LONDON – As the epicenter of the COVID-19 epidemic shifted to Europe and the number of deaths in Italy exceeded the toll in China, the EU stepped up efforts to mount a coordinated response, with a big boost for collaborative R&D funding and a call for clinical research to be pooled in multicenter, multi-arm randomized controlled trials.
Pledges include €137.5 million (US$146.8 million) from the EU’s Horizon 2020 R&D program for academic research, €164 million from the European Innovation Council for small companies working to commercialize relevant products and a €80 million loan guarantee for German biotech Curevac AG to support manufacturing of its messenger RNA COVID-19 vaccine candidate.
In addition, the EU has given €130 million to the World Health Organization (WHO), to support the response on the ground.
At the same time there have been moves to encourage staging of pan-European clinical research, with the EMA saying the large number of small trials of possible COVID-19 treatments that are being planned across the EU will not generate high-quality evidence. “Such studies would not be in the best interest of patients,” the agency said in a statement on March 19.
The EMA also is highlighting the need for more global cooperation, as co-chair with the FDA of the first regulatory workshop on COVID-19, held on March 18. The virtual meeting, involving 20 national regulators, discussed development of vaccines against the coronavirus.
The EU’s first announcement of research funding dedicated to COVID-19 was of €10 million in late January, when the virus was confined to China and the possibility of a global pandemic seemed remote. That sum subsequently was increased to €47.5 million, as the crisis unfolded.
What is more notable than the amount of money, is the speed with which it has been allocated. All research proposals were evaluated with two weeks and while the names of the winners have not been announced, 17 vaccines, treatments and diagnostics projects, involving 136 research teams have been awarded grants.
A further €45 million from Horizon 2020 is being channeled through the Innovative Medicines Initiative (IMI), a public-private partnership with the pharma industry. The EU cash will be matched by in-kind contributions from companies.
IMI projects must involve three partners in three different countries, and in more conventional times grants are awarded around eight months after the call deadline. In the case of COVID-19, Pierre Meulien, director of IMI, has promised the first projects will be ready to start in June.
Meulien referenced IMI’s response to the West Africa Ebola epidemic, when it launched a call to develop a vaccine at the start of 2014. That led to the first IMI-funded vaccine trial in April 2015. “During the outbreak of Ebola, we demonstrated IMI can rapidly launch projects and deliver results … I am confident we can do it again,” Meulien said at the launch of the COVID-19 call.
IMI also has been keen to point out it already supports relevant projects, having put €104 million into coronavirus research over the past nine years. One example is the Zoonotic Anticipation and Preparedness Initiative (ZAPI), launched in 2015 to set up tools and platforms to be ready to vaccinate domestic animals against emerging zoonoses, lowering the risk of transmission to humans.
In the current context, ZAPI looks particularly prescient, Meulien claims. “In 2019, the project demonstrated that certain antibodies can stop the MERS coronavirus from infecting new cells,” he said. Now ZAPI researchers are assessing if the same antibodies are effective against the COVID-19 virus.
Meulien said IMI is aware pharma companies have clinic-ready assets originally developed to treat other viral diseases that could be repurposed for COVID-19. “The public-private model lends itself well to this scenario because our pharma partners can be mobilized to share what they know,” he said.
There is “little or no immediate commercial advantage” for companies, but working with academic researchers can speed the validation of platform technologies and manufacturing processes.
The EMA is keen to ensure any COVID-19 trials getting off the ground with EU or national government funding are set up in a harmonized way, with a robust methodology for collecting results. A number of hospitals and academic groups are planning COVID-19 studies, or are treating patients under compassionate use protocols.
It may seem harsh in the current context when there are no approved treatments, but the EMA recommends studies should be randomized and placebo controlled.
As things stand, the number of small studies and compassionate use programs across Europe are unlikely to be able to generate the required level of evidence to allow clear-cut recommendations, according to the EMA.
The EMA statement was echoed by WHO Director General Tedros Adhanom Ghebreyesus, speaking on March 18, at the launch of WHO’s multicountry Solidarity clinical trial. “Multiple small trials with different methodologies may not give us the clear, strong evidence we need about which treatments help to save lives,” Ghebreyesus said.
WHO and its partners are therefore organizing the Solidarity study, in which untested treatments are compared with each other. WHO has designed a simplified protocol to enable even hospitals that are overloaded to participate.
“This large, international study is designed to generate the robust data we need, to show which treatments are the most effective,” said Ghebreyesus.
The COVID-19 Solidarity Response Fund to pay for the trial has raised more than $43 million from more than 173,000 individuals and organizations, in the few days since WHO launched it.
Countries that have already confirmed that they will join the Solidarity trial include Argentina, Bahrain, Canada, France, Iran, Norway, South Africa, Spain, Switzerland and Thailand. “I trust many more will join,” Ghebreyesus said.