08 Apr 2021

LIVE BLOG: R&D response to COVID-19 pandemic

Covid 19 blog

The coronavirus pandemic is disrupting universities and research institutes across the world. But the same institutions are also working very hard to find out how the disease can be stopped and its effects mitigated.

Follow this live blog for the latest updates on how the crisis is impacting research and innovation, and what governments, funders, companies, universities, associations and scientists are doing to stop or cope with the pandemic.

You can read the full archive of this blog here.

 

Pfizer and BioNTech have announced an agreement with the European Commission to supply an additional 200 million doses of their COVID-19 vaccine Comirnaty, to the EU.

This new agreement is in addition to the 300 million doses that have already been committed to the EU in 2021 under the first supply agreement signed last year. The additional 200 million doses are expected to be delivered in 2021, with an estimated 75 million to be supplied in the second quarter.

The total number of doses to be delivered to the EU member states by the end of 2021 is now 500 million, with the potential to increase to 600 million based on an option granted in the new agreement.

Albert Bourla, CEO of Pfizer said, “With this new agreement with the European Commission, we now expect to deliver enough doses to vaccinate at least 250 million Europeans before the end of the year.”

“We have taken additional steps to expand our manufacturing capacity to two billion doses in 2021,” said Ugur Sahin CEO of BioNTech. “We will initiate production at our Marburg facility this month.”

 

The UK government has awarded funding to extend its support for COVID-19 clinical trials to the earliest phase I studies, making it possible to rapidly progress new therapies through all stages of development in the country.

Four therapies have so far been selected for phase I development. Future treatments will be selected by the UK COVID-19 therapeutics advisory panel, which is open to receiving proposals from academic groups and companies.

Currently, the government is funding phase II and III studies, including the large scale Recovery trial, which is testing existing drugs in hospitalised COVID-19 patients. The randomised study, which recruited its 36,000 patient last week, has found two therapies, dexamethasone and tocilizumab, that are effective, and shown that four suggested treatments are not.

Phase I trials are the essential first step that ensures treatments are safe. The government backing is for Agile, a phase I/IIa clinical trial platform run in a collaboration between Liverpool, Lancaster and Southampton universities, and other external partners

The design of the platform means that multiple potential treatments can be evaluated in parallel and testing can be completed in months rather than years.

Patients in the early stages of COVID-19 infection will be recruited to Agile from the community, in addition to patients who have been hospitalised with COVID-19. Drugs that show a signal of benefit in Agile will be considered for advancement into later phase clinical trials.

 

Policymakers should learn lessons from the success of research and development (R&D) in responding to COVID-19, to rethink approaches to tackling healthcare and environmental challenges, according to a new study.

Economists from Bath University and the International Monetary Fund examined the drivers of innovation in global pharmaceutical R&D, finding research carried out by the industry typically follows a law of diminishing effort. This means that while the global death burden of a disease doubles, the intensity of research effort rises by only 50%.

However, the scientific response to COVID-19 is a major exception, with seven to twenty times more COVID-19 clinical trials than this historical relationship would imply.

During the pandemic, global pharmaceutical R&D, as measured by the number of clinical trials, has scaled up by 38%, with only a modest reduction of research on other diseases.

But much of this response occurred via public research institutions, which account for 70% of all COVID-19 trials globally.

The researchers say their findings suggest global pharmaceutical innovation has room to grow, but that government incentives and support from public research institutions should play a crucial role in supplementing the private research.

Patrick Gaule, senior lecturer in economics at Bath University and co-author of the study said, “The rate and direction of innovation is shaped by incentives and government policy actions. Traditionally, economists have emphasised the market size as an important driver for innovation - the greater the private demand for an innovation, the more innovation we should expect in that domain.”

"However, this may not be sufficient by itself to encourage innovation to address the deadliest diseases - from coronary heart disease to lung cancer, or indeed other major challenges facing humanity, namely climate change.”

Instead, the response to COVID-19 suggests that scaling up global innovation in the future may require moves to complement the market size effect with early-stage incentives that harness the power of public research institutions and non-monetary incentives, for example altruism, Gaule said.

 

The European Medicines Agency said it is developing guidance for manufacturers planning changes to existing COVID-19 vaccines, to tackle emerging new virus variants.

The agency has asked all vaccine developers to investigate if their vaccine offers protection against new variants, such as those first identified in the UK, South Africa and Brazil, and submit relevant data.

EMA will then publish guidance on what data and studies are needed to support modifications of existing vaccines to current or future mutations of SARS-CoV-2 in the EU.

