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

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.

The European Commission has put in place what it calls a targeted “transparency and authorisation mechanism”, under which individual member states could stop COVID-19 vaccines being exported outside the EU.

The Commission said the move is an effort “to ensure timely access to COVID-19 vaccines for all EU citizens and to tackle the current lack of transparency of vaccine exports outside the EU.”

President of the European Commission Ursula von der Leyen said, “This transparency and authorisation mechanism is temporary, and we will of course continue to uphold our commitments towards low and middle income countries.”

The measure is limited to vaccines for which the EU has agreed advance purchase agreements, said executive vice president and Commissioner for trade Valdis Dombrovskis. “The aim is to provide greater clarity on vaccine production in the EU and their exports – this transparency has been lacking and is vital at this time.”

The Commission worked “for the best part of the last year” to get advance purchase agreements with vaccine producers, said Commissioner for health Stella Kyriakides. “We gave upfront funding to companies to build the necessary manufacturing capacity to produce vaccines, so deliveries can start as soon as they are authorised. We now need transparency on where the vaccines we secured are going and ensure that they reach our citizens.”

The restriction on export of COVID-19 vaccines outside the EU applies until the end of March 2021.

After delaying its COVID-19 vaccine development plan at the end of last year, French pharma Sanofi is now stepping in to help increase supplies of the Pfizer/BioNTech product that is currently the only vaccine available for use in the EU.

Sanofi will provide BioNTech access to its production infrastructure and from summer 2021 will do late stage manufacturing at its facility in Frankfurt to supply over 125 million doses of COVID-19 vaccine for the EU.

British national Paul Hudson, CEO of Sanofi said, “Although vaccination campaigns have started around the world, the ability to get shots into arms is being limited by lower than expected supplies and delayed approval timelines owing to production shortages. We have made the decision to support BioNTech and Pfizer in manufacturing their COVID-19 vaccine in order to help address global needs, given that we have the technology and facilities to do so.”

Sanofi will continue to develop its COVID-19 vaccine, after phase I/II study showed an immune response comparable to patients who recovered from COVID-19 in adults aged 18 to 49 years, but a low immune response in older adults likely due to an insufficient concentration of the antigen.

It plans to initiate a new phase II study in February, with support from the US Biomedical Advanced Research and Development Authority, to evaluate an improved antigen formulation in order to achieve high-level immune response across all age groups.

French biotech Valneva said it has commenced production of its COVID-19 vaccine candidate in Scotland, after signing a deal with the UK government in September last year.

Production has begun in parallel with the ongoing clinical trials, in order to speed the product to market, if the vaccine is found to be safe and effective.

In September 2020, Nantes-based Valneva announced a major COVID-19 vaccine partnership with the UK government for the supply of up to 190 million doses of its COVID-19 vaccine. If vaccine development is successful, Valneva will supply the UK with 60 million doses in the second half of 2021.

The company announced in January 2021 that it 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.

The phase I/II clinical study is now fully enrolled and is expected to report initial results in April 2021.

Thomas Lingelbach, CEO of Valneva, said, “Our team in Scotland have done an amazing job to get manufacturing started so quickly. I would like to thank the UK Vaccines Taskforce and the National Institute for Health Research who have played vital roles in the rapid recruitment and enrollment of the volunteers for the clinical study.”