine Initiative (CHVI) Research and Development Alliance Coordinating Office (ACO) The 23 rd Annual Canadian Conference on HIV/AIDS Research CAHR 2014 Prepared by Renée Barclay, Communications Specialist Contact Alliance Coordinating Office T: (204) E: Website: alliance-aco.ca

2 1. Executive Summary Twelve national and international experts in vaccine discovery and development delivered presentations and exchanged information from the perspectives of basic science, regulatory affairs and industry at the Canadian HIV Vaccine Initiative (CHVI) Research and Development Alliance Coordinating Office (ACO) Annual Meeting held in St. John s, Newfoundland on May 1, This full-day meeting was an ancillary session to the 23 rd Annual Canadian Conference on HIV/AIDS Research (CAHR 2014). The meeting provided updated information about barriers to HIV vaccine development and highlighted innovative steps to overcome them. World-renowned experts provided perspectives from research, regulatory affairs, pharma and international organizations (see Appendix 1). Topics of discussion included advances in the field of HIV vaccines as well as other vaccines that may have relevance to progress against difficult disease targets. There were opportunities for dialogue and discussion during panel sessions and through informal networking opportunities. The specific objectives of the ACO Annual CHVI R&D Alliance Annual Meeting were: To provide updated information about barriers to HIV vaccine development and how steps are being taken to overcome them. To share information about innovation in developing vaccines other than HIV, that may have relevance to HIV vaccine development. To increase collaboration in the development of HIV vaccines and vaccines other than HIV. More than 60 people from various disciplines attended the full-day event. The panel of presenters included a robust Canadian contingent, including Dr. Marc Ouellette of the Canadian Institutes of Health Research (CIHR), Dr. Dean Smith of Health Canada, Stacey Nunes of the National Research Council of Canada (NRC) and Dr. Joanne Langley of Dalhousie University. Dr. Catherine Hankins of the Amsterdam Institute for Global Health and Development, Dr. Rosanna Peeling of the London School of Tropical Medicine and Hygiene, Dr. Bartholomew Dicky Akanmori of the World Health Organization (WHO), and Dr. Tom Hassell of the International AIDS Vaccine Initiative (IAVI) were among the international speakers. Industry representatives included Dr. Tony D Amore from Sanofi Pasteur, Dr. James Mansi from Novartis Pharmaceuticals Canada, Dr. Nathalie Charland from Medicago Inc., and Dr. Marianne Stanford from Immunovaccine Inc. Discussion focused on the continued need for an effective HIV vaccine which has eluded scientists since acquired immune deficiency syndrome (AIDS) was first reported over 30 years ago. It was noted that the HIV vaccine discovery and development process is highly complex, and while scientific progress has been made, partnerships and collaborations at national and international levels are needed. The meeting was organized into three themes Optimizing Efforts in HIV Vaccine Development and Clinical Trials; Optimizing Regulatory Practices; and Perspectives from Pharma and International Organizations on Overcoming Barriers for HIV Vaccine Development. Each theme included presentations and panel discussions outlining the challenges, innovations and future considerations for that particular area. 2

3 1.1 Optimizing Efforts in HIV Vaccine Development and Clinical Trials This theme focused on the increasingly important role that non-vaccine HIV prevention plays on vaccine discovery, and how unique networks in Canada are augmenting clinical trials and research capacity. Current and future non-vaccine prevention strategies against HIV infections will influence the design and implementation of future HIV vaccine clinical trials. Combination HIV prevention takes into account the biomedical, behavioural, and structural elements to address immediate risks, underlying vulnerabilities and the pathways that link them. Combination HIV prevention has gained ground as a conceptual framework for prevention. Moving forward, HIV vaccine trials must factor in the scale-up of prevention strategies such as antiretroviral treatment (ART), pre-exposure prophylaxis (PrEP), and voluntary medical male circumcision (VMMC). The discussion at the ACO Annual CHVI R&D Alliance meeting identified some possibilities for Canadian involvement in overcoming barriers to HIV vaccine development. Some of the key points raised during the meeting included: Current and future non-vaccine prevention strategies against HIV infections will influence the design and implementation of future HIV vaccine clinical trials. Canada has unique networks and expertise with clinical trials and research capacity. Regulatory harmonization/convergence and capacity building are essential for future clinical trials in developing countries. Building local and regional regulatory capacity is important for HIV vaccine clinical trials in Africa. International partnerships and standardization can facilitate improvements in regulation of diagnostic products and vaccines. Innovative manufacturing technologies used for other vaccines offer many advantages and may have relevance to HIV vaccines. Collaboration and partnerships are keys for HIV vaccine development. Vaccine innovation also requires complex knowledge with diverse, multidisciplinary partnerships involving more than one country. Different funding strategies are necessary, and the CIHR is helping to meet the need by supporting HIV research in the areas of community-based research, advancing basic science, and prevention of mother-to-child transmission. It provides funding for Canadian-based research to advance basic science through fellowships and new investigator awards, catalyst grants, operating grants, emerging team grants, Canada-LMIC (low- and middleincome countries) team grants, and mucosal immunology team grants. Meanwhile, the NRC facilitates innovation by assisting both research investigators and companies. Working with smalland medium-sized enterprises (SMEs), the NRC supports the vaccine sector by offering expertise, unique Canadian facilities and platform technologies, including level 2 and 3 containment facilities for animal resources and biologics production. Barriers to HIV vaccine development in Canada include: The risks associated with delivering candidate vaccines and phase 1 adjuvant technologies to healthy patients, The high cost of biomanufacturing, and The need for delivery to numerous people to achieve herd immunity. 3