Questions that will be addressed include: what are the options for introducing a new variant into an existing approved vaccine?; what will be required to demonstrate quality, safety and efficacy of modified vaccines?; which bridging studies will be required to provide adequate reassurance of a vaccine’s efficacy against a new variant, either as first vaccination or as booster?

EMA has authorised three vaccines for use in the EU and there are concerns that some mutations could impact to different degrees the ability of the vaccines to protect against infection and disease.

A reduction in protection from mild disease does not necessarily translate into a reduction in protection from serious disease, but more evidence is needed.

Variants of SAR-CoV-2 have been present since March 2020, spreading even before the start of vaccination campaigns.

EMA is working with other regulators in the International Coalition of Medicines Regulatory Authorities to determine possible changes to the composition of COVID-19 vaccines and to align global strategy.

BioNTech has started manufacturing at its new Marburg facility, making the first batch of mRNA for its COVID-19 vaccine. The batch will produce enough active ingredient for eight million doses of the vaccine, the company said.

After initial production, the raw material will be purified and concentrated, before being encapsulated in lipid nanoparticles that both protect the mRNA and deliver it to the target lymphoid cells, generating an immune response.

Before the vaccine can be shipped the European Medicines Agency will review quality and validation data from the first production batches. This will take place in February and March. Based on approval by the EMA, the initial batches of the vaccine will be delivered to other sites to be put into vials.

BioNTech said it is working with co-developer Pfizer to respond to global demand, increasing manufacturing capacity to up to two billion doses of vaccine in 2021. However, that assumes continuous process improvements, expansion at current facilities and adding new suppliers and contract manufacturers.

It also depends on updating the label on the vials, to allow six doses per vial, rather than five, as envisaged in EMA’s original approval.

Last week, Pfizer announced the modification of production processes at its facility in Puurs, Belgium, which has held up supplies, has been successfully completed. That has put the company back on track to meet the original schedule of vaccine deliveries to the EU in the first quarter, and supply up to an additional 75 million doses to the EU in the second quarter of 2021.

The initial EU order for 300 million doses in 2021 was subsequently increased to 500 million when the contract was amended in January.

The new BioNTech site in Marburg will become one of the largest mRNA manufacturing sites in Europe with an annual production capacity of up to 750 million doses, once fully operational.

BioNTech plans to produce up to 250 million doses at the facility in the first half of 2021, with the first vaccines manufactured at the Marburg site scheduled for distribution in early April.

 

COVID-19 has reduced the share of electricity generated by burning coal - a trend that could outlast the pandemic, according to a new German study. Researchers in Potsdam and Berlin found a window of opportunity has opened to make the current fall in coal use irreversible and say that supported by the right climate policy measures, power sector emissions could decline more rapidly than previously thought.

"Coal has been hit harder by the corona crisis than other power sources,” said Christoph Bertram from the Potsdam Institute for Climate Impact Research, lead author of a paper in Nature Climate Science. "If demand for electricity drops, coal plants are usually switched off first. This is because the process of burning fuels constantly runs up costs. The plant operators have to pay for each single ton of coal. In contrast, renewable power sources such as wind and solar plants, once built, have significantly lower running costs and keep on operating even if the demand is reduced."

In 2020 overall global CO2 emissions from the power sector decreased around 7%. In India, the US, and European countries, where monthly electricity demand declined by up to 20% compared to 2019, the fall was more marked, with monthly CO2 emissions down by up to 50%.

As long as clean electricity generation growth exceeds increases in electricity demand, CO2 emissions from the power sector will decline, because the pandemic has weakened the market position of coal-fired power generation and illustrated its vulnerability, the researchers say.

Co-author Ottmar Edenhofer, director of the Potsdam Institute and the Mercator Research Institute on Global Commons and Climate Change said, "In the end, it will certainly take carbon pricing to cut emissions at the required pace and stabilise our climate. Yet the impacts of the corona crisis on the power generation sector have put political leaders in a unique position. Along with additional policies such as eliminating subsidies for fossil fuels and increasing investments in wind and solar power, it is now easier than ever before to put an end to high-carbon electricity."

 

A clinical trial looking into alternating COVID-19 vaccines launching in the UK today will examine whether different vaccines can safely be used for a single person.

The study, backed by £7 million of government funding, will be the first in the world to assess the effects of using different vaccines for the first and second dose, for example, Oxford University/AstraZeneca’s vaccine for the first dose, followed by Pfizer/BioNTech’s vaccine for the second, and vice versa.

