The Zika Virus Challenge: Mapping A Policy Path To Vaccine Development

The lack of preparedness to counter the effects of Zika virus follows a familiar script – a virus known since 1947, but one that has no currently available vaccine or treatments, like many neglected tropical diseases. This case could be illustrative of the wider struggle to finance investments into neglected diseases, but may tell a different story given its rarity of occurrence. It also may demonstrate how the World Health Organization is re-emerging as the global leader on response to outbreaks.

Still fresh from the criticism it received on the management of the Ebola crisis, the World Health Organization recently declared the effects of Zika virus a public health emergency of international concern. These effects are primarily the recent cluster of microcephaly and other neurologic disorders reported in Brazil.

WHO says it has triggered a strategic response plan to address surveillance, response and research. It is also mapping potential projects to coordinate research, to then persuade funders to invest in research and find ways of making vaccines accessible and affordable.

Today, the WHO released a report on the R&D for Zika. It shows there are at least 12 groups working on Zika vaccines, and that all are in the early stages of development and availability of licensed products could take a few years, a WHO official said.

A number of companies have come forth with plans to start developing vaccines, and one Indian company has said they already obtained results in animals with their candidate Zika vaccines, another WHO official said.

WHO is now preparing product profiles for vaccines and diagnostics and will in a few weeks issue advice on priority products in the context of the emergency, the official said.

“Given the interest the current epidemic has awakened, we don’t envisage major problems in terms of investments into developing a vaccine,” she said. “If an emergency vaccine were to be found effective, WHO would enlist appropriate agencies’ contribution (i.e. GAVI) to ensure roll-out in low-income countries susceptible to Zika outbreaks.”

While clearly a neglected tropical diseases, Zika has always been considered a mild virus with few related risks and certainly not life threatening, the official explained. “The recent rise in microcephaly in areas infected with the virus however is making it imperative that we get to know the link between Zika infection and this foetal development problem,” she added. “Should the link be confirmed, it will be critical to find a protective vaccine to prevent future risks for women of child bearing age and their babies (much like we did with Rubella).”

Impact of Zika

The production of vaccines never made a good business case even for diseases higher in the pecking order such as dengue. The case of Zika is more complicated, not the least because there is not enough information on the effects of the virus.

Anthony Costello, who heads the Department of Maternal, Newborn, Child and Adolescent Health at the World Health Organization, said last week, “Even though the Zika virus itself was not life-threatening, the complications of the illness could be potentially devastating for families.” He clarified that the public health emergency designated by WHO would not have been declared for the Zika virus itself (which was a milder virus than dengue and chikungunya), but because of the apparent association with a surge in the number of cases of microcephaly.

The Emergency Committee, convened by the WHO Director-General under the International Health Regulations (2005), agreed that “a causal relationship between Zika infection during pregnancy and microcephaly is strongly suspected, though not yet scientifically proven.”

Microcephaly is a relatively rare condition – affecting between one in three thousand and one in five thousand. Starting January 2014 till now, the Zika virus has spread rapidly and has been reported in 33 countries. This period has also seen a surge in cases of microcephaly particularly in northeast Brazil, WHO has said. Experts have emphasised that correlation is not causation, pending conclusive evidence definitively linking microcephaly as an effect of Zika virus. But Costello called this association “guilty, unless proven innocent.”

However, the lack of enough evidence did not stop WHO from declaring the Zika situation a public health emergency. Costello cautioned that the potential for spread not just across Latin America, but into Africa and Asia, which have the highest birth rates in the world, is also a matter of public health concern, constituting an international emergency.

New Incident Management System

WHO has activated its new incident management system, a product of WHO’s reform process, a WHO spokesperson explained.

The strategic response plan for Zika includes surveillance, response, research. First is to enhance surveillance for Aedes aegypti mosquitoes, Zika virus disease, neurologic syndromes and congenital malformations.

Second, response – which means increasing access to and interventions for vector control, personal protection, risk communications, community engagement and management of neurologic syndromes.

And finally, research – fast-tracking the investigation of the cause(s) of microcephaly, neurologic syndromes and possible association with consequences of Zika virus infection; research and development of new products (e.g. diagnostics, vaccines, therapeutics, etc.).

Having declared the situation as an emergency, WHO is now charting out a plan on the way forward.

A WHO spokesperson told Intellectual Property Watch, “Our first activity is to do a landscape analysis of what is currently in development – or ready to start – to assess which projects are the most suitable and should be accelerated.”

This involves “identifying the most credible projects, then advocating for funders to invest into R&D for these, scoping a potential future market and finally engaging with parties (e.g. GAVI) who could play a role in facilitating access for the poorest countries to a future vaccine,” she said.

Global health experts, such as Prof. Lawrence O. Gostin at Georgetown University, are of the view that WHO must set the research agenda.

“WHO needs to use its international leadership and legitimacy to mobilize funding and coordinate research. There is a great deal WHO could do,” he said in an email. “First, it should mobilize international funding for R&D making it a priority for NIH and other funders. Second, it should use its convening power to share data and research results among researchers. Third, it should coordinate all the disparate research activities to concentrate and combine global efforts and drive the research agenda.”

