By Timo Minssen
The current Ebola outbreak already attracted much attention on “Bill of Health” resulting in some excellent blogs on a horrible topic.
While it is evident that the current health crisis requires both immediate responses and more sustainable changes in health care policy, research and regulation, medicines regulators are collaborating internationally to find innovative solutions enhancing evaluation of and access to potential new medicines to fight Ebola outbreaks. In a statement announced by the International Coalition of Medicines Regulatory Authorities (ICMRA) in September 2014, regulators around the world led by the FDA and the EMA have vowed to collaborate in supporting accelerated evaluation of experimental new drugs to treat Ebola virus infections and say they will encourage submission of regulatory dossiers. This clearly backs up the World Health Organization’s (WHO) decision to test experimental Ebola treatments in infected patients in the current outbreak region in West Africa and to speed up the development of vaccines.
In the following I would like to summarize and discuss some of the recent European responses to the current crisis starting with an overview on recent initiatives at the EMA.
Like its US counterpart, the EMA leads a close and consistent dialogue with public and private developers of Ebola products and spends much effort in reviewing available information on the various experimental Ebola treatments currently under development. These experimental drugs range from experimental antivirals or vaccines based on the adenovirus or stomatitis vaccine to experimental therapies based on mono- and polyclonal antibody technologies. One of these unapproved antibody combination drugs – MAPP Biologicals’ ZMapp – has already been used in some care workers affected by Ebola. Other experimental drugs that are currently reviewed by the EMA include Biocryst’s BCX 4430, Fab’entech’s Hyperimmune horse sera, Sarepta’s AVI-7537, Toyama Chemicals and MediVector’s Favipiravir and Tekmira’s TKM-Ebola.
In addition to monitoring experimental drugs and enhancing global collaboration, the European Medicines Agency has like the FDA initiated several activities in order to support and speed up the development of these drugs towards market approval.
These activities encompass the establishment of a European expert group with special skills in clinical trial design, vaccines and infectious diseases. To enable this expert group to support developers of experimental Ebola treatments in the most efficient way, the EMA has implemented a so-called “rolling review” system. It allows experts to continuously assess incoming data and to share subsequent updates with healthcare decision-makers in concerned countries. In addition to the enhanced data review, the EMA has also established “rapid scientific advice and protocol assistance procedures” on scientific and regulatory matters. The accelerated procedure allows individual developers to immediately ask for expert advice for example on questions related to improving production processes, the design of clinical trials or pharmacovigilance.
Interestingly, on October 29th, 2014 EMA announced that it has given the first “rapid scientific advice” since the current Ebola outbreak to GSK on its development plan for an vaccine consisting of a common cold virus, called an adenovirus, modified to carry two genes of the Ebola virus. Animal testing has demonstrated that when the adenovirus infects cells the Ebola genes express harmless proteins, which stimulate the immune system to produce antibodies to Ebola.GSK had previously announced that the experimental vaccine was being fast-tracked into human studies. If the results are positive, GSK plans to build a stockpile of up to 10,000 doses for emergency uses.
In addition to providing improved organizational frameworks and devising more efficient pathways for an accelerated market approval procedure for experimental Ebola treatments, the EMA also encourages developers to submit applications for orphan designation to EMA and FDA in parallel. As it is stressed in a recent EMA announcement: “medicines with recognised orphan status have access to a range of incentives to stimulate development and facilitate placing on the market. This includes free scientific advice from EMA, fee waivers and 10 years of market exclusivity once the medicine is authorised. Applications for orphan designation of Ebola medicines will be treated as a priority and EMA has committed to fast-tracking their evaluation.”
Although, the advantages by market based mechanism, such as orphan drug designations granted by the EMA, are substantial and might provide important incentives for private investments in Ebola related research, it is clear that EU public funding and involvement in Ebola research and monitoring will remain crucial.
The European Commission has been monitoring events closely in cooperation with the European Centre for Disease Prevention and Control (ECDC) and the WHO since news of the outbreak first broke in March 2014. The ECDC is producing risk assessments, epidemiological updates and other information, such as travel warnings. Moreover, on 6 November 2014 the European Commission and the European pharmaceutical industry launched a €280 million call for proposals under the Innovative Medicines Initiative (IMI) to boost EU research on Ebola. The funding will cover urgent actions addressing the current epidemic and put in place a long-term strategy to manage any future outbreaks.
However, these immediate responses can only be the first step and more sustainable changes in health care systems, clinical trials design and regulatory approval pathways are needed in order to allow for quicker and better co-ordinated responses in future scenarios. In addition we need to further evaluate legal alternatives to market-mechanism based incentives and we need better economic research in rare diseases and “ebolanomics” to do the job. While the current Ebola crisis has clearly necessitated an “ebolution” of clinical trials design and operation, the rapid approaches have generated myriads of ethical and legal questions that must be addressed in order to create a more robust ethical and legal basis for such actions. The lessons to be learned from the current dilemma have been eloquently described in a recent NEJM perspective article by the FDA chief scientist Jesse Goodman: “When it comes to infectious diseases, we are increasingly one world and dependent on each other for knowledge, safety, and security.”