4 Overcoming these challenges might involve increased collaboration an area of strength in Canada. The nation already has unique, extensive networks and expertise with clinical trials and research capacity, whereby Canadian vaccine researchers collaborate across provinces and institutions. Cross-border collaborations also extend internationally and there is good capacity in Canada to build partnerships to prevent infectious diseases through vaccine research. Such collaboration, across multiple disciplines will be necessary to find innovative solutions in HIV vaccine development in Canada. 1.2 Optimizing Regulatory Practices The second theme of the day highlighted harmonization of international regulatory practices. All of the presentations addressed ways to optimize existing regulatory practices and facilitate similar processes in countries without such regulation. An ongoing issue in African countries is the urgent need for affordable and accessible diagnostics to determine whether or not people require HIV treatment. International collaborations and partnerships can facilitate improved regulation of diagnostic products and vaccines. Inter-regional regulatory harmonization activities pertaining to diagnostics have been ongoing since 2011 to facilitate the regulatory process. As clinical trials are becoming more complex, there has been a shift away from traditional models in HIV vaccine research to more complex platforms that use numerous designs. Such innovation and early-phase trials are positive advances; however the rush to start trials early presents legal and regulatory hurdles. Expanded communication, collaboration and support for regulators of resourcelimited countries from those of developed countries are necessary. Increased regulatory harmonization through regional economic communities (RECs) is addressing those challenges to some degree, but more is needed. Health Canada s earlier regulatory mentoring work in coordination with the WHO for India, has led to a CHVI multi-year effort in cooperation with the Bill & Melinda Gates Foundation (BMGF) and the WHO with African regulators to support HIV clinical trials. HC also works directly with WHO and the African Vaccine Regulatory Forum (AVAREF) to further CHVI objectives. Examples of CHVI regulatory capacity building activities include the following: International regulatory forums/events: HC hosts a number of regulatory vaccine/clinical trial events and sponsors the participation of applicable national regulatory authorizes (NRAs) (e.g., Health Canada International Regulatory Forum in Ottawa) Participation in international regulatory networks: HC participates in the AVAREF, Developing Countries Vaccine Regulators Network (DCVRN), and the International Conference of Drug Regulatory Authorities (ICDRA) Training / mentoring programs: HC provides NRA to NRA review mentoring in the area of vaccine and clinical trial regulation for selected countries through the CHVI Regulatory Capacity Mentorship Program. In addition, Health Canada offers vaccine and clinical trialsrelated courses in collaboration with WHO to a wider range of countries (e.g., WHO sponsored pre-qualification workshops). 4

5 1.3 Perspectives from Pharma and International Organizations on Overcoming Barriers for HIV Vaccine Development Five presenters offered interesting and diverse perspectives for this theme which emphasized the importance of collaboration and partnerships, as well as how innovative technologies used for other vaccines may be applicable to HIV vaccine research and development. Traditional methods of preparing vaccines have so far been unsuccessful with HIV, therefore new approaches and innovative thinking are needed to progress research and development. Such innovation may require looking outside of traditional models and seeking help from outside the HIV field. IAVI conducts policy analysis and serves as an advocate for the AIDS vaccine field. The organization helps coordinate financing and research collaborations. Vaccine discovery will hinge on active collaboration at the scientific, technical and management levels. Meanwhile, innovative research, such as the development of Immunovaccine Inc. s cancer vaccines, may have relevance to other infectious disease models. The company s product, DepoVax, has excelled in cancer immunotherapy, and may have several parallels with HIV vaccines. In particular, the role of checkpoint inhibitors is something HIV might derive from the cancer field. Plant-based technologies also offer many advantages to vaccine development that may pertain to HIV vaccines. Medicago Inc. develops virus-like particle (VLP) vaccines using a transient expression system which produces recombinant vaccine antigens in plants. The technology could produce more potent vaccines in a relatively quick and cost-effective manner. Plant-based vaccines and therapeutic proteins are a multi-faceted technology used for multiple products such as vaccines against severe acute respiratory syndrome (SARS), rabies, and others. In addition, novel technologies such as recombinant deoxyribonucleic acid (DNA) and reverse vaccinology have greatly improved the efficacy of the vaccine-target identification selection and development process. Novartis Vaccines uses many new technologies to produce products that fight several vaccine-preventable viral and bacterial diseases, including meningococcus B. Building on the successes of vaccines developed in the past 30 years, new products will be designed to address infectious diseases once thought to be impossible to prevent. Despites these research advances, there remains a high risk associated with vaccine development, which places pressure on the cost of developing vaccines. The length of time it takes to develop most vaccines (eight to 12 years) and relatively low success rates (10% to 15%) are other deterrents. Key issues around pricing, capacity, and distribution have traditionally been resolved in the developed world first. However, with a new paradigm, developing countries would be at the front of the queue instead of the back of the line. This would require not only accommodations from industry, but also financing and capacity building from other partners. Guarantees of purchase, regulatory harmonization, tax credits and other incentives for industry to manufacture vaccines for developing countries need to be in place. It could include new regional plants that are either owned by industry, the public sector, or through joint ventures. 1.4 Special Guest Speaker Dr. José Esparza was scheduled to deliver a presentation at the conclusion of the panel discussions, however he was unable to attend the meeting due to travel issues. In his place, Dr. Hammond provided a brief overview of Dr. Esparza s recent scholarly paper, What Has 30 Years of HIV Vaccine 5