Since Zika’s new status as an emergency, there has been expectedly a rash of announcements mostly by the private sector on new projects for vaccines. This frenzied activity comes as no surprise. Now that a market for drug for Zika virus has emerged, there is inevitably going to be a delay in such drugs coming into the market.

“Vaccine research and development is a lengthy process, typically taking 10-15 years”, a spokesperson for GlaxoSmithKline said in an email. The company invested around nearly $145 million in the accelerated development programme for Ebola vaccine, the company spokesperson added.

The most pessimistic estimate is 20 years for a Zika vaccine, and the most optimistic is a human clinical trial before the end of this year. According to WHO’s cautious estimate, the world is at least a year or two away from the first vaccine for Zika virus.

The hunt for a vaccine for Zika faces a fundamental problem – the fact that there is what experts call “a data vacuum” on the virus itself. WHO acknowledges that “there are considerable gaps of knowledge at the moment about the Zika virus and the etiology of microcephaly,” a spokesperson said.

A slew of big pharmaceutical companies, smaller companies and public sector agencies are in the race for new drugs for Zika. Sanofi Pasteur, GlaxoSmithKline, Inovio Pharmaceuticals, Bharat Biotech, among others, are some of the companies who have said that they are already working or are planning working on Zika. The Public Health Agency of Canada and US National Institutes of Health have reportedly started work on potential candidates for Zika vaccine.

Jeffrey Richardson, spokesperson for the US-based Inovio Pharmaceuticals told Intellectual Property Watch, “We expect to be in a human clinical trial by the end of this year.” The company is working on a DNA-based vaccine that contains no killed or weakened virus. It is a synthetic product that can be and manufactured faster than traditional vaccines, he added.

However, some analysts have cautioned that several stages of the clinical trial and a subsequent regulatory approval could take some time.

Both Zika and dengue belong to the same family called flavivirus. Researchers hope that understanding on dengue will contribute to finding a vaccine for Zika.

Sanofi Pasteur recently launched its dengue vaccine, Dengavaxia, and is also working on a vaccine candidate for Zika.

“We hope to leverage our existing expertise, technologies and infrastructure for our recently licensed dengue vaccine against the Zika virus to rapidly advance a vaccine candidate,” Nicholas Jackson, head of research for Sanofi Pasteur told Intellectual Property Watch. “Today we are at the early research phase. Our established dengue collaborative network will significant support R&D efforts to find a vaccine against Zika.”

Having successful vaccines candidates is only part of the battle. “Getting industry to share data is hard given their intellectual property rights and search for profits,” Georgetown’s Gostin pointed out.

Fixing the Model to Incentivise Research

There has been no business case for investments in vaccines, although it makes great economic and fiscal sense for governments to have vaccines ready to address outbreaks as they emerge. Clearly, this situation is not limited to the effects of Zika virus alone. It may have to do with the wider failures of getting markets to invest in public goods such as drugs for neglected diseases – those predominately afflicting poor populations.

WHO has initiated several processes underway to find ways to finance research into neglected diseases and crucially, to delink profits from R&D.

Three years ago, it adopted a resolution that supported a strategic workplan to improve monitoring and coordination, and to ensure sustainable funding for R&D. During spring this year, the WHO will convene a meeting to assess the progress on the work plan.

Ahead of the 69^th World Health Assembly in May, this meeting will consider the work of the Consultative Expert Working Group on Research and Development: Financing and Coordination (IPW, Public Health, 4 February 2016). Some of the initiatives include the establishment of the WHO Global Observatory on Health Research and Development, launched in January, which will collect and collate data on funding for health research and development, health products in the pipeline, clinical trials and research publications.

WHO is also developing an “R&D Blueprint” that will review options and devise a new paradigm for a global effort to enhance R&D preparedness for future epidemics.

In its note calling for public consultation, WHO said, “market-driven models for R&D do not cater for medical technologies for diseases that are sporadic or unpredictable, especially when they occur in countries with low investment in health infrastructure and delivery.” (There is no commercially available diagnostic test for Zika.)

WHO has called for ideas on improving R&D readiness for priority infectious disease threats. Specifically, propositions are requested for flexible development and production platform technologies, the WHO said in its note.

“There needs to be public-private partnerships. Clearly, the pharmaceutical industry will not invest heavily in a vaccine, diagnostic test, or antiviral without the right incentives. By incentivizing industry and forming partnerships it would be a powerful combination. These partnerships could combine the WHO, relevant governments and other donors, and the private sector,” Gostin said.

There is no straightforward way out on financing investment into research. From faster clinical trials, to advance purchase commitments, to pooled voluntary funds, a range of suggestions have been discussed in the past.

“It is critical that we find ways to better coordinate bio preparedness R&D activities for vaccines, diagnostics, treatments, and related tools to fight pathogens that are most likely to cause epidemics and that we can ensure access to manufacturing capacity to make them when required,” a GSK spokesperson said.

Depending on Developed Countries, Pharma

WHO Legal Counsel Gian Luca Burci said in a recent statement: “The WHO has taken the lead in coordinating the international response to Zika while trying to avoid the overreactions that led to the unnecessary isolation of the three African countries mostly affected by Ebola. However, the situation is very fluid and much will depend on the commitment of developed countries and pharmaceutical companies for the mobilization of resources and the rush to quickly produce a viable vaccine.”