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

Scientists at the Rega Institute at KU Leuven have developed a COVID-19 vaccine, RegaVax that requires only one dose and can be stored in normal fridges. That offers potential advantages over the COVID-19 vaccines arriving on the market first, which each require two doses - weeks apart - and some of which need to be stored in ultra-low temperature fridges.

RegaVax is based on an existing yellow fever vaccine that has been engineered to deliver the genetic code for the spike protein by which the SARS-CoV-2 invades human cells. The same vaccine has been used by the group at as the basis for vaccines against Zika virus, Ebola and rabies.

Preclinical results published this week in the science journal Nature show RegaVax protects hamsters from infection with SARS-CoV-2 after a single dose, and is also effective in monkeys.

"An inexpensive, single-dose vaccine that rapidly protects against infection, that can be stored and transported at fridge temperature, and that may, like the yellow fever vaccine on which it is based, result in long-lasting immunity, provides an important and much-needed diversification of the COVID-19 vaccine landscape," said Johan Neyts, who led the research.

The team is currently preparing for clinical trials and has formed a partnership with a manufacturer to produce the vaccine for these studies.

The UK health minister Matt Hancock said he expects the first batch of 800,000 doses of Pfizer/BioNTech’s COVID-19 vaccine to arrive in the country from Belgium in the next few days, after the UK Medicines & Healthcare products Regulatory Agency (MHRA) granted a temporary authorisation for its emergency use. This is the first emergency use authorisation anywhere, following a worldwide phase III trial of the vaccine.

Pfizer and BioNTech are anticipating further regulatory decisions across the globe in the coming days, with the European Medicines Agency having said its scientific committee for human medicines will conclude its assessment during an extraordinary meeting scheduled for 29 December at the latest. The European Commission will then fast track its decision making process with a view to granting a conditional marketing authorisation valid in all EU and EEA member states within days.

“We applaud the MHRA for [its] ability to conduct a careful assessment and take timely action to help protect the people of the UK,” said Albert Bourla, CEO of Pfizer. “As we anticipate further authorisations and approvals, we are focused on moving with the same level of urgency to safely supply a high quality vaccine around the world.”

The MHRA’s decision is based on a rolling submission, including data from the phase III clinical study, which demonstrated a vaccine efficacy rate of 95 per cent from 7 days after the second dose.

In July 2020, Pfizer and BioNTech announced an agreement with the UK to supply 30 million doses of the BNT162b2 mRNA-based vaccine, once authorised for emergency use. That agreement was increased to 40 million doses in early October. The delivery of the 40 million doses will occur throughout 2020 and 2021.

Based on current projections, Pfizer’s and BioNTech’s combined manufacturing network has the potential to supply globally up to 50 million vaccine doses in 2020 and up to 1.3 billion doses by the end of 2021.

Through its existing mRNA production sites in Mainz and Idar-Oberstein, Germany, BioNTech is able to produce mRNA for commercial supply and the company will increase its manufacturing capacity in 2021, once a third site in Germany starts up.

The vaccine needs to be stored at minus 80 degrees centigrade and Pfizer has established cold chain infrastructure to supply the vaccine worldwide, including distribution hubs that can store vaccine doses for up to six months. Frozen vials will be quickly shipped to designated points of vaccination, minimising the need for long term storage anywhere, and it is not expected the product will need to be stored at any location for more than 30 days.

German biotech BioNTech and partner Pfizer have submitted a formal application for conditional approval of their COVID-19 vaccine to the European Medicines Agency, completing the rolling review process initiated on 6 October. The companies said that if approved the vaccine will be available for use in Europe before the end of 2020.

The submitted data from the phase III trial demonstrated a vaccine efficacy rate of 95 per cent, from seven days after the second dose. Efficacy was consistent across age, gender, race and ethnicity demographics, with an observed efficacy in adults age 65 and over of more than 94 per cent. The vaccine, BNT162b2, also showed good tolerability with no safety concerns.

“We stand ready to ship COVID-19 vaccine doses as soon as potential authorisations will allow us,” said Pfizer CEO Albert Bourla.

