LONDON – The World Health Organization (WHO) has released its COVID-19 R&D roadmap, highlighting the gaps in knowledge about the virus and setting out priorities for research. The organization is now calling on groups around the world to use the document – drawn up by 400 experts – to coordinate their efforts.
“We’re very encouraged by the level of interest around the world in accelerating research as part of the response,” said Tedros Adhanom Ghebreyesus, WHO director general, announcing publication of the plan. “It is vital to coordinate research so that different groups around the world complement each other, so WHO can give better advice, and countries can take evidence-based decisions that save lives,” he said.
The research roadmap is backed by a core set of protocols WHO has developed outlining how clinical studies should be designed and how data are collected, to ensure it is possible to compare and pool data from multiple clinical studies.
The roadmap was published as the European Commission announced an additional €37.5 million (US$42.8 million) toward the development of vaccines, therapeutics and diagnostic tests, bringing the EU’s total commitment of funding and in-kind contributions from companies involved in collaborative projects to €140 million.
At the same time, the government in Germany said it is putting €10 million into COVID-19 research, and the U.K. government announced £46 million (US$60 million) to fund vaccine projects and the development of a point-of-care diagnostic for the new coronavirus.
The U.K. government previously has given £30 million to the Coalition for Epidemic Preparedness Innovations (CEPI) to support its work developing vaccines against emerging infectious diseases, and of the £46 million in new funding, £20 million is going directly to CEPI, to keep newly established COVID-19 vaccines programs on track.
CEPI said it has committed $100 million of its own funds to speed up COVID-19 programs, with the aim of getting constructs into first-in-human trials within four months. However, those funds will be fully allocated by the end of March. “Without immediate additional financial contributions the vaccines programs we have begun will not be able to progress,” said Richard Hatchett, CEO of CEPI, making an urgent call for $2 billion to get to the point of submitting three vaccines for regulatory approval in 2021.
The WHO research roadmap and fresh funding commitments came as every country in Europe, apart from Cyprus, was confirmed to have cases of COVID-19. The total number of cases in Europe was 11,577, as of March 9. In Italy, which is the worst affected, the government has imposed travel and other restrictions affecting 16 million people in the north of the country.
Worldwide, there have now been more than 100,000 reported cases in more than 100 countries, and more than 3,650 deaths.
Ghebreyesus said that to date WHO has received applications for review and approval of 40 diagnostic tests, 20 vaccines and an (unspecified) number of therapeutics. There are more than 200 clinical trials targeting COVID-19 progressing in China. Those include 35 studies evaluating antivirals and other agents, including remdesivir (GS-5734), the protease inhibitor combination drug Kaletra (lopinavir +ritonavir), Truvada (tenofovir),Tamiflu (oseltamivir), Xofluza (baloxavir marboxil), Arbidol (umifenovir), interferon drugs, the antimalarial drug chloroquine, and Lianhua-Qingwen, a traditional Chinese medicine for treating flu.
To back clinical development of those and other drugs, the WHO roadmap says research to better understand in vitro and in vivo activity, pharmacokinetics and pharmacodynamics, work on dosages and route of administration is “crucially needed.”
In addition, there is an “urgent need” to identify and/or develop adequate animal models. There also is insufficient knowledge of the clinical evolution of COVID-19 and its epidemiology, to guide the choice of patient populations and endpoints for efficacy trials, and the clinical window for treatment with antivirals and other agents needs to be defined.
Building on previous work to develop vaccines against the SARS and MERS coronaviruses, a number of vaccines against COVID-19 have moved swiftly into animal studies. However, the WHO R&D roadmap highlights various questions that remain about how development should proceed and be fast tracked.
The major concern is that animal studies of some, but not all, vaccine candidates against the related coronaviruses, have shown enhanced disease can occur in immunized animals upon subsequent exposure to live virus.
“Evaluating the potential for enhanced disease in humans is critical before [vaccines] can be assessed through larger-scale studies, the roadmap says.
WHO intends to set up a new expert group working on animal models, and another to advise on the development and standardization of assays to evaluate immune responses and for use in GMP manufacturing.
To support phase IIb/III vaccines studies, WHO is developing a master protocol and says key decisions still need to be made about the design of later-stage trials.
WHO is working on a target product profile for COVID-19 vaccines to guide vaccine developers and will set up a web-based platform for data sharing.
Despite the large amount of information that has accumulated about COVID-19 infection in the past two months, there are still gaps in the knowledge of its basic biology. WHO wants to see a review of the evidence as to the animal host(s), to prevent continued spillover and increase understanding of the transmissibility.
Funding agencies represented at the two-day meeting in February, when the R&D roadmap was drafted, agreed they would use the priorities set out by WHO to synchronize their existing investments and inform deployment of any additional resources.
“The focus is on how the efforts of a large number of the world’s funders of global health R&D could be coordinated and optimized,” WHO said.
Funding for vaccine development
CEPI is working in cooperation with WHO on vaccine development. Of the $2 billion it is seeking to advance three vaccines to submission for regulatory approval, CEPI said it needs $375 million by the end of March for manufacturing of clinical trial material for phase II/III trials of four to six vaccine candidates and for initial investments to expand global manufacturing capacity to ensure any vaccine is ultimately available at scale and globally.
By the end of June, CEPI will need a further $400 million to carry out phase II/III trials of at least two candidates; prepare the ground for a number of other trials at different locations; manufacture more clinical trial material; and for further investment in scaling up manufacturing of six candidates.
The aim then is to raise a further $400 million by the end of September for phase II/III trials of an additional four candidates in a number of locations globally, and to build large-scale manufacturing capacity for at least three vaccine candidates.
Following that, $500 million to $750 million is required in 2021 to further support global manufacturing capacity for up to three candidates at a number of locations, the completion of clinical trials, and regulatory and quality requirements for at least three vaccines, and the preparation of regulatory files to submit for emergency authorization.
To ensure availability of funds and in view of the many uncertainties surrounding COVID-19, CEPI has a mechanism whereby funds can be returned to donors if not used for the response, or if the epidemiological picture changes and vaccine development is deemed unwarranted.