6 Research Taught Us? containing similar key points. 1 He explained that accelerating HIV vaccine development will require out-of-the-box thinking, with a shift in paradigms to existing vaccine research and development models. He outlined six recommendations to accelerate the development of an HIV vaccine: Innovative research with protected funding to explore out-of-the-paradigm approaches (perhaps not less than 10% of the total investment); Basic research, exploring novel opportunities to conduct translational research, including the implementation of small experimental medicine trials; Conduct several efficacy trials (planning for these trials would help structure the discussion around scientific questions, vaccine manufacturing capacity, access to and preparation of trial populations, and funding issues); Answer questions regarding protective efficacy of vaccines against different HIV clades and routes of transmission; Strengthen the global HIV vaccine architecture, supporting the role that different national, regional and global organizations that have different audiences, with the Global HIV Vaccine Enterprise playing a critical coordinating role; and Bring new partners to the HIV vaccine field and strengthen interactions with other organizations that work in the HIV prevention arena. 6

7 Cited Literature 1. Esparza J. What Has 30 Years of HIV Vaccine Research Taught Us? Vaccines 2013, 1(4), ; doi: /vaccines

8 Appendix 1. Meeting Agenda Time Speaker Presentation Title 8:00 8:10 Greg Hammond, Alliance Coordinating Office (ACO) Howard Njoo Director General, Centre for Communicable Diseases, Public Health Agency of Canada Welcome and Introduction Theme 1. Optimizing Efforts in HIV Vaccine Development and Clinical Trials 8:10 8:35 Catherine Hankins, Amsterdam Institute for Global Health and Development Department of Global Health, Academic Medical Centre, University of Amsterdam 8:35 9:00 Marc Ouellette, Canadian Institutes of Health Research (CIHR) and Université Laval 9:00 9:25 Stacey Nunes, National Research Council Canada, Human Health Therapeutics Portfolio 9:25 9:50 Joanne Langley, Dalhousie University CIHR-GSK Chair in Pediatric Vaccinology Division of Infectious Diseases, IWK Health Centre 9:50 10:10 Panel/Discussion 10:10 10:30 Break Theme 2. Optimizing Regulatory Practices 10:30 10:55 Dean Smith, Bacterial & Combination Vaccines Division Biologics and Genetic HIV prevention research landscape: Putting HIV vaccine trials in context Encouraging Innovations in Vaccine Research Catalyzing Vaccine Innovation Perspectives from the NRC Innovations in Vaccine Clinical Trials in Canada HIV Vaccine Clinical Trials: How to Optimize Your Regulatory Interaction With Health Canada and Our Regulatory Capacity Building in Africa to Support HIV Vaccine Development 8

9 Time Speaker Presentation Title Therapies Directorate Health Canada 10:55 11:20 Dicky Akanmori, World Health Organization (WHO) Regional Office for Africa 11: :45 Rosanna Peeling, Department of Clinical Research, ITD London School of Hygiene & Tropical Medicine 11:45 12:00 Panel/Discussion Optimizing Regulatory Practices for Vaccine Clinical Trials in Africa Overcoming barriers to development and market entry for point-of-care tests for HIV treatment monitoring and early infant diagnosis 12:00 1:00 Lunch Theme 3. Perspectives from Pharma and International Organizations on Overcoming Barriers for HIV Vaccine Development 1:00 1:25 Marianne Stanford, Immunovaccine Inc. 1:25 1:50 Natalie Charland, Medicago Inc. 1:50 2:15 James Mansi, Novartis Pharmaceuticals Canada Inc. 2:15 2:40 Tony D Amore, Sanofi Pasteur AVP, BioProcess R&D - North America 2:40 3:05 Thomas Hassell, International AIDS Vaccine Initiative (IAVI) 3:05 3:25 Panel/Discussion 3:25 3:40 Break Special Guest Speaker 3:40 4:40 José Esparza, University of Maryland 4:40 4:50 Greg Hammond Closing DepoVax TM : Immunovaccine s Innovative Vaccine Technology Plant-made Virus-like Particles: For Influenza and Beyond Developing Vaccines for the Twenty First Century: from Conventional Vaccinology to Next Generation Technologies Progress in Vaccine Process Development An Industry Perspective Accelerating Development of Vaccines: HIV and Other Major Global Diseases Do We Need a New Paradigm for HIV Vaccine Development? 9

10 alliance-aco.ca