It will also gather evidence on whether different intervals between the first and second dose have an impact on the immune response.

The trial will recruit 820 volunteers over the next 2 – 3 weeks, at eight sites across the UK. It is not studying efficacy, but rather assessing the immune response to mixed vaccination. Initial results are expected in June.

As they are approved and become available, other vaccines will be added to the study.

Matthew Snape, principal investigator, said if mixed schedules are as good as two doses of the same vaccine, it will provide more flexibility with vaccines rollout and help deal with any disruption to supplies.

Deputy chief medical officer Jonathan Van-Tam said, “Given the inevitable challenges of immunising large numbers of the population against COVID-19 and potential global supply constraints, there are definite advantages to having data that could support a more flexible immunisation programme.”

It is also possible that by combining vaccines the immune response could be enhanced. “Unless this is evaluated in a clinical trial we just won’t know,” Van-Tam said.

UK pharma company GlaxoSmithKline and German biotech CureVac announced a new €150 million collaboration to jointly develop next generation mRNA vaccines for COVID-19, aiming to provide protection again multiple variants of the SARS-CoV-2 virus that are emerging in a single vaccine.

GSK will also use its manufacturing facilities in Belgium in support of the manufacture of up to 100 million doses of CureVac’s first generation COVID-19 vaccine CVnCoV in 2021, which is in a phase IIb/III trial.

In the co-development agreement, GSK and CureVac will share resources and expertise to develop a vaccine offering broader protection against different SARS-CoV2 variants, and to enable a quick response to new variants that emerge in the future. The development programme begins immediately, with the target of introducing a vaccine in 2022, subject to regulatory approval.

GSK will make an upfront payment to CureVac of €75m and a further payment of €75m, conditional on the achievement of specific milestones.

The vision is that next generation COVID-19 vaccines may either be used to protect people who have not been vaccinated before, or to serve as boosters in the event that COVID-19 immunity gained from an initial vaccination reduces over time.

 

French biotech Valneva reported the UK government has exercised an option to order 40 million more doses of its COVID-19 vaccine for supply in 2022. This brings the total volume ordered by the UK to 100 million doses, with the UK government also holding options over a further 90 million doses for supply between 2023 and 2025.

The Nantes-based company is in advanced discussions with the European Commission for the supply of up to 60 million doses, but has yet to sign a formal advance purchase agreement to supply vaccine to the EU.

The total value of the 190 million UK doses, if all options are exercised, is up to €1.4 billion. Valneva announced last week that it has commenced production at its facility in near Edinburgh, in parallel with ongoing clinical trials, in order to optimise the timeline for potential deliveries of the vaccine. The phase I/II clinical study is now fully enrolled and is expected to read out within the next three months.

Thomas Lingelbach, CEO of Valneva said, “We are very pleased to extend our supply commitment to the UK. Assuming success, we believe that our vaccine, which has commenced commercial production at our site in Scotland, can make a major contribution to the UK’s vaccination efforts later this year as well as in 2022. This new development in our partnership underlines the need for our inactivated vaccine approach and we will continue to work closely with the Vaccines Task Force on execution.”
 

In the midst of acrimony over supplies to the EU, the European Medicines Agency has now granted a conditional marketing authorisation for the COVID-19 vaccine developed jointly by AstraZeneca and Oxford University.

EMA based its opinion on data from a rolling review of trial data from the primary analysis of the phase III clinical development programme led by Oxford University, which included 23,745 volunteers aged 18 years and older. Additional safety and efficacy data from ongoing clinical trials is expected to be published in the coming weeks.

AstraZeneca said it is working with the EU for vaccinations to begin across member states. Problems in scaling up the manufacturing process at facilities in Belgium and the Netherlands mean the company will deliver only 40 million of an expected 80 million doses by the end of March. The EU has ordered 300 million doses of the vaccine in total.

It is hard to get to the bottom of the legal position. The contract with AstraZeneca has been published by the European Commission, but it is redacted to the extent it is impossible to interpret key aspects.

Professor Andrew Pollard, director of the Oxford vaccine group and chief investigator on the Oxford vaccine trials, said, “The approval by the European Commission is an important milestone in extending access to the Oxford/AstraZeneca vaccine in our region.”

AstraZeneca is now seeking emergency use listing from the World Health Organisation for an accelerated pathway to make the vaccine available in low income countries. The company has said it will supply the vaccine at cost in all markets during the pandemic.

The vaccine can be stored, transported and handled at normal refrigerated conditions for at least six months and administered within existing healthcare settings.

 

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