In addition to submission to EMA, the US FDA and the UK Medicines and Healthcare products Regulatory Agency, the companies have initiated rolling submissions in Australia, Canada and Japan, and plan to submit applications to other regulatory agencies.

US biotech Novavax gave an update on its COVID-19 vaccine, NVX‑CoV2373, saying it completed enrollment of 15,000 participants in a pivotal phase III clinical trial being conducted in the UK.

Interim data are now expected as soon as early first quarter 2021, although the timing depends on the overall level of COVID-19 infections. In the week to 29 November, there was an average of 15,222 confirmed cases per day in the UK, though the level of infection is declining due to a four week lockdown, which comes to an end on 4 December.

Novavax said the phase III data are expected to form the basis to file for approval in the UK, EU and other countries. More than 25 percent of volunteers in the trial are over the age of 65, and a large proportion had underlying medical conditions.

Meanwhile, a phase IIb trial taking place in South Africa is also now fully enrolled. A total of 4,422 volunteers are taking part in the trial, which includes 245 people who are HIV-positive.

Novavax also expects to start a phase III clinical trial in the US and Mexico in the coming weeks and says more than 100 trial sites have been selected.

Vaccine material produced at commercial scale will be used in this study. Novavax was awarded $1.6 billion in funding from the US government’s Operation Warp Speed programme and the money is funding the US and Mexico phase III trial and manufacturing scale-up.

Moderna said it is today submitting its COVID-19 vaccine to the European Medicines Agency for conditional approval, after announcing new data from the phase III study of mRNA-1273.

The second analysis, conducted after 196 volunteers in the trial contracted COVID-19, confirms the efficacy observed at the first interim analysis and indicates vaccine efficacy of 94.1 per cent.

The company also announced it is asking for emergency use authorisation from the US Food and Drug Administration.

The phase III study enrolled more than 30,000 participants in the US. The primary endpoint is based on the number of confirmed COVID-19 cases, starting two weeks after the second dose of vaccine. Of the 196 cases in the latest analysis, 185 were in the placebo group, versus 11 cases in the mRNA-1273 group.  A secondary endpoint looked at severe cases of COVID-19, of which all 30 cases occurred in the placebo group. There was one COVID-19-related death, which occurred in the placebo group. 

Moderna said efficacy was consistent across age, race and ethnicity, and gender demographics. The 196 COVID-19 cases included 33 older adults, aged 65+, and 42 participants identifying as being from diverse communities. No new serious safety concerns have been identified.

EU leaders held a virtual meeting with Australian prime minister Scott Morrison today, in which they reconfirmed their resolve to work together to fight COVID-19, agreeing to strengthen bilateral research and innovation cooperation, and to share research data to combat the pandemic.

They also agreed to work together to ensure universal, equitable and early access to safe, effective and affordable COVID-19 vaccines, diagnostics and therapeutics. The EU and Australia have both committed funding to the almost €16 billion raised through the EU-led coronavirus global response pledging marathon.

Charles Michel, president of the European Council, the president of the European Commission, Ursula von der Leyen and Morrison, between them stressed the importance of continued international support for the Access to COVID-19 tools accelerator and the COVAX facility, which will make COVID-19 vaccines available to low income countries.

The leaders also agreed the EU and Australia will continue to work together to strengthen the World Health Organisation, and to improve global preparedness and response to health emergencies.

US biotech Moderna announced the European Commission has approved an agreement to secure 80 million doses of its COVID-19 vaccine mRNA-1273. 

Under the terms of the agreement, the commission has the option to increase its purchase from 80 million doses to a total of up to 160 million doses. The value of the contract was not disclosed.

The agreement will be finalised following a review by member states. Delivery of the vaccine could begin by the first quarter 2021 if it is approved for use by the European Medicines Agency, which started a rolling review of mRNA-1273 on November 17.  

