Long term thinking is needed to handle zoonotic disease threats! Meet Dr Beth-Ann Coller, Ebola vaccine director at Merck & Co Inc.
– Clinical trials carried out in the midst of an epidemic, and the fact that we soon hope to provide an efficacious prophylactic vaccine against Ebola Zaire, is the result of the collaboration between a number of highly experienced partners says Dr. Beth-Ann Coller, Executive Director with Merck & Co., where she leads the product development of vaccines against Ebola and other zoonotic diseases. Dr Coller is one of the keynote speakers at Uppsala Health Summit in October.
In this article, Dr. Beth-Ann Coller describes the role played by Merck in this process and the experiences gained along the way.
The process of developing an efficacious vaccine protecting against the Zaire Ebola virus involved scientists and experts from international and national health organisations, NGO:s, industry and academia. While the pre-clinical research and manufacturing activities leading up to vaccine doses that could be tested in clinical trials were carried out by Canadian researchers, the substance was later licensed to industry, and sub-licensed to Merck & Co. Inc., or MSD as the company is known outside of the United States and Canada. The company is now preparing for licensure of the vaccine by the FDA, the EMA and national medical authorities.
A project involving many critical partners
– I think the most important role played by Merck in this process has been the coordination between all partners, says Dr Coller. These include i.a. the WHO together with national public health authorities like the Guinean Ministry of Health and Public Hygiene, NGOs like Médécins Sans Frontières who carried out critical work on the ground; and a number of funders1).
– A second role, also critical to the project’s way towards the patients, is as regulatory sponsor for the product, providing all data to regulatory agencies, and assuring that the regulatory process is followed and the much-awaited licensure is reached.
– Finally, we are now setting up production of the vaccine, bringing the actual product to the market, and looking to put the necessary contracts with public health authorities and NGO:s in place to make sure that the vaccine will be available once licensure is obtained.
Clinical trials in the midst of an epidemic
The clinical trials received considerable attention internationally both for taking place in the midst of an epidemic and for using the ring-vaccination approach. The trials were conducted by the WHO and Médécins sans Frontières in Guinea, by the United States CDC in Sierra Leone and by the United States NIH in Liberia.
– Many feared that the trials would detract resources from fighting the outbreak, Dr. Coller comments, but the carefully and well-designed trials may have actually helped putting an end to the Ebola crisis.
– The ring vaccination trial was a great experience, a great model for testing new vaccines and drugs against infectious diseases, and it was developed with expertise from the WHO. The design, inspired by small-pox eradication in the 1970’s, was efficient and worked even during the challenging circumstances that prevailed in Guinea at that time, Dr. Coller explains.
– This may be one of the most important lessons learnt from this project, Dr. Coller continues, an experience, of great use for the future, together with the understanding that we actually can conduct good clinical research in the midst of an urgent health situation if carefully and thoughtfully planned.
Long term R&D is needed!
Another important experience for the future development of vaccines and treatments against infectious diseases is the importance of long term thinking in research and development.
– When the Ebola crisis struck Western Africa, good quality research had already been conducted and there was access to pre-clinical research data and to clinical grade vaccine doses that we could start working with in clinical phase I trials, says Dr. Coller. - While preparing clinical protocols in advance can be useful for speeding up implementation, having access to good pre-clinical research data and clinical grade supplies is critical.
- Today we are starting to see some interesting breakthroughs against Zika virus. Unfortunately Zika research was not at the same stage as Ebola research was. Testing of new vaccines and medicines has therefore lagged behind the epidemic. This epidemic appears to be waning, thankfully, but this means that there are also fewer opportunities to test new vaccines and medicines.
Public-private partnerships, like CEPI - the Coalition for Epidemic Preparedness Innovations, will continue to fill a critical role, assembling and prioritizing targets, bridging the gaps between actions and actors in early phases of development. Basic research and early development work needs to be encouraged!
Does industry have a role to play in developing treatments against infectious diseases?
- How to translate basic science research into the making a new drug, a new vaccine, is a core competence for industry. But public health authorities should plan for access and for rolling out vaccine plans. The experiences from the development of the Ebola vaccine also underline the need to involve partners who can carry out the trials on the ground and plan for its implementation. This are really complementary skills that translate into a continuum, says Dr. Coller.
- As a vaccine developer and producer, we aim to see that the final product, apart from being efficacious and safe, is as easy as possible to use. To assure adequate access to the vaccine, when and where needed, requires careful planning. However deciding upon who to vaccinate is a task for public health authorities.
– In this particular case, GAVI and the WHO are working together to estimate the number of adequate doses that should be available, in addition to the work done by national authorities. WHO and UNICEF likely will be involved in the management of a strategic stock of the vaccine, as they already do for other similar products.
We have to work broadly on zoonotic diseases!
Even if the world will soon have access to an Ebola vaccine, new and re-emerging infectious disease threats will continue to demand efforts of various types to prevent and manage outbreaks.
- Our perspectives on what are the most urgent disease or areas to focus upon will always differ depending on where we sit in the world, Dr. Coller comments when asked about where to focus research and development next.
- Pandemic influenza is a huge challenge, and a lot of good work has gone in there, making us so much better prepared today than we were at 1918 influenza epidemic outbreak. But there is still a lot more to do in this area, and a lot of work to do to be able to handle disease like MERS, Zika and Chikungunya. The way we continue to expand our footprint in the world impinging on animals in the wild and with the ongoing climate changes things will not get any better, and we need to work broadly on zoonotic diseases to be handle to handle the threats they will continue to pose.
- I am looking forward to Uppsala Health Summit in October, to hearing from others’ experiences of combatting infectious disease outbreaks. One thing we have learnt from developing the Ebola vaccine, is that we must continuously work on gaining insights and learning from others’ ongoing research.
1) The extensive partnerships that have been pivotal for the rapid progression of the development of the rVSV-ZEBOV-GP vaccine (V920), include:
- Global public health organizations (e.g. WHO, Médecins sans Frontières [MSF]),
- Governmental agencies (e.g. Public Health Agency of Canada [PHAC], US National Institutes of Health [NIH], US Centers for Disease Control and Prevention [CDC], Norwegian Institute of Public Health [NIPH]),
- Clinical researchers (e.g. the WHO-led VSV Ebola Consortium [VEBCON], Canadian Center for Vaccinology, Walter Reed Army Institute of Research [WRAIR], Sierra Leone Medical School, Liberia-US clinical research partnership),
- Funding organizations (The Wellcome Trust, the Global Vaccine Alliance [GAVI], the Biomedical Advanced Research and Development Agency [BARDA], the Defense Threat Reduction Agency [DTRA], Joint Vaccine Acquisition Program [JVAP]),
- Vaccine developers (NewLink Genetics and MSD)
- Regulatory agencies and Minstries of Health (e.g. US Food and Drug Administration, European Medicines Agency, Health Canada, Ministry of Health and Social Welfare of Liberia, Ministry of Health and Public Hygeine of Guinea, Ministry of Health and Sanitation of Sierra Leone)