In Europe, Moderna is working with partners Lonza of Switzerland and ROVI of Spain, for manufacturing and fill and finish outside the US. This is a dedicated supply chain to support Europe and countries other than the US. The company says it is on track to manufacture 500 million to 1 billion doses globally in 2021.

On November 16, Moderna announced that the independent data safety monitoring board for the phase III study said the trial had met the pre-specified statistical criteria and mRNA-1273 has efficacy of 94.5 per cent.

The second interim analysis of the phase III clinical trial data of the Russian COVID-19 vaccine Sputnik V, showed it is 91.4 per cent effective.

The calculation was based on the analysis of data on 18,794 volunteers who received both the first and second doses of the Sputnik V (the V stands for vaccine) or placebo, at the second control point, of 39 confirmed cases of COVID-19 infection as of November 23, 2020.

That analysis was made seven days after volunteers received the second dose of the vaccine. Preliminary data from volunteers 21 days after the second dose indicates efficacy is above 95 per cent.

The Russian Direct Investment Fund, the sovereign wealth fund that is funding development of the vaccine, said the cost in international markets will be less than US$10 per dose for the two dose vaccine. The fund currently has agreements in place with foreign pharmaceutical companies to manufacture 1 billion doses and is assessing other applications to further increase production capacity. The vaccine will be free for Russian citizens.

Currently, 40,000 volunteers are taking part in the phase III double-blind, randomised, placebo-controlled clinical post-registration study of the Sputnik V vaccine in Russia. There were no unexpected adverse events and monitoring of the participants is ongoing.

Sputnik V is based on a human adenoviral vector platform that has proven safe and effective with no long-term side effects in more than 250 clinical trials globally conducted during the past two decades. More than 100,000 people have received approved and registered drugs that use inactivated human adenoviruses, which cause the common cold, as the therapeutic delivery vehicle.

The interim analysis of the phase III interim trial of AstraZeneca/Oxford University’s COVID-19 vaccine, conducted after 131 people in the trial contracted the infection, shows it is 70.4 per cent effective when combining data from two dosing regimens. In the two different regimens vaccine efficacy was 90 per cent in one, when the immune system was primed with a half dose, followed by a full dose, compared to 62 per cent in those receiving two full doses.

There early signs that the vaccine could reduce virus transmission and serious disease,  with no hospitalised or severe cases in anyone who received the vaccine.

AstraZeneca and the researchers at Oxford University are stressing a critical attribute of their vaccine, which is that it can be easily administered in existing healthcare systems, being stored at fridge temperature of 2-8 °C and distributed using existing logistics.

Large scale manufacturing is ongoing in over 10 countries to support equitable global access, and AstraZeneca said the safety and efficacy data will now be submitted to the European Medicines Agency, the UK Medicines and Healthcare products Agency and other regulators for approval.

Andrew Pollard, director of the Oxford vaccine group and chief investigator of the Oxford trial, said, “These findings show that we have an effective vaccine that will save many lives. Excitingly, we’ve found that one of our dosing regimens may be around 90 per cent effective and if this dosing regime is used, more people could be vaccinated with planned vaccine supply.”

The AstraZeneca/Oxford University COVID-19 vaccine shows similar safety and strength of immune response in people aged 56 years and over to that seen in adults aged 18-55 years, according to phase II results published today in The Lancet.

The phase II trial found the vaccine causes few side effects, and induces immune responses in both parts of the immune system in all age groups and at low and standard dose, provoking a T cell response within 14 days of the first dose and an antibody response within 28 days of the booster dose of vaccination. Phase III trials are ongoing to confirm these results - as well as how effective the vaccine is in protecting against COVID-19 infection – in a broader range of people, including older adults with underlying health conditions.

The study is the fifth published clinical trial of a vaccine against COVID-19 tested in an older adult population. One study has shown similar immune responses in young and old adults (Moderna mRNA vaccine), while other trials have suggested lower responses in older adults, compared to younger adults receiving the same vaccine (CanSino single dose adenovirus-vector vaccine; Pfizer/BioNTech mRNA vaccine; and SinoPharm/Beijing Institute of Biological Products inactivated viral